Complexing agent salt formulations of pharmaceutical compounds at low stoichiometric ratios

Abstract

Provided herein are pharmaceutical formulations and pharmaceutical compound salts which utilize complexing agents as counterions. Such formulations and salts are useful for treating a variety of disease and disorders. Provided herein are also treatment methods using the pharmaceutical compounds, pharmaceutical compositions, and pharmaceutically acceptable salts of the present disclosure.

Description

Attorney Docket No.: 53160-716.601 COMPLEXING AGENT SALT FORMULATIONS OF PHARMACEUTICAL COMPOUNDS AT LOW STOICHIOMETRIC RATIOS CROSS REFERENCE(S) TO OTHER APPLICATIONS

[0001] This application claims the benefit of U.S. provisional application no.63 / 602,269, filed November 22, 2023, the entirety of which is incorporated by reference herein. BACKGROUND

[0002] Pharmaceutical compounds and their derivatives, such as rotigotine, eletriptan, DXM, midazolam, copanlisib, remdesivir, melevodopa, tigecycline, naloxone, amikacin, 1-amantadine, 2-amantadine, rimantadine, amifampridine, rapamycin, clonidine, or caspofungin, are useful for a variety of medicinal purposes. These compounds can be used to treat, for example, Parkinson's disease, migraine, cancer, viral infection, bacterial infection, autoimmune disease, inflammatory disease, opioid dependence, pain, or other disorders. However, the compounds may possess many physico-chemical properties that make suitable formulations for widespread use as pharmaceutical agents difficult, including the presence of basic amines, limited solubility, hydrophobicity, and inherently ionic functional groups. BRIEF SUMMARY

[0003] In some aspects, provided herein are pharmaceutical compositions comprising: (i) a pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof, wherein the pharmaceutical compound comprises a protonated nitrogen atom and has a pKa of about 1 to about 7.5; and (ii) a complexing agent, wherein the complexing agent is an acid-substituted cyclodextrin comprising a plurality of acidic functional groups comprising an acidic group which acts as a counterion for the protonated nitrogen atom of the pharmaceutical compound, wherein the pharmaceutical composition has a molar ratio of the complexing agent to the pharmaceutical compound that is from about 1:1 to about 1:10. In some aspects, provided herein are pharmaceutical compositions comprising (i) a pharmaceutical compound, an enantiomer, or an isotopic variant thereof, wherein the pharmaceutical compound comprises a protonated nitrogen atom and has a pKa of at least 1; and (ii) a complexing agent, wherein the complexing agent is an acid-substituted cyclodextrin comprising a plurality of acidic functional groups comprising an acidic group which acts as a counterion for the protonated nitrogen atom of the pharmaceutical compound, wherein the pharmaceutical composition has a molar ratio of the complexing agent to the pharmaceutical compound that is from about 1:1 to about 1:10. In some aspects, provided herein are pharmaceutical compositions, comprising (i) a pharmaceuticalAttorney Docket No.: 53160-716.601 compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof, wherein the pharmaceutical compound comprises a protonated nitrogen atom and has a pKa of about 1 toabout 13; and (ii) a complexing agent, wherein the complexing agent is an acid -substitutedcyclodextrin comprising a plurality of acidic functional groups comprising an acidic group which acts as a counterion for the protonated nitrogen atom of the pharmaceutical compound, wherein the pharmaceutical composition has a molar ratio of the complexing agent to the pharmaceutical compound that is from about 1:1 to about 1:10. In some aspects, provided herein are pharmaceutical compositions comprising: (i) a pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof, wherein the pharmaceutical compound comprises a protonated nitrogen atom and has a pKa of about 4 to about 13; and (ii) a complexing agent, wherein the complexing agent is an acid-substituted cyclodextrin comprising a plurality of acidic functional groups comprising an acidic group which acts as a counterion for the protonated nitrogen atom of the pharmaceutical compound, wherein the pharmaceutical composition has a molar ratio of the complexing agent to the pharmaceutical compound that is from about 1:1 to about 1:10. In some embodiments, the complexing agent comprises a substituted cyclodextrin. In some embodiments, the complexing agent comprises a cyclodextrin substituted with at least one acidic functional group. In some embodiments, the cyclodextrin is substituted with 3 to 8 acidic functional groups. In some embodiments, the cyclodextrin is sulfobutylether-β-cyclodextrin (SBEBCD). In some embodiments, the pharmaceutical compound has a pKa of at least 1. In some embodiments, the pharmaceutical compound has a pKa of about 1 to about 7.5. In some embodiments, the pharmaceutical compound has a pKa of about 1 to about 5. In some embodiments, the pharmaceutical compound has a pKa of about 7.5to about 13. In some embodiments, the pharmaceutical compound comprises 5' -deoxyribonucleosides, 6,7-benzomorphans, ajmaline-sarpagine alkaloids, alkaline earth metal organides, amaryllidaceae alkaloids, anthracenes, anthracyclines, aporphines, azaspirodecane, azepanes, azobenzenes, azoles, azolidines, azolines, benzazepines, benzene and substituted, benzimidazole ribonucleosides and ribonucleotides, benzimidazoles, benzocycloheptapyridines, benzodiazepines, benzodioxanes, benzodioxoles, benzofurans, benzopyrans, benzopyrazoles,benzothiadiazoles, benzothiazepines, benzothiazines, benzothiazoles, benzoth iepins,benzothiophenes, benzothiopyrans, benzotriazoles, benzoxadiazoles, benzoxazepines, benzoxazines, benzoxepines, biotin, camptothecins, carboxylic acids, cephalotaxus alkaloids, cinchona alkaloids, cinnamic acids, coumarans, cycloheptathiophenes, depsides and depsidones, diarylheptanoids, diazanaphthalenes, diazinanes, diazines, dibenzocycloheptenes, dioxanes, epoxides, ergoline, fatty acyls, flavin nucleotides, flavonoids, fluorenes, furans, furopyrans,Attorney Docket No.: 53160-716.601 glycerophospholipids, homogeneous other non-metal compounds, hydroxy acids, ibogan-type alkaloids, imidazodiazepines, imidazole ribonucleosides and ribonucleotides, imidazopyridines, imidazopyrimidines, imidazothiazoles, indanes, indenes and isoindenes, indoles, indolizidines, isocoumarans, isoindoles, isoquinolines, lactams, linear 1,3-diarylpropanoids, lupin alkaloids, macrolactams, macrolide lactams, macrolides morphinans, naphthacenes, naphthalenes, naphthofurans, naphthopyrans, nucleoside and nucleotide analogues, organic carbonic acids, organic phosphines, organic phosphonic acids, organic sulfonic acids, organonitrogen compounds, organooxygen compounds, organothiophosphorus compounds, oxazinanes, peptidomimetics, phenanthrenes, phenanthrolines, phenol esters, phenol ethers, phenols, phenylpropanoic acids, phthalide isoquinolines, piperazinoazepines, piperidines, polypeptides, prenol lipids, pteridines, purine nucleosides, purine nucleotides, pyrazolopyridines, pyrazolopyrimidines, pyridines, pyridopyrimidines, pyrimidine nucleosides, pyrroles, pyrrolidines, pyrrolopyrazines, pyrrolopyridines, pyrrolopyrimidines, quinolines, steroids and steroid, stilbenes, tetracyclines, tetrahydroisoquinolines, tetralins, thiadiazines, thienodiazepines, thienopyridines, thienothiazines, thiochromenes, thioethers, thiols, thiophenes, transition metal salts, triazinanes, triazines, triazole ribonucleosides and ribonucleotides, triazolopyrimidines, triphenyl compounds, tropane alkaloids, vinca alkaloids, yohimbine alkaloids, or a derivative thereof, or a combination thereof. In some embodiments, the pharmaceutical compound has a pKa of about 1 to about 2. In some embodiments, the pharmaceutical compound comprises a 1,4-benzodiazepine, amine, amino acid, peptide, androstane steroid, benzenesulfonamide, benzoic acids, benzophenone, benzothiadiazine, biphenyls, carboxylic acid derivative, depsipeptide, diphenylmethane, ether, halobenzene, isoindoline, nitrogen mustard compound, nitroquinolines, purine 2’-deoxyribonucleoside, purines, pyrazole, pyrimidines or derivative thereof, retinoid, substituted pyrrole, or a combination thereof. In some embodiments, the pharmaceutical compound comprises apadenoson, asunaprevir, azilsartan medoxomil,benzthiazide, bromfenac, candesartan cilexetil, carbazochrome, chlorambucil, chlorothiaz ide,cladribine, clofarabine, clonazepam, CVT-6883, CX516, dacarbazine, diazoxide, emodepside, fimasartan, flubendazole, flucytosine, fludiazepam, flunitrazepam, ganciclovir, gliclazide, glisoxepide, grazoprevir, guanosine, ibudilast, ibuproxam, iocetamic acid, iopamidol, iopanoic acid, isatoribine, ixazomib, MB-07803, nateglinide, nepafenac, OPC-51803, pleconaril, pomalidomide, pralnacasan, pyrvinium, regadenoson, rimonabant, selexipag, simeprevir, sulfadimethoxine, sulfamerazine, sulfameter, sulfamethizole, sulfamethoxazole, sulfametopyrazine, sulfamoxole, taranabant, tazarotene, tiopronin, tolazamide, trapidil, uracil mustard, or a combination thereof. In some embodiments, the pharmaceutical compound has aAttorney Docket No.: 53160-716.601 pKa of about 2 to about 3. In some embodiments, the pharmaceutical compound comprises azobenzene, azole, benzazepine, benzene, benzodiazepine, benzothiazine, benzothiazole, carboxylic acid, depside, diazanaphthalene, diazine, imidazopyrimidine, indole, isoindole, lactam, macrolides naphthalene, nucleoside and nucleotide analogue, organooxygen compound, piperidine, prenol lipid, pteridine, purine nucleoside, purine nucleotide, pyrazolopyrimidine, pyridine, pyrimidine nucleoside, pyrrolopyridine, quinoline, steroid, thienodiazepine, triazine, triazolopyrimidine, or a combination thereof. In some embodiments, the pharmaceutical compound comprises 1,4-benzodiazepines, amino acids or peptides, aminotriazines, androstane steroids, anilides, aniline and substituted anilines, benzazepines, benzenesulfonamides, benzenesulfonyl compounds, benzodiazines, benzoic acids and derivatives, beta lactams, biphenyls and derivatives, carbazoles, diphenylethers, diphenylmethanes, epothilones estrane steroids, ethers, halobenzenes, isoindolines, milbemycins, monoterpenoids, nitroquinolines and derivatives, oxosteroids, phenoxyacetic acid derivatives, phenylbutylamines, phenylcarbamic acid esters, phenylmethylamines, phenylpropanes, phenylquinolines, pterins and derivatives, purine 2',3'-dideoxyribonucleosides, purine ribonucleotides, purines and purine derivatives, pyrazoles, pyrazolo[3,4-d]pyrimidines, pyridinecarboxylic acids and derivatives, pyrimidines and pyrimidine derivatives, sulfanilides, or a combination thereof. In some embodiments, the pharmaceutical compound comprises aciclovir, adipiplon, alisertib, allopurinol, ambrisentan, amelubant, aminobenzoic acid, aminopterin, aminosalicylic acid, amprenavir, anastrozole, arsanilic acid, asoprisnil, benzocaine, BMS-488043, brecanavir, bromazepam, bumetanide, butamben, cangrelor, cefixime, cefpiramide, chromium picolinate, cidofovir, ciluprevir, cinalukast, clazosentan, clotiazepam, cloxazolam, dabrafenib, dapsone, darunavir, delorazepam, diazepam, didanosine, dutasteride, edotecarin, efonidipine, elacytarabine, entecavir, epirizole, epothilone d, finasteride, fluconazole, flutemetamol (18F), folic acid, fomepizole, fosamprenavir, ganstigmine, GW-501516, halazepam, indocyanine green, inosine, iodamide, iopromide, isavuconazole, ixabepilone, KOS-1584, KP-1461, lenalidomide, letrozole, leucovorin, levoleucovorin, macitentan, meradimate, mercaptopurine, methotrexate, methylene blue, methylthioninium, motexafin gadolinium, motexafin lutetium, moxidectin, naxifylline, nitrazepam, nitroxoline, olaparib, ombitasvir, OT-551, padimate O, paritaprevir, patupilone, penciclovir, phenyl aminosalicylate, PPL-100, pralatrexate, quazepam, ravuconazole, regorafenib, regrelor, ritonavir, roflumilast, roxadustat, silver sulfadiazine, sorafenib, stanozolol, sulfabenzamide, sulfacetamide, sulfacytine, sulfadiazine, sulfadoxine, sulfamerazine, sulfamethazine, sulfanilamide, sulfaphenazole, sulfapyridine, sulfasalazine, sulfathiazole, sulfisoxazole, talnetant, tasosartan, technetium tc-99m disofenin, technetium tc-99mAttorney Docket No.: 53160-716.601 mebrofenin, tezosentan, ticagrelor, tirapazamine, troxacitabine, trypan blue, voriconazole, or a combination thereof. In some embodiments, the pharmaceutical compound has a pKa of about 3to about 4. In some embodiments, the pharmaceutical compound comprises a 1,4 -benzodiazepine, amino acid, peptide, anilide, aniline and substituted aniline, anisole, aryl thioether, benzodiazine, benzofuranone, benzoic acids and derivative, benzophenone, beta lactam, biphenyls and derivative, bipyridines and oligopyridine, carbodiimide, diphenylether, diphenylmethane, epothilones estrane steroid, ether, haloquinoline, hexacarboxylic acids and derivative, imidazole, isoindole, milbemycin, morpholine, phenoxyacetic acid derivative,phenylmethylamine, phenylpyridine, piperazine, pterins and derivative, purine 2’,3’ -dideoxyribonucleoside, purines and purine derivative, purines and purine derivative, pyrazine, pyrazole, pyridine carboxaldehyde, pyridinecarboxylic acids and derivative, pyridinesulfonamide, pyridyltriazole, steroid ester, sulfanilide, sulfinylbenzimidazole, or a combination thereof. In some embodiments, the pharmaceutical compound comprises adenosine, amiloride, aminobenzoic acid, aminophenazone, anagrelide, aprepitant, arsanilic acid, azathioprine, aztreonam, benzocaine, benzonatate, bisacodyl, bromazepam, brotizolam, bumetanide, butamben, calcium carbimide, cefepime, cefixime, cefmenoxime, cefotaxime, cefpodoxime, ceftizoxime, ceftriaxone, chloroxine, chromium picolinate, clioquinol, dabigatran etexilate, dabrafenib, dexlansoprazole, dexrazoxane, diazepam, didanosine, diiodohydroxyquinoline, entecavir, etofibrate, etravirine, ezogabine, flumazenil, flutemetamol (18F), indocyanine, inosine, inositol nicotinate, iopodic acid, irbesartan, isocarboxazid, isocarboxazid, isoniazid, itraconazole, ixabepilone, lansoprazole, leucovorin, levoleucovorin, levomefolic acid, lobeglitazone, losartan, lumacaftor, mazindol, mebendazole, mercaptopurine, mercaptopurine, methotrexate, metronidazole, metronidazole, montelukast, montelukast, moxidectin, nelarabine, niacin, nicorandil, nicotinamide, norelgestromin, norgestimate, oxfendazole, padimate o, pantoprazole, penciclovir, perampanel, picosulfuric acid, piroxicam, posaconazole, pralatrexate, prazepam, procaine merethoxylline, pyridoxal, pyridoxal phosphate, riociguat, ritonavir, stanozolol, talniflumate, tasosartan, tenofovir disoproxil, thiabendazole, thonzonium, ticagrelor, tinidazole, tioguanine, topiroxostat, torasemide, triamterene, triamterene, vemurafenib, vemurafenib, vismodegib, or a combination thereof. In some embodiments, the pharmaceutical compound has a pKa of about 4 to about 5. In some embodiments, the pharmaceutical compound comprises 1,4-benzodiazepine, 1-ribosyl-imidazolecarboxamide, 2- benzimidazolylcarbamic acid ester, 8-hydroxyquinoline, amine, amino acid, peptide, androstane steroid, anilide, aniline and substituted aniline, anthraquinone, aryl thioether, benzodiazine, benzoic acids and derivative, beta lactam, biphenyls and derivative, bipyridines andAttorney Docket No.: 53160-716.601 oligopyridine, bisphosphonate, carbonyl compound, diphenylmethane, ether, hexacarboxylic acids and derivative, imidazole, imidazoquinoline, indolequinone, naphthyridine, oxosteroid, phenethylamine, phenylbenzimidazole, phenylhydrazine, phenylpiperidine, phenylpyridine, phenylquinoline, pterins and derivative, purine ribonucleotide, purines and purine derivative, pyrazolo[1,5-a]pyrimidine, pyridine carboxaldehyde, pyridinecarboxylic acids and derivative, pyridinesulfonamide, pyridoindole, quinoline carboxylic acid, styrene, sulfinylbenzimidazole, trifluoromethylbenzene, or a combination thereof. In some embodiments, the pharmaceuticalcompound comprises azathioprine, abiraterone, acadesine, adenosine 5' -phosphosulfate,adenosine monophosphate, AICA ribonucleotide, albendazole, amfecloral, aminoglutethimide, aminohippuric acid, amrinone, atazanavir, aztreonam, banoxantrone, binodenoson, bisacodyl, carfilzomib, cefditoren, cefepime, cefmenoxime, cefotaxime, cefpodoxime, ceftazidime,ceftibuten, ceftizoxime, ceftriaxone, coenzyme A, dexlansoprazole, ensulizole, e rlotinib,esomeprazole, estazolam, etizolam, etomidate, etoricoxib, etravirine, fiboflapon, flavin adenine dinucleotide, florbetaben (18F), florbetapir (18F), geldanamycin, gentian violet, hexocyclium, idelalisib, implitapide, indium In-111 oxyquinoline, inositol nicotinate, iopodic acid, irbesartan, lansoprazole, levosimendan, loratadine, lornoxicam, losartan, LX-2931, methoxyamine, metyrapone, mifepristone, milrinone, minoxidil, nalidixic acid, niacin, ocinaplon, omeprazole, OSI-930, oxibendazole, oxyquinoline, perampanel, piclidenoson, picosulfuric acid, pitavastatin, porfiromycin, PX-12, pyridoxal, pyridoxal phosphate, rabeprazole, repaglinide, resiquimod, retaspimycin, ridogrel, riluzole, risedronate, rivoglitazone, rosoxacin, S-8510, sapropterin, tecadenoson, tenofovir disoproxil, tenoxicam, thiabendazole, torasemide, triazolam, tucidinostat, ulipristal, varlitinib, vatalanib, verteporfin, verubulin, vidarabine, vipadenant, vorapaxar, or a combination thereof. In some embodiments, the pharmaceutical compound has a pKa of about 5to about 6. In some embodiments, the pharmaceutical compound comprises a 1,4 -benzodiazepine, 1-ribosyl-imidazolecarboxamide, 2-benzimidazolylcarbamic acid ester, 8-hydroxyquinoline, amine, amino acid, peptide, androstane steroid, anilide, aniline andsubstituted aniline, anthraquinone, aryl thioether, benzodiazine, benzoic acid, beta lactam, biphenyl, bipyridines and oligopyridine, bisphosphonate, diphenylmethane, ether, hexacarboxylic acid, imidazole, imidazoquinoline, indolequinone, naphthyridine, oxosteroid, phenethylamine, phenylbenzimidazole, phenylhydrazine, phenylpiperidine, phenylpyridine,phenylquinoline, pterin, purine ribonucleotide, purines and purine derivative, pyrazolo[1,5 -a]pyrimidine, pyridine carboxaldehyde, pyridinecarboxylic acid, pyridinesulfonamide, pyridoindole, quinoline carboxylic acid, styrene, sulfinylbenzimidazole, trifluoromethylbenzene, or a derivative thereof, or a combination thereof. In some embodiments, the pharmaceuticalAttorney Docket No.: 53160-716.601 compound comprises 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, 5- methyltetrahydrofolic acid, abacavir, adefovir dipivoxil, adenine, alprazolam, ALT-2074, amdoxovir, apilimod, adenosine triphosphate, avanafil, axitinib, azelnidipine, benazepril, benzimidazole, bicisate, biricodar dicitrate, brilliant green, cabozantinib, capravirine, carbidopa, cefapirin, cerivastatin, cilazapril, cisplatin, clevidipine, clonixin, clopidogrel, cocarboxylase, dapivirine, delamanid, dersalazine, dolasetron, elbasvir, enalapril, ethionamide, etifoxine, etozoline, famciclovir, felodipine, floctafenine, fominoben, fosaprepitant, GTS-21, hetacillin, imidacloprid, imiquimod, incadronic acid, indibulin, isosulfan blue, isradipine, kinetin, lamotrigine, ledipasvir, linsitinib, meclinertant, mesalazine, methenamine, moexipril, morniflumate, NADH, nevirapine, nifedipine, niflumic acid, nimodipine, nisoldipine, nitrendipine, olmesartan, pazopanib, peldesine, perindopril, phenelzine, picoplatin, pinacidil, pioglitazone, pipecuronium, pradefovir mesylate, prasugrel, prinomastat, procarbazine, pyridoxine, quinapril, ramipril, rilpivirine, rostaporfin, ruxolitinib, seliciclib, sildenafil, sonidegib, spirapril, stannsoporfin, talmapimod, taribavirin, temocapril, temoporfin, tenofovir alafenamide, thiamine, trandolapril, tropicamide, velpatasvir, ximelagatran, zinc picolinate, zolpidem, or a combination thereof. In some embodiments, the pharmaceutical compound has apKa of about 6 to about 7. In some embodiments, the pharmaceutical compound comprises 1,4 -benzodiazepine, 1-ribosyl-imidazolecarboxamide, 2-benzimidazolylcarbamic acid ester, 8- hydroxyquinoline, amine, amino acid, peptide, androstane steroid, anilide, aniline and substituted aniline, anthraquinone, aryl thioether, benzodiazine, benzoic acid, beta lactam, biphenyl, bipyridines and oligopyridine, bisphosphonate, carbonyl compound, diphenylmethane, ether, hexacarboxylic acid, imidazole, imidazoquinoline, indolequinone, naphthyridine, oxosteroid, phenethylamine, phenylbenzimidazole, phenylhydrazine, phenylpiperidine, phenylpyridine, phenylquinoline, pterin, purine ribonucleotide, purines and purine derivative, pyrazolo[1,5-a]pyrimidine, pyridine carboxaldehyde, pyridinecarboxylic acid,pyridinesulfonamide, pyridoindole, quinoline carboxylic acid, styrene, sulfiny lbenzimidazole,trifluoromethylbenzene, or a derivative thereof, or a combination thereof. In some embodiments, the pharmaceutical compound comprises 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, 5- methyltetrahydrofolic acid, abacavir, adefovir dipivoxil, adenine, alprazolam, ALT-2074, amdoxovir, apilimod, avanafil, azelnidipine, benazepril, benzimidazole, bicisate, biricodar dicitrate, brilliant green, capravirine, carbidopa, cerivastatin, cilazapril, cisplatin, clevidipine, clonixin, clopidogrel, cocarboxylase, dapivirine, delamanid, dersalazine, dolasetron, elbasvir, enalapril, etifoxine, etozoline, famciclovir, felodipine, floctafenine, fominoben, fosaprepitant, GTS-21, hetacillin, imidacloprid, imiquimod, incadronic acid, indibulin, isosulfan blue,Attorney Docket No.: 53160-716.601 isradipine, kinetin, lamotrigine, ledipasvir, meclinertant, mesalazine, methenamine, moexipril, morniflumate, nevirapine, nifedipine, niflumic acid, nimodipine, nisoldipine, nitrendipine,olmesartan, pazopanib, peldesine, perindopril, phenelzine, picoplatin , pinacidil, pioglitazone,pipecuronium, pradefovir mesylate, prasugrel, prinomastat, procarbazine, pyridoxine, quinapril, ramipril, rilpivirine, rostaporfin, ruxolitinib, seliciclib, sildenafil, sonidegib, spirapril, stannsoporfin, talmapimod, taribavirin, temocapril, temoporfin, tenofovir alafenamide, thiamine, trandolapril, tropicamide, velpatasvir, ximelagatran, zinc picolinate, zolpidem, acarbose, ajmaline, alcaftadine, alfentanil, alfuzosin, almitrine, amisulpride, amoxicillin, ampicillin, amrubicin, antrafenine, aripiprazole, asenapine, atipamezole, azaperone, bacampicillin, cefaclor, cefadroxil, cefdinir, cefprozil, cephalexin, cephaloglycin, chlordiazepoxide, clozapine,dalfopristin, dasatinib, diethylpropion, domperidone, dorzolamide, doxapram, dox azosin,drotaverine, efinaconazole, eprazinone, flavoxate, flibanserin, flupirtine, imidafenacin, indinavir, ketamine, ketotifen, lapatinib, loxapine, mepivacaine, methacycline, moxonidine, nefazodone, oftasceine, olanzapine, ondansetron, phendimetrazine, pivampicillin, pramocaine, prazosin, quetiapine, ranolazine, rupatadine, setiptiline, terazosin, tetrabenazine, ticlopidine, tizanidine, tofacitinib, trazodone, trimethoprim, valaciclovir, valganciclovir, ziprasidone, or a combination thereof. In some embodiment the pharmaceutical compound has a pKa of about 7 to about 8. In some embodiments, the pharmaceutical compound comprises an ajmaline-sarpagine alkaloid, 1,4-benzodiazepine, 2,3,5-trisubstituted thiophene, alcohols and polyol, amine, amino acid or peptide, anilide, anisole, benzazepine, benzazocine, benzene, benzimidazole, benzocycloheptapyridine, benzodiazepine, benzodiazine, benzofuran, benzoic acid, benzothiadiazole, benzothiazepine, benzotriazole, benzoxazepine, benzoxepine, benzylamine, benzylisoquinoline, benzylpiperidine, beta lactam, biphenyl, carbazole, carbohydrate, carbonyl compound, carboxylic acid, cycloheptathiophene, diarylheptanoid, diazanaphthalene, diazinane, diazine, dibenzocycloheptene, dibenzodiazepine, dibenzothiazepine, dibenzoxazepine, dibenzoxepine, diphenylmethane, ergolin, flavone, flavonoid, halobenzene, hybrid peptide, hydropyridine, indane, indole, indoline, isoquinoline, isoquinolone, lactam, linear diarylheptanoid, lysergic acid, macrolactam, macrolide lactam, monoterpenoid, morpholine, n-acylpiperidine, n-alkylindole, naphthacene, naphthopyranone, naphthopyran, n -phenylurea,organonitrogen compound, organooxygen compound, oxazinane, pentacarboxylic acid, peptidomimetic, phenanthrene, phenethylamine, phenol ether, phenylmethylamine, phenylpiperidine, phenyltropane, piperazine, piperidinecarboxylic acid, piperidine, polypeptide,prenol lipid, pyridazines and derivative, pyridine, pyrimidine 2' -deoxyribonucleoside,pyrimidine nucleoside, pyrimidine, quinoline carboxylic acid, quinoline, steroid ester, steroid,Attorney Docket No.: 53160-716.601 tetracenequinone, tetracycline, tetrahydroisoquinoline, thienopyridine, thiophene, tropane alkaloid, xylene, yohimbine alkaloid, or derivatives thereof, or a combination thereof. In some embodiments, the pharmaceutical compound comprises acarbose, ajmaline, alcaftadine, alfentanil, alfuzosin, alizapride, almitrine, almorexant, altretamine, altropane, alvocidib, amdinocillin, aminolevulinic acid, amisulpride, amoxicillin, ampicillin, amrubicin, antrafenine, aripiprazole, asenapine, atipamezole, AV-412, azaperone, azatadine, bacampicillin, barnidipine, benidipine, bifeprunox, bleomycin, blonanserin, bradanicline, brifentanil, bupivacaine, buspirone, cariporide, cariprazine, casopitant, cathinone, cefaclor, cefadroxil, cefdinir, cefprozil, cefradine, cephalexin, cephaloglycin, cethromycin, cetirizine, chlorcyclizine, chlordiazepoxide, chlortetracycline, cilansetron, clozapine, dalfopristin, dapiprazole, dasatinib, deserpidine, diethylpropion, domperidone, dorzolamide, dovitinib, doxapram, doxazosin, doxycycline, drotaverine, edonerpic, efinaconazole, elsamitrucin, eluxadoline, enalaprilat, enzastaurin, eprazinone, ergonovine, ergotamine, EVT-101, ezatiostat, facinicline, fenproporex, finafloxacin, flavoxate, flibanserin, flunarizine, flupirtine, hexaminolevulinate, hydroxyzine, iclaprim, iloperidone, imidafenacin, indinavir, josamycin, ketamine, ketotifen, lapatinib, larazotide, lesopitron, levobupivacaine, levocetirizine, lidocaine, linaclotide, lofexidine, loracarbef, lorpiprazole, loxapine, lysergic acid diethylamide, manidipine, mepiprazole, mepivacaine, methacycline, methyl aminolevulinate, methylergometrine, methysergide, miglitol, motesanib,moxonidine, naloxone, naluzotan, nefazodone, netupitant, oftasceine, olanzapine, on alespib,ondansetron, oxytetracycline, palonosetron, perospirone, phendimetrazine, phenoxybenzamine,pirenzepine, pivampicillin, pivmecillinam, pizotifen, pramocaine, prazosin, priralfinamide, prx -08066, pyrimethamine, quetiapine, RAF-265, raloxifene, ranolazine, reboxetine, remifentanil, rescinnamine, reserpine, rifampicin, rifapentine, rocuronium, ropivacaine, rupatadine, safinamide, saxagliptin, setiptiline, SNX-5422, solithromycin, sufugolix, SUVN-502, talactoferrin alpha, telithromycin, terazosin, tetrabenazine, ticlopidine, tipifarnib, tizanidine, tofacitinib, trabectedin, trazodone, trimethoprim, trimetrexate, tymazoline, valaciclovir, valganciclovir, valomaciclovir, valtorcitabine, venetoclax, voglibose, yohimbine, ziprasidone, zosuquidar, or a combination thereof. In some embodiments, the pharmaceutical compound hasa pKa of about 8 to about 9. In some embodiments, the pharmaceutical compound comprises 1 -benzopyran, 1-benzothiopyran, 1-phenyltetrahydroisoquinoline, alcohol, polyol, amine, amino acid, peptide, aminoquinoline and derivative, androstane steroid, anilide, anisole, aryl thioether, benzenediol, benzenesulfonamide, benzo-1,4-dioxane, benzodiazine, benzoic acid and derivative, benzoquinoline, benzylamine, benzylether, benzylpiperidine, beta lactam, biphenyl and derivative, carbazole, carbohydrate and carbohydrate conjugate, carbonyl compound,Attorney Docket No.: 53160-716.601 carboxylic acid derivative, depsipeptide, dibenzazepine, dibenzothiepin, dibenzoxazepine, diphenylacetonitrile, diphenylfuran, diphenylmethane, ether, fatty acid and conjugate, fentanyl, galanthamine-type amaryllidaceae alkaloid, halobenzene, hydropyridine, imidazolidine, indazole, indole, indoloquinoline, isoquinolone and derivative, isoxazoline, lysergic acid and derivative, methoxybenzene, monoterpenoid, morpholine, n-alkylindole, naphthyridine, oxadiazole, pentacarboxylic acid and derivative, phenethylamine, phenothiazine, phenoxazine, phenoxy compound, phenylmethylamine, phenylnaphthalene, phenylpiperidine, phenylpropane, phenylpyridine, phenylpyrrolidine, phenylquinoline, piperazine, piperidinecarboxylic acid and derivative, purine and purine derivative, pyrimidine and pyrimidine derivative, pyrrolidinylpyridine, quinoline carboxamide, quinoline carboxylic acid, styrene, substituted pyrrole, sulfanilide, tetracarboxylic acid and derivative, thiazole, thiophene carboxylic acid and derivative, trifluoromethylbenzene, xylene, or a derivative thereof, or a combination thereof. In some embodiments, the pharmaceutical compound comprises aceprometazine, acetophenazine,aclarubicin, acrivastine, afatinib, afimoxifene, alanosine, amiodarone, ammonia n -13,ammonium molybdate, amonafide, amorolfine, amoxapine, amsacrine, amylocaine, anamorelin, anileridine, aplindore, apraclonidine, articaine, arzoxifene, asimadoline, aspartame, astemizole, atrasentan, azelastine, azimilide, bedaquiline, benzylfentanyl, bosutinib, brexpiprazole, brimonidine, bromodiphenhydramine, buclizine, budiodarone, bupivacaine, bupropion, butyrfentanyl, caldaret, captodiame, carbinoxamine, carfentanil, carvedilol, cefminox, cefotiam, celgosivir, cevimeline, chlorcyclizine, chloroprocaine, chloropyramine, chlorotoxin I-131, cinnarizine, ciprofloxacin, cisapride, clarithromycin, clofedanol, clomocycline, clonidine, cloperastine, CNS-5161, cocaine, cyclacillin, cyclizine, cyclopentolate, cycloserine, cyproheptadine, darapladib, daunorubicin, DDP-225, demeclocycline, deramciclane, desvenlafaxine, dicyclomine, dihydroergotamine, diltiazem, dimenhydrinate, dimetotiazine, diphenhydramine, diphenoxylate, diphenylpyraline, dofetilide, donepezil, dotarizine, doxorubicin, doxylamine, droxidopa, d-serine, dyclonine, edetic acid, edivoxetine, elacridar, eletriptan, eliglustat, emedastine, enoxacin, eperisone, epinastine, epinephrine, epirubicin, erythromycin, ethoheptazine, famotidine, fasudil, fentanyl, flupentixol, fluphenazine, flurazepam, forodesine, friulimicin B, gaboxadol, gadoversetamide, galantamine, garenoxacin, gatifloxacin, glesatinib, glucosamine, glypromate, granisetron, grepafloxacin, haloperidol, hydrocodone, hydromorphone, idarubicin, imatinib, imolamine, indium In-111 pentetate, iroxanadine, isoaminile, isoprenaline, isothipendyl, isoxsuprine, istaroxime, itopride, ketobemidone, lasofoxifene, l-asparagine, levobupivacaine, levonordefrin, lincomycin, lobeline, lofentanil, lomefloxacin, l-threonine, lucanthone, lumateperone, lurasidone, LY-517717,Attorney Docket No.: 53160-716.601 managlinat dialanetil, masitinib, meclizine, melperone, mepyramine, mequitazine, mesoridazine, methdilazine, midodrine, migalastat, miglustat, mimosine, minocycline, moxisylyte, naloxegol, nebivolol, nelfinavir, nicardipine, nicergoline, nicotine, norepinephrine, norfloxacin, normethadone, ocaperidone, ohmefentanyl, orphenadrine, osimertinib, oxybuprocaine, oxybutynin, oxycodone, oxyphencyclimine, pafuramidine, palbociclib, paliperidone, paliroden, pargyline, PBT-1033, pelitinib, pentetate calcium trisodium, pentetate zinc trisodium, pentostatin, perphenazine, pethidine, p-fluorofentanyl, phenindamine, phenmetrazine, phenyltoloxamine, pimavanserin, pimozide, pipamperone, pipazethate, pipendoxifene, pipotiazine, pirlindole, ponatinib, PPI-1019, prilocaine, procaine, prochlorperazine, proflavine, proparacaine, propericiazine, propiomazine, propoxycaine, protokylol, prucalopride, PRX- 07034, quinagolide, quinupristin, rabeximod, ranitidine, rasagiline, remacemide, remoxipride, renzapride, rifabutin, rifalazil, rilapladib, risperidone, rivastigmine, robalzotan, rolapitant, rolitetracycline, roxatidine acetate, saquinavir, sarafloxacin, sarizotan, selegiline, serine, sertindole, sincalide, sitagliptin, solifenacin, sparfloxacin, spinosad, sufentanil, sulpiride, tacrine, talabostat, tamoxifen, tariquidar, technetium tc-99m tetrofosmin, tegaserod, terbinafine, terconazole, tetracaine, tetracycline, tetrofosmin, thienylfentanyl, thioproperazine, thioridazine, thiothixene, thonzylamine, tianeptine, tigecycline, tocainide, tolperisone, toremifene, trifluoperazine, trimebutine, trimethobenzamide, tripelennamine, triprolidine, tromethamine, tubocurarine, udenafil, vanoxerine, veliparib, venlafaxine, vicriviroc, vilazodone, viloxazine, vinblastine, vincristine, vindesine, vinorelbine, voacamine, vortioxetine, xaliproden, xanthinol, zanapezil, zotepine, zuclopenthixol, α-methylfentanyl, α-methylthiofentanyl, β- hydroxythiofentanyl, or a combination thereof. In some embodiments, the pharmaceutical compound has a pKa of about 9 to about 10. In some embodiments, the pharmaceutical compound comprises a 1-benzopyran, 1-benzothiopyran, 1-hydroxy-4-unsubstituted benzenoid, 4-quinolinemethanol, 5’-deoxy-5’-thionucleoside, amine, amino acid, peptide, aminophenyl ether, aminoquinoline, anilide, anisole, anthraquinone, benzenediol, benzenesulfonamide,benzo-1,4-dioxane, benzodiazine, benzoic acid, benzonitrile, benzoquinoline, benzoxazinon e,benzoyl, benzyl alcohol, benzylether, benzylpiperidine, beta lactam, biphenyl, bisphosphonate, carbazole, carbohydrate and carbohydrate conjugate, cytisine, depsipeptide, dibenzazepine, dibenzothiepin, dibenzoxepine, dicarboxylic acid, diphenylacetonitrile, diphenylmethane, diterpenoid, ether, fentanyl, glycerophosphoserine, halobenzene, hybrid peptide, hydropyridine, hydroquinoline, hydroxypyridine, indazole, indolecarboxylic acid, indole, indoline, indoloquinoline, indolyl carboxylic acid, isoquinoline quinone, lysergic acid, methoxybenzene, naphthyridine, nitrobenzene, nitroquinoline, organosulfonic acid, pentacarboxylic acid,Attorney Docket No.: 53160-716.601 phenethylamine, pheniramine, phenothiazine, phenoxazine, phenoxy compound, phenoxyacetic acid, phenylacetamide, phenylbutylamine, phenylmethylamine, phenylpiperidine, phenylpropane, phenyltropane, piperazine, piperidinecarboxylic acid, pregnane steroid, purines and purine, pyridinium, quinoline carboxylic acid, quinolone, steroid ester, styrene, substituted pyrrole, sulfanilide, tametraline, thiophene carboxylic acid, toluene, trifluoromethylbenzene, tryptamine, tyrosol, or a derivative thereof, or a combination thereof. In some embodiments, the pharmaceutical compound comprises (3S)-3-methyl-D-aspartic acid, isoxsuprine, 13- deoxydoxorubicin, 3-allylfentanyl, 3-methylfentanyl, 4-phenylfentanyl, 7-hydroxystaurosporine, acebutolol, ademetionine, aldoxorubicin, alendronic acid, alethine, alimemazine, aliskiren, almotriptan, alogliptin, alprenolol, ambroxol, amibegron, amikacin, amineptine, aminocandin, amitriptyline, amlodipine, amphotericin b, antazoline, apramycin, aprindine, arbaclofen, arbekacin, arbutamine, arformoterol, arimoclomol, arotinolol, arylacenamide, atenolol, atomoxetine, atosiban, atropine, azithromycin, bacitracin, baclofen, bambuterol, bazedoxifene, becatecarin, benfluorex, benzatropine, benzphetamine, benzydamine, benzylpenicilloyl polylysine, bepotastine, bepridil, besifloxacin, betahistine, betaxolol, betazole, bevantolol, bilastine, bimoclomol, biperiden, bisoprolol, bopindolol, brasofensine, bromhexine, bromopride, brompheniramine, bufuralol, bupranolol, butenafine, cabergoline, canfosfamide, carbocisteine, carteolol, caspofungin, cediranib, ceforanide, ceftolozane, celiprolol, chlorphenamine, chlorpromazine, chlorprothixene, cilastatin, cinchocaine, cinitapride, citalopram, clemastine, clenbuterol, clocapramine, clofazimine, clomifene, clomipramine, cobimetinib, codeine, colestipol, CP-122721, cyamemazine, cyclobenzaprine, cycrimine, cystine, cytisine, dalbavancin, dapoxetine, daptomycin, darinaparsin, declopramide, demexiptiline, desloratadine, dexbrompheniramine, dexchlorpheniramine maleate, dexmethylphenidate, dextromethorphan,dextropropoxyphene, dextrothyroxine, dezocine, difenoxin, dihydrocodeine, dimetacrine,dimetindene, diphenidol, dipivefrin, diprenorphine, dirithromycin, D-methionine, dobutamine, dopamine, doripenem, dosulepin, doxepin, dronedarone, duloxetine, encainide, enclomiphene, ephedrine, epicept NP-1, eribulin, ertapenem, escitalopram, esmolol, ethambutol, ethopropazine, ethylmorphine, etidocaine, etryptamine, fenoterol, fenspiride, ferrous bisglycinate, fexofenadine, filanesib, fingolimod, flecainide, fluoxetine, fluspirilene, fluvoxamine, formoterol, framycetin, gabapentin, gadobenic acid, gadofosveset trisodium, gadopentetate dimeglumine, gadoteridol, gadoxetic acid, gemifloxacin, glutamic acid, glutathione, glutathione disulfide, glycine, golotimod, gosogliptin, granisetron, halofuginone, heroin, hexetidine, hexylcaine, histamine, histidine, homatropine, huperzine A, huperzine B, hydroxyamphetamine, hydroxychloroquine, hyoscyamine, ibandronate, ifenprodil, imipramine, indacaterol, ioflupane I-123, irinotecan,Attorney Docket No.: 53160-716.601 isoetarine, ispinesib, ivabradine, K201, kanamycin, labetalol, L-alanine, L-aspartic acid, L- citrulline, L-cysteine, lercanidipine, leukotriene C4, levallorphan, levamlodipine, levobetaxolol, levobunolol, levodopa, levomethadyl acetate, levomilnacipran, levorphanol, levothyroxine, L- glutamine, linagliptin, liothyronine, liotrix, L-isoleucine, LJP 1082, L-leucine, lomitapide, loperamide, L-phenylalanine, L-threonine, L-tryptophan, L-tyrosine, lumefantrine, L-valine, lymecycline, mafenide, magnesium glycinate, mefloquine, melphalan, meropenem, metaraminol, methadone, methadyl acetate, methionine, methotrimeprazine, methoxamine, methyldopa, methylphenidate, metipranolol, metixene, metoclopramide, metoprolol, metyrosine, mexiletine, mibefradil, milnacipran, mirabegron, mitemcinal, mitoxantrone, mn-305, morphine, moxifloxacin, nadolol, naftifine, nalmefene, naratriptan, naronapride, natamycin, nemonoxacin, netilmicin, nitroarginine, NPS-2143, NS-2359, nystatin, oglufanide, olodaterol, olopatadine, omacetaxine mepesuccinate, OPC-28326, orciprenaline, osanetant, oseltamivir, oxamniquine, oxilofrine, oxitriptan, oxprenolol, pamidronate, paromomycin, paroxetine, penbutolol, penicillamine, pentoxyverine, pergolide, phenaridine, phenindamine, pheniramine, phentolamine, phenylephrine, phenylpropanolamine, pholcodine, phosphatidyl serine, piboserod, pindolol, piperazine, pirarubicin, pirbuterol, pixantrone, polaprezinc, pracinostat, practolol, procainamide, procaterol, procyclidine, promazine, promethazine, propafenone, propoxyphene napsylate, propranolol, PRX-03140, pseudoephedrine, PX-478, quarfloxin, quinidine, quinidine barbiturate, quinine, repinotan, retapamulin, ribostamycin, ritodrine, rizatriptan, ronacaleret, roxithromycin, salbutamol, salmeterol, saredutant, selenomethionine, seproxetine, serotonin, sertraline, sibutramine, silodosin, siramesine, solabegron, sotalol, spectinomycin, spiramycin, sumanirole, sumatriptan, sunitinib, tamsulosin, tandutinib, tapentadol, TAS-108, taurine, tedisamil, telavancin, terbutaline, terfenadine, tesmilifene, tesofensine, tetrodotoxin, TG-100801, tiagabine, ticalopride, tilmicosin, timolol, tobramycin, topotecan, tramadol, tranylcypromine, triethylenetetramine, triflupromazine, trihexyphenidyl, trimetazidine, trimipramine, trovafloxacin, tyramine, ubenimex, vancomycin, vandetanib, varenicline, vecuronium, verapamil, vernakalant, vigabatrin, vilanterol, vildagliptin, zolmitriptan, α-methylacetylfentanyl, α-methylfentanyl, β-methylfentanyl, or a combination thereof. In some embodiments, the pharmaceutical compound has a pKa of about 10 to about 13. In some embodiments, the pharmaceutical compound comprises 2,6-dimethyl-3-benzazocine, alkaline earth metal oxide, alkylthiol, amine, amino acid, peptide, aminopyridine, aminoquinoline, benzenediol, benzoic acid, benzoquinoline, beta lactam, bile acid, alcohol, biphenyl, bisphosphonate, carbazole, carbohydrates and carbohydrate conjugate, carboxylic acid derivative, cyclohexylamine, depsipeptide, dibenzazepine, diphenylmethane, ether, fatty acidsAttorney Docket No.: 53160-716.601and conjugate, guanidine, halobenzene, hybrid peptide, indolecarboxylic acid, indole , indoline,monoterpenoid, n-arylamide, organosulfonic acid, peptoid-peptide hybrid, phenethylamine, pheniramine, phenylbutylamine, phenylmethylamine, phenylpiperidine, phenylpropane, phenylpropylamine, phenylpyridine, piperidinecarboxylic acid, purines and purine derivative, pyrazolylpyridine, pyrimidines and pyrimidine derivative, tetracarboxylic acid, tryptamine, urea, xylene, or a derivative thereof, or a combination thereof. In some embodiments, the pharmaceutical compound comprises 2-iminobiotin, abarelix, ABT-510, afamelanotide, agmatine, alverine, alvimopan, amantadine, AMD-070, amifostine, aminocaproic acid, amodiaquine, amphetamine, anatibant, apomorphine, argatroban, arverapamil, atiprimod, aviptadil, bedoradrine, benzoctamine, bethanidine, bicifadine, bivalirudin, brostallicin, buformin, buprenorphine, butorphanol, butriptyline, capreomycin, carbamide peroxide, ceftobiprole, ceritinib, cetrorelix, chlorhexidine, chloroquine, chlorphentermine, cinacalcet, corticorelin ovine triflutate, cr665, creatine, crizotinib, cysteamine, CZEN 002, dalfampridine, darifenacin, debrisoquin, deferoxamine, degarelix, delcasertib, denibulin, desipramine, deslorelin, desmopressin, dexfenfluramine, dextroamphetamine, diethylnorspermine, dihydrostreptomycin, disopyramide, eflornithine, enviomycin, etorphine, felypressin, fencamfamine, fenethylline, fenfluramine, fenoldopam, fesoterodine, fradafiban, frovatriptan, fursultiamine, gadoteric acid, gadoteridol, gamma-aminobutyric acid, ganirelix, gentamicin, gonadorelin, goserelin, guanadrel, guanethidine, guanidine, halofantrine, hexoprenaline, histrelin, hydroxyproline, hydroxystilbamidine isethionate, ibutilide, icatibant, imipenem, indalpine, indecainide, iobenguane, iobenguane sulfate I-123, isometheptene, labradimil, L- aminocarnityl-succinyl-leucyl-argininal-diethylacetal, lanreotide, L-arginine, L-eflornithine, levmetamfetamine, levocabastine, lisdexamfetamine, lisinopril, lixisenatide, L-lysine, lorcaserin, L-proline, magnesium oxide, maprotiline, maraviroc, mecamylamine, memantine, mephentermine, metformin, methamphetamine, midomafetamine, nafarelin, nalbuphine, naltrexone, naphazoline, neramexane, neridronic acid, nintedanib, nor-noha, nortriptyline, nylidrin, obinepitide, octreotide, olcegepant, oritavancin, ornithine, otamixaban, oxymetazoline, oxymorphone, panobinostat, pasireotide, pemetrexed, pentamidine, pentazocine, peramivir, perhexiline, phencyclidine, phenformin, phentermine, pimagedine, piracetam, plerixafor, polymyxin B sulfate, pozanicline, pramipexole, pregabalin, prezatide, primaquine, progabide, proguanil, propylhexedrine, protriptyline, pyrantel, quinacrine, ramoplanin, rifaximin, rimantadine, rivanicline, romidepsin, ropinirole, rotigotine, saralasin, satraplatin, serotonin, SGS-742, sitamaquine, SNS-032, somatostatin, spermine, SQ-109, squalamine, streptomycin, T131, tafenoquine, talotrexin, tanespimycin, tecastemizole, tenocyclidine, terlipressin,Attorney Docket No.: 53160-716.601 tesamorelin, tetracosactide, tetryzoline, tezampanel, tipiracil, tirofiban, tolazoline, tolterodine, tramiprosate, tranexamic acid, triptorelin, ularitide, urea C-13, vapitadine, vintafolide, viomycin, WX-UK1, xylometazoline, zanamivir, or a combination thereof. In some embodiments, the pharmaceutical composition is a solid. In some embodiments, the pharmaceutical compound has a pKa of at least 2. In some embodiments, the pharmaceutical compound has a pKa of about 2 to about 7.5. In some embodiments, the pharmaceutical compound has a pKa of about 1 to about 5. In some embodiments, the pharmaceutical compound has a pKa of about 7.5 to about 11. In some embodiments, the pharmaceutical composition is formulated as a liquid. In some embodiments, the pharmaceutical compound has a pKa of at least 5. In some embodiments, the pharmaceutical compound has a pKa of about 5 to about 7. In some embodiments, the pharmaceutical composition when formulated as a solution has a lower osmolality than a solution comprising the composition comprising a salt of the pharmaceutical compound and a salt of the complexing agent. In some embodiments, the pharmaceutical composition improves a solubility of the pharmaceutical compound by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or about 100% as compared to a composition (i) without the complexing agent or (ii) wherein the pharmaceutical compound does not complex with one of more of the acidic functional groups of the complexing agent. In some embodiments, the pharmaceutical composition improves a solubility of the pharmaceutical compound by about 2-fold, about 3-fold, about 4-fold, about 5-fold, about 6-fold, about 7-fold, about 8-fold, about 9-fold, about 10-fold, about 20-fold, about 30-fold, about 40-fold, or about 50-fold as compared to a composition (i) without the complexing agent or (ii) wherein the pharmaceutical compound does not complex with one of more of the acidic functional groups of the complexing agent. In some embodiments, the complexing agent comprises a substituted cyclodextrin. In some embodiments, the complexing agent comprises a cyclodextrin substituted with at least one acidic functional group. In some embodiments, the cyclodextrin is substituted with 3 to 8 acidic functional groups. In some embodiments, the cyclodextrin is sulfobutylether- β-cyclodextrin (SBEBCD). In some embodiments, the pharmaceutical composition when formulated as a solution has a lower osmolality than a solution comprising a composition comprising a salt of the pharmaceutical compound and a salt of the complexing agent. In some embodiments, the pharmaceutical is formulated for subcutaneous, intramuscular, sublingual, oral, rectal, transvaginal, or intranasal administration. In some embodiments, the pharmaceutical composition when formulated as a solution has an osmolality of no more than about 850 mOsm / kg. In some embodiments, the pharmaceutical composition has a pH of about 4 to about 7. In some embodiments, the complexing agent is present in an amount of about 10 mg / mL toAttorney Docket No.: 53160-716.601 about 600 mg / mL. In some embodiments, the complexing agent acts as the counterion to between 1 to 10 molecules of the pharmaceutical compound. In some embodiments, the complexing agent further comprises a non-polar pore. In some embodiments, the pharmaceutical composition further comprises an additional molar equivalent of the pharmaceutical compound, wherein the additional molar equivalent of the pharmaceutical compound is unionized and complexed to the non-polar pore. In some embodiments, the ratio of complexing agent to the pharmaceutical compound is about 1:1.1. In some embodiments, the ratio of complexing agent to the pharmaceutical compound is about 1:2. In some embodiments, the ratio of complexing agent to the pharmaceutical compound is about 1:3. In some embodiments, the ratio of complexing agent to the pharmaceutical compound is about 1:4. In some embodiments, the ratio of complexing agent to the pharmaceutical compound is about 1:5. In some embodiments, the ratio of complexing agent to the pharmaceutical compound is about 1:6.5. In some embodiments, the pharmaceutical compound has a solubility of less than about 50 mg / ml as salt in an aqueous medium. In some embodiments, the pharmaceutical compound has a solubility of less than about 10 mg / ml as salt in an aqueous medium. In some embodiments, the pharmaceutical compound has a solubility of less than about 5 mg / ml as salt in an aqueous medium. In some embodiments, the pharmaceutical compound has a solubility of less than about 0.5 mg / ml as salt in an aqueous medium. In some embodiments, the pharmaceutical compound has a solubility of less than about 0.1 mg / ml as salt in an aqueous medium. In some embodiments, the pharmaceutical compound is ionized. In some embodiments, the pharmaceutical compound comprises rotigotine, eletriptan, DXM, midazolam, remdesivir, copanlisib, melevodopa, tigecycline, naloxone, amikacin, 1-amantadine, 2-amantadine, rimantadine, amifampridine, rapamycin, clonidine, morphine, hydrocodone, sumatriptan,ropivacaine, bupivacaine, diphenhydramine, granistetron, deschloroketamine, 2 -fluoro-deschloroketamine, or caspofungin. In some embodiments, the pharmaceutical compound comprises a GABA-ergic. In some embodiments, the GABA-ergic comprises Baclofen, Gaboxidol, or Muscimol, or a combination thereof. In some embodiments, the pharmaceutical compound comprises an alpha-2 agonist. In some embodiments, the alpha-2 agonist comprises Clonidine, Guanfacine, or Tizanidine, or a combination thereof. In some embodiments, the pharmaceutical compound is an ophthalmic. In some embodiments, the ophthalmic comprises aceclidine, atropine, azelastine, brimonidine, cyclopentolate, ketotifen, levobunolol, olopatadine, pilocarpine, proparacaine, tetracaine, timolol, or tropicamide. In some embodiments, thepharmaceutical compound is a bisphosphonate. In some embodiments, the bisphosph onate isalendronate, ibandronate, pamidronate, risedronate, or zoledronic acid, or a combination or twoAttorney Docket No.: 53160-716.601 or more thereof. In some embodiments, the pharmaceutical compound is an antibiotic. In some embodiments, the antibiotic comprises amikacin, amoxicillin, ampicillin, azithromycin, aztreonam, cefaclor, cefadroxil, cefalexin, cefazolin, cefdinir, cefditoren, cefepime, cefiderocol, cefixime, cefmetazole, cefoperazone, cefotaxime, cefotetan, cefovecin, cefoxitin, cefpodoxime, cefprozil, ceftaroline, ceftazidime, ceftibuten, ceftizoxime, ceftolozane, ceftriaxone, cefuroxime, cephalexin, cephalothin, cephapirin, cephradine, ciprofloxacin, clarithromycin, clindamycin, colistin, dalbavancin, dalfopristin, daptomycin, doripenem, doxycycline, ertapenem, eravacycline, erythromycin, fosfomycin, gentamicin, imipenem, kanamycin, lefamulin, levofloxacin, linezolid, lincomycin, meropenem, metronidazole, minocycline, moxifloxacin, nalidixic acid, neomycin, nitrofurantoin, oritavancin, penicillin, piperacillin, polymyxin B, quinupristin, retapamulin, rifampicin, streptomycin, sulfacetamide, sulfadiazine, sulfamethizole, sulfamethoxazole, sulfasalazine, sulfisoxazole, teicoplanin, telavancin, tetracycline, tigecycline, tobramycin, trimethoprim, or vancomycin, or a combination thereof. In some embodiments, the pharmaceutical compound is an anticoagulant or a thrombolytic. In some embodiments, the anticoagulant or thrombolytic comprises alteplase, argatroban, bivalirudin, fondaparinux, lepirudin, streptokinase, or urokinase, or a combination or two or more thereof. In some embodiments, the pharmaceutical compound is an antifungal. In some embodiments, the antifungal comprises an azole antifungal. In some embodiments, the antifungal comprisesalbendazole, clotrimazole, econazole, f luconazole, isavuconazole, itraconazole, ketoconazole,miconazole, posaconazole, tebuconazole, thiabendazole, or voriconazole, or a combination or two or more thereof. In some embodiments, the antifungal is amphotericin B, anidulafungin, caspofungin, flucytosine, micafungin, natamycin, or voriconazole, or a combination or two or more thereof. In some embodiments, the pharmaceutical compound is an antineoplastic. In some embodiments, the antineoplastic is afatinib, alectinib, alisertib, axitinib, bosutinib, cabozantinib, canertinib, carfilzomib, cediranib, ceritinib, cimicoxib, cobimetinib, dabrafenib, darapladib, dasatinib, delcasertib, dovitinib, erlotinib, etoricoxib, filanesib, glesatinib, ibrutinib, idelalisib, imatinib, ispinesib, ixazomib, lapatinib, lenvatinib, linsitinib, lonafarnib, masitinib, motesanib, nilotinib, nintedanib, odanacatib, olaparib, onalespib, osimertinib, palbociclib, pazopanib, pelitinib, ponatinib, regorafenib, rilapladib, ruxolitinib, seliciclib, sonidegib, sorafenib, sunitinib, tandutinib, tipifarnib, tofacitinib, vandetanib, varlitinib, varlitinib, vatalanib, veliparib, vemurafenib, vismodegib, or a combination or two or more thereof. In some embodiments, thepharmaceutical compound is an antiviral. In some embodiments, the antiv iral comprisesabacavir, acyclovir, adefovir, amantadine, amprenavir, atazanavir, bictegravir, cidofovir, darunavir, dasabuvir, delavirdine, didanosine, dolutegravir, efavirenz, elvitegravir, emtricitabine,Attorney Docket No.: 53160-716.601 enfuvirtide, entecavir, famciclovir, foscarnet, ganciclovir, grazoprevir, imiquimod, indinavir, lamivudine, laninamivir, ledipasvir, lopinavir, maraviroc, nelfinavir, nevirapine, ombitasvir, oseltamivir, paritaprevir, penciclovir, peramivir, plerixafor, podofilox, raltegravir, ribavirin, rilpivirine, ritonavir, saquinavir, sofosbuvir, stavudine, tenofovir, tipranavir, trifluridine, valaciclovir, valganciclovir, zanamivir, or zidovudine, or a combination thereof. In some embodiments, the pharmaceutical compound comprises a cardiovascular medication. In some embodiments, the cardiovascular medication comprises Bretylium, Dobutamine, Dopexamine, Epoprostenol, Esmolol, Iloprost, Nesiritide, Nitroglycerin, Norepinephrine, or Phenylephrine, or a combination or two or more thereof. In some embodiments, the pharmaceutical compound comprises a central nervous system depressant. In some embodiments, the central nervous system depressant comprises alprazolam, chlordiazepoxide, clonazepam, diazepam, dexmedetomidine, dextromethorphan, flurazepam, gabapentin, ketamine, lorazepam, midazolam, oxazepam, propofol, temazepam, or triazolam, or a combination or two or more thereof. In some embodiments, the pharmaceutical compound comprises a central nervous system stimulant. In some embodiments, the central nervous system stimulant comprises amphetamine, cocaine, dexmethylphenidate, dextroamphetamine, ephedrine, lisdexamfetamine, methamphetamine, methylphenidate, modafinil, phenylephrine, pseudoephedrine, or sibutramine, or a combination or two or more thereof. In some embodiments, the pharmaceutical compound comprises a local anesthetic. In some embodiments, the local anesthetic comprises articaine, benzocaine, bupivacaine, chloroprocaine, cocaine, dibucaine, etidocaine, levobupivacaine, lidocaine, mepivacaine, prilocaine, procaine, proparacaine, ropivacaine, or tetracaine, or a combination thereof. In some embodiments, the pharmaceutical compound comprises an anti-nausea medicine. In some embodiments, the anti-nausea medicine comprises dolasetron, granisetron, ondansetron, or palonosetron, or a combination thereof. In some embodiments, the pharmaceutical compound is an anti-migraine. In some embodiments, the anti-migraine comprises almotriptan, avitriptan, donitriptan, eletriptan, frovatriptan, lasmiditan, naratriptan, rizatriptan, sumatriptan, or zolmitriptan, or a combination thereof. In some embodiments, the pharmaceutical compound comprises an anti-Parkinson’s medicine. In some embodiments, the anti-Parkinson’s medicine comprises amantadine, apomorphine, benztropine, benserazide, bromocriptine, cabergoline, carbidopa, entacapone, foscarbidopa, foslevodopa, levodopa, melvodopa, pramipexole, rasagiline, ropinirole, rotigotine, safinamide, selegiline, tolcapone, or trihexyphenidyl, or a combination thereof. In some embodiments, the pharmaceutical compound comprises an antihistamine. In some embodiments, the antihistamine comprises acrivastine, brompheniramine, cetirizine, chlorpheniramine, clemastine,Attorney Docket No.: 53160-716.601 cyproheptadine, desloratadine, dexchlorpheniramine, diphenhydramine, doxylamine, fexofenadine, hydroxyzine, levocetirizine, loratadine, meclizine, promethazine, or tripelennamine, or a combination thereof. In some embodiments, the pharmaceutical compound comprises an H2 histamine receptor blocker. In some embodiments, the H2 histamine receptor blocker is cimetidine, famotidine, nizatidine, or ranitidine, or a combination thereof. In some embodiments, the pharmaceutical compound comprises an opioid. In some embodiments, the opioid comprises buprenorphine, butorphanol, codeine, fentanyl, heroin, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, naloxone, naltrexone, nalmefene, oxycodone, oxymorphone, pentazocine, sufentanil, tapentadol, or tramadol, or a combination or two or more thereof. In some embodiments, the pharmaceutical compound is a tyrosine kinase inhibitor. In some embodiments, the tyrosine kinase inhibitor comprises bosutinib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, ponatinib, sorafenib, or sunitinib or two or more thereof. In some embodiments, the pharmaceutical compound comprises amifampridine, amifostine, aminocaproic acid, argatroban, asenapine, atropine, bivalirudin, cisatracurium, deferoxamine, desmopressin, gabapentin, lurasidone, milrinone, nicotine, octreotide, pregabalin, rocuronium, terbutaline, tirofiban, tranexamic acid, vecuronium, nepafenac, or any combination thereof.

[0004] In some aspects provided herein are pharmaceutically acceptable salts of a compound pharmaceutical comprising: a pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the pharmaceutical compound comprises a protonated nitrogen atom and a pKa of about 1 to about 7; and a conjugate base of a complexing agent comprising a plurality of acidic functional groups, wherein at least one acidic functional group of the plurality of acidic functional groups acts as a counterion of the pharmaceutical compound, wherein the molar ratio of the conjugate base of the complexing agent to the pharmaceutical compound is from about 1:1 to about 1:10. In some aspects provided herein are pharmaceutically acceptable salts of a compound pharmaceutical comprising: a pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the pharmaceutical compound comprises a protonated nitrogen atom and a pKa of at least 1; and a conjugate base of a complexing agent comprising a plurality of acidic functional groups, wherein at least one acidic functional group of the plurality of acidic functional groups acts as a counterion of the pharmaceutical compound, wherein the molar ratio of the conjugate base of the complexing agent to the pharmaceutical compound is from about 1:1 to about 1:10. In some aspects provided herein are pharmaceutically acceptableAttorney Docket No.: 53160-716.601 salts of a compound pharmaceutical comprising: a pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the pharmaceutical compound comprises a protonated nitrogen atom and a pKa of about 1 to about 13; and a conjugate base of a complexing agent comprising a plurality of acidic functional groups, wherein at least one acidic functional group of the plurality of acidic functional groups acts as a counterion of the pharmaceutical compound, wherein the molar ratio of the conjugate base of the complexing agent to the pharmaceutical compound is from about 1:1 to about 1:10. In some aspects provided herein are pharmaceutically acceptable salts of a compound pharmaceutical comprising: a pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the pharmaceutical compound comprises a protonated nitrogen atom and a pKa of about 4 to about 13; and a conjugate base of a complexing agent comprising a plurality of acidic functional groups, wherein at least one acidic functional group of the plurality of acidic functional groups acts as a counterion of the pharmaceutical compound, wherein the molar ratio of the conjugate base of the complexing agent to the pharmaceutical compound is from about 1:1 to about 1:10. In some embodiments, the complexing agent comprises a substituted cyclodextrin. In some embodiments, the complexing agent comprises a cyclodextrin substituted with at least one acidic functional group. In some embodiments, the cyclodextrin is substituted with 3 to 8 acidic functional groups. In some embodiments, the cyclodextrin is sulfobutylether-β-cyclodextrin (SBEBCD). In some embodiments, the pharmaceutical compound has a pKa of at least 1. In some embodiments, the pharmaceutical compound has a pKa of about 1 to about 7.5. In some embodiments, the pharmaceutical compound has a pKa of about 1 to about 5. In someembodiments, the pharmaceutical compound has a pKa of about 7.5 to about 13. In so meembodiments, the pharmaceutical compound comprises 5'-deoxyribonucleosides, 6,7- benzomorphans, ajmaline-sarpagine alkaloids, alkaline earth metal organides, amaryllidaceaealkaloids, anthracenes, anthracyclines, aporphines, azaspirodecane, azepanes, azo benzenes,azoles, azolidines, azolines, benzazepines, benzene and substituted, benzimidazole ribonucleosides and ribonucleotides, benzimidazoles, benzocycloheptapyridines,benzodiazepines, benzodioxanes, benzodioxoles, benzofurans, benzopyrans, benzopyrazo les,benzothiadiazoles, benzothiazepines, benzothiazines, benzothiazoles, benzothiepins, benzothiophenes, benzothiopyrans, benzotriazoles, benzoxadiazoles, benzoxazepines, benzoxazines, benzoxepines, biotin, camptothecins, carboxylic acids, cephalotaxus alkaloids, cinchona alkaloids, cinnamic acids, coumarans, cycloheptathiophenes, depsides and depsidones,Attorney Docket No.: 53160-716.601 diarylheptanoids, diazanaphthalenes, diazinanes, diazines, dibenzocycloheptenes, dioxanes, epoxides, ergoline, fatty acyls, flavin nucleotides, flavonoids, fluorenes, furans, furopyrans, glycerophospholipids, homogeneous other non-metal compounds, hydroxy acids, ibogan-type alkaloids, imidazodiazepines, imidazole ribonucleosides and ribonucleotides, imidazopyridines, imidazopyrimidines, imidazothiazoles, indanes, indenes and isoindenes, indoles, indolizidines, isocoumarans, isoindoles, isoquinolines, lactams, linear 1,3-diarylpropanoids, lupin alkaloids, macrolactams, macrolide lactams, macrolides morphinans, naphthacenes, naphthalenes, naphthofurans, naphthopyrans, nucleoside and nucleotide analogues, organic carbonic acids, organic phosphines, organic phosphonic acids, organic sulfonic acids, organonitrogen compounds, organooxygen compounds, organothiophosphorus compounds, oxazinanes, peptidomimetics, phenanthrenes, phenanthrolines, phenol esters, phenol ethers, phenols, phenylpropanoic acids, phthalide isoquinolines, piperazinoazepines, piperidines, polypeptides, prenol lipids, pteridines, purine nucleosides, purine nucleotides, pyrazolopyridines, pyrazolopyrimidines, pyridines, pyridopyrimidines, pyrimidine nucleosides, pyrroles, pyrrolidines, pyrrolopyrazines, pyrrolopyridines, pyrrolopyrimidines, quinolines, steroids andsteroid, stilbenes, tetracyclines, tetrahydroisoquinolines, tetralins, thiadiazines, thienodiazepines,thienopyridines, thienothiazines, thiochromenes, thioethers, thiols, thiophenes, transition metal salts, triazinanes, triazines, triazole ribonucleosides and ribonucleotides, triazolopyrimidines, triphenyl compounds, tropane alkaloids, vinca alkaloids, yohimbine alkaloids, or a derivative thereof, or a combination thereof. In some embodiments, the pharmaceutical compound has a pKa of about 1 to about 2. In some embodiments, the pharmaceutical compound comprises a 1,4-benzodiazepine, amine, amino acid, peptide, androstane steroid, benzenesulfonamide, benzoic acids, benzophenone, benzothiadiazine, biphenyls, carboxylic acid derivative, depsipeptide, diphenylmethane, ether, halobenzene, isoindoline, nitrogen mustard compound, nitroquinolines, purine 2’-deoxyribonucleoside, purines, pyrazole, pyrimidines or derivative thereof, retinoid, substituted pyrrole, or a combination thereof. In some embodiments, the pharmaceutical compound comprises apadenoson, asunaprevir, azilsartan medoxomil, benzthiazide, bromfenac, candesartan cilexetil, carbazochrome, chlorambucil, chlorothiazide, cladribine, clofarabine, clonazepam, CVT-6883, CX516, dacarbazine, diazoxide, emodepside, fimasartan, flubendazole, flucytosine, fludiazepam, flunitrazepam, ganciclovir, gliclazide, glisoxepide, grazoprevir, guanosine, ibudilast, ibuproxam, iocetamic acid, iopamidol, iopanoic acid, isatoribine, ixazomib, MB-07803, nateglinide, nepafenac, OPC-51803, pleconaril, pomalidomide, pralnacasan, pyrvinium, regadenoson, rimonabant, selexipag, simeprevir, sulfadimethoxine, sulfamerazine, sulfameter, sulfamethizole, sulfamethoxazole,Attorney Docket No.: 53160-716.601 sulfametopyrazine, sulfamoxole, taranabant, tazarotene, tiopronin, tolazamide, trapidil, uracil mustard, or a combination thereof. In some embodiments, the pharmaceutical compound has a pKa of about 2 to about 3. In some embodiments, the pharmaceutical compound comprises azobenzene, azole, benzazepine, benzene, benzodiazepine, benzothiazine, benzothiazole, carboxylic acid, depside, diazanaphthalene, diazine, imidazopyrimidine, indole, isoindole, lactam, macrolides naphthalene, nucleoside and nucleotide analogue, organooxygen compound, piperidine, prenol lipid, pteridine, purine nucleoside, purine nucleotide, pyrazolopyrimidine, pyridine, pyrimidine nucleoside, pyrrolopyridine, quinoline, steroid, thienodiazepine, triazine, triazolopyrimidine, or a combination thereof. In some embodiments, the pharmaceutical compound comprises 1,4-benzodiazepine, amino acid, peptide, aminotriazine, androstane steroid, anilide, aniline, benzazepine, benzenesulfonamide, benzenesulfonyl compound, benzodiazine, benzoic acids, beta lactam, biphenyl, carbazole, diphenylether, diphenylmethane, epothilones estrane steroid, ether, halobenzene, isoindoline, milbemycin, monoterpenoid, nitroquinolines, oxosteroid, phenoxyacetic acid derivative, phenylbutylamine, phenylcarbamicacid ester, phenylmethylamine, phenylpropane, phenylquinoline, pterins, purine 2',3' -dideoxyribonucleoside, purine ribonucleotide, purines and purine derivative, pyra zole,pyrazolo[3,4-d]pyrimidine, pyridinecarboxylic acids, pyrimidines and pyrimidine derivative, sulfanilide, or a combination thereof. In some embodiments, the pharmaceutical compound comprises aciclovir, adipiplon, alisertib, allopurinol, ambrisentan, amelubant, aminobenzoic acid, aminopterin, aminosalicylic acid, amprenavir, anastrozole, arsanilic acid, asoprisnil, benzocaine, BMS-488043, brecanavir, bromazepam, bumetanide, butamben, cangrelor, cefixime, cefpiramide, chromium picolinate, cidofovir, ciluprevir, cinalukast, clazosentan, clotiazepam, cloxazolam, dabrafenib, dapsone, darunavir, delorazepam, diazepam, didanosine, dutasteride, edotecarin, efonidipine, elacytarabine, entecavir, epirizole, epothilone d, finasteride, fluconazole, flutemetamol (18F), folic acid, fomepizole, fosamprenavir, ganstigmine, GW- 501516, halazepam, indocyanine green, inosine, iodamide, iopromide, isavuconazole, ixabepilone, KOS-1584, KP-1461, lenalidomide, letrozole, leucovorin, levoleucovorin, macitentan, meradimate, mercaptopurine, methotrexate, methylene blue, methylthioninium, motexafin gadolinium, motexafin lutetium, moxidectin, naxifylline, nitrazepam, nitroxoline, olaparib, ombitasvir, OT-551, padimate O, paritaprevir, patupilone, penciclovir, phenyl aminosalicylate, PPL-100, pralatrexate, quazepam, ravuconazole, regorafenib, regrelor, ritonavir, roflumilast, roxadustat, silver sulfadiazine, sorafenib, stanozolol, sulfabenzamide, sulfacetamide, sulfacytine, sulfadiazine, sulfadoxine, sulfamerazine, sulfamethazine, sulfanilamide, sulfaphenazole, sulfapyridine, sulfasalazine, sulfathiazole, sulfisoxazole,Attorney Docket No.: 53160-716.601 talnetant, tasosartan, technetium tc-99m disofenin, technetium tc-99m mebrofenin, tezosentan, ticagrelor, tirapazamine, troxacitabine, trypan blue, voriconazole, or a combination thereof. In some embodiments, the pharmaceutical compound has a pKa of about 3 to about 4. In some embodiments, the pharmaceutical compound comprises a 1,4-benzodiazepine, amino acid, peptide, anilide, aniline and substituted aniline, anisole, aryl thioether, benzodiazine, benzofuranone, benzoic acids and derivative, benzophenone, beta lactam, biphenyls and derivative, bipyridines and oligopyridine, carbodiimide, diphenylether, diphenylmethane, epothilones estrane steroid, ether, haloquinoline, hexacarboxylic acids and derivative, imidazole, isoindole, milbemycin, morpholine, phenoxyacetic acid derivative, phenylmethylamine, phenylpyridine, piperazine, pterins and derivative, purine 2’,3’-dideoxyribonucleoside, purines and purine derivative, purines and purine derivative, pyrazine, pyrazole, pyridine carboxaldehyde, pyridinecarboxylic acids and derivative, pyridinesulfonamide, pyridyltriazole, steroid ester, sulfanilide, sulfinylbenzimidazole, or a combination thereof. In some embodiments, the pharmaceutical compound comprises adenosine, amiloride, aminobenzoic acid, aminophenazone, anagrelide, aprepitant, arsanilic acid, azathioprine, aztreonam, benzocaine, benzonatate, bisacodyl, bromazepam, brotizolam, bumetanide, butamben, calcium carbimide, cefepime, cefixime, cefmenoxime, cefotaxime, cefpodoxime, ceftizoxime, ceftriaxone, chloroxine, chromium picolinate, clioquinol, dabigatran etexilate, dabrafenib, dexlansoprazole, dexrazoxane, diazepam, didanosine, diiodohydroxyquinoline, entecavir, etofibrate, etravirine, ezogabine, flumazenil, flutemetamol (18F), indocyanine, inosine, inositol nicotinate, iopodic acid, irbesartan, isocarboxazid, isocarboxazid, isoniazid, itraconazole, ixabepilone, lansoprazole, leucovorin, levoleucovorin, levomefolic acid, lobeglitazone, losartan, lumacaftor, mazindol, mebendazole, mercaptopurine, mercaptopurine, methotrexate, metronidazole, metronidazole, montelukast, montelukast, moxidectin, nelarabine, niacin, nicorandil, nicotinamide, norelgestromin, norgestimate, oxfendazole, padimate o, pantoprazole, penciclovir, perampanel, picosulfuric acid, piroxicam, posaconazole, pralatrexate, prazepam, procaine merethoxylline, pyridoxal, pyridoxal phosphate, riociguat, ritonavir, stanozolol, talniflumate, tasosartan, tenofovir disoproxil, thiabendazole, thonzonium, ticagrelor, tinidazole, tioguanine, topiroxostat, torasemide, triamterene, triamterene, vemurafenib, vemurafenib, vismodegib, or a combination thereof. In some embodiments, the pharmaceutical compound has a pKa of about 4 to about 5. In some embodiments, the pharmaceutical compound comprises 1,4-benzodiazepine, 1-ribosyl-imidazolecarboxamide, 2-benzimidazolylcarbamic acid ester, 8- hydroxyquinoline, amine, amino acid, peptide, androstane steroid, anilide, aniline and substituted aniline, anthraquinone, aryl thioether, benzodiazine, benzoic acids and derivative,Attorney Docket No.: 53160-716.601 beta lactam, biphenyls and derivative, bipyridine, oligopyridine, bisphosphonate, carbonyl compound, diphenylmethane, ether, hexacarboxylic acids and derivative, imidazole, imidazoquinoline, indolequinone, naphthyridine, oxosteroid, phenethylamine, phenylbenzimidazole, phenylhydrazine, phenylpiperidine, phenylpyridine, phenylquinoline, pterins and derivative, purine ribonucleotide, purines and purine derivative, pyrazolo[1,5- a]pyrimidine, pyridine carboxaldehyde, pyridinecarboxylic acids and derivative, pyridinesulfonamide, pyridoindole, quinoline carboxylic acid, styrene, sulfinylbenzimidazole, trifluoromethylbenzene, or a combination thereof. In some embodiments, the pharmaceuticalcompound comprises azathioprine, abiraterone, acadesine, adenosine 5' -phosphosulfate,adenosine monophosphate, AICA ribonucleotide, albendazole, amfecloral, aminoglutethimide, aminohippuric acid, amrinone, atazanavir, aztreonam, banoxantrone, binodenoson, bisacodyl, carfilzomib, cefditoren, cefepime, cefmenoxime, cefotaxime, cefpodoxime, ceftazidime, ceftibuten, ceftizoxime, ceftriaxone, coenzyme A, dexlansoprazole, ensulizole, erlotinib, esomeprazole, estazolam, etizolam, etomidate, etoricoxib, etravirine, fiboflapon, flavin adenine dinucleotide, florbetaben (18F), florbetapir (18F), geldanamycin, gentian violet, hexocyclium, idelalisib, implitapide, indium In-111 oxyquinoline, inositol nicotinate, iopodic acid, irbesartan, lansoprazole, levosimendan, loratadine, lornoxicam, losartan, LX-2931, methoxyamine, metyrapone, mifepristone, milrinone, minoxidil, nalidixic acid, niacin, ocinaplon, omeprazole,OSI-930, oxibendazole, oxyquinoline, perampanel, piclidenoson, picosulfuric acid, pitavastatin,porfiromycin, PX-12, pyridoxal, pyridoxal phosphate, rabeprazole, repaglinide, resiquimod, retaspimycin, ridogrel, riluzole, risedronate, rivoglitazone, rosoxacin, S-8510, sapropterin, tecadenoson, tenofovir disoproxil, tenoxicam, thiabendazole, torasemide, triazolam, tucidinostat, ulipristal, varlitinib, vatalanib, verteporfin, verubulin, vidarabine, vipadenant, vorapaxar, or a combination thereof. In some embodiments, the pharmaceutical compound has a pKa of about 5 to about 6. In some embodiments, the pharmaceutical compound comprises a 1,4- benzodiazepine, 1-ribosyl-imidazolecarboxamide, 2-benzimidazolylcarbamic acid ester, 8- hydroxyquinoline, amine, amino acid, peptide, androstane steroid, anilide, aniline and substituted aniline, anthraquinone, aryl thioether, benzodiazine, benzoic acid, beta lactam, biphenyl, bipyridines and oligopyridine, bisphosphonate, diphenylmethane, ether, hexacarboxylic acid, imidazole, imidazoquinoline, indolequinone, naphthyridine, oxosteroid, phenethylamine, phenylbenzimidazole, phenylhydrazine, phenylpiperidine, phenylpyridine,phenylquinoline, pterin, purine ribonucleotide, purines and purine derivative, pyrazolo[1,5 -a]pyrimidine, pyridine carboxaldehyde, pyridinecarboxylic acid, pyridinesulfonamide, pyridoindole, quinoline carboxylic acid, styrene, sulfinylbenzimidazole, trifluoromethylbenzene,Attorney Docket No.: 53160-716.601 or a derivative thereof, or a combination thereof. In some embodiments, the pharmaceutical compound comprises 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, 5- methyltetrahydrofolic acid, abacavir, adefovir dipivoxil, adenine, alprazolam, ALT-2074, amdoxovir, apilimod, adenosine triphosphate, avanafil, axitinib, azelnidipine, benazepril, benzimidazole, bicisate, biricodar dicitrate, brilliant green, cabozantinib, capravirine, carbidopa, cefapirin, cerivastatin, cilazapril, cisplatin, clevidipine, clonixin, clopidogrel, cocarboxylase, dapivirine, delamanid, dersalazine, dolasetron, elbasvir, enalapril, ethionamide, etifoxine, etozoline, famciclovir, felodipine, floctafenine, fominoben, fosaprepitant, GTS-21, hetacillin, imidacloprid, imiquimod, incadronic acid, indibulin, isosulfan blue, isradipine, kinetin, lamotrigine, ledipasvir, linsitinib, meclinertant, mesalazine, methenamine, moexipril, morniflumate, NADH, nevirapine, nifedipine, niflumic acid, nimodipine, nisoldipine, nitrendipine, olmesartan, pazopanib, peldesine, perindopril, phenelzine, picoplatin, pinacidil, pioglitazone, pipecuronium, pradefovir mesylate, prasugrel, prinomastat, procarbazine, pyridoxine, quinapril, ramipril, rilpivirine, rostaporfin, ruxolitinib, seliciclib, sildenafil, sonidegib, spirapril, stannsoporfin, talmapimod, taribavirin, temocapril, temoporfin, tenofovir alafenamide, thiamine, trandolapril, tropicamide, velpatasvir, ximelagatran, zinc picolinate, zolpidem, or a combination thereof. In some embodiments, the pharmaceutical compound has apKa of about 6 to about 7. In some embodiments, the pharmaceutical compound comprises 1,4 -benzodiazepine, 1-ribosyl-imidazolecarboxamide, 2-benzimidazolylcarbamic acid ester, 8- hydroxyquinoline, amine, amino acid, peptide, androstane steroid, anilide, aniline and substituted aniline, anthraquinone, aryl thioether, benzodiazine, benzoic acid, beta lactam, biphenyl, bipyridines and oligopyridine, bisphosphonate, carbonyl compound, diphenylmethane, ether, hexacarboxylic acid, imidazole, imidazoquinoline, indolequinone, naphthyridine, oxosteroid, phenethylamine, phenylbenzimidazole, phenylhydrazine, phenylpiperidine, phenylpyridine, phenylquinoline, pterin, purine ribonucleotide, purines and purine derivative, pyrazolo[1,5-a]pyrimidine, pyridine carboxaldehyde, pyridinecarboxylic acid, pyridinesulfonamide, pyridoindole, quinoline carboxylic acid, styrene, sulfinylbenzimidazole, trifluoromethylbenzene, or a derivative thereof, or a combination thereof. In some embodiments, the pharmaceutical compound comprises 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, 5- methyltetrahydrofolic acid, abacavir, adefovir dipivoxil, adenine, alprazolam, ALT-2074, amdoxovir, apilimod, avanafil, azelnidipine, benazepril, benzimidazole, bicisate, biricodar dicitrate, brilliant green, capravirine, carbidopa, cerivastatin, cilazapril, cisplatin, clevidipine, clonixin, clopidogrel, cocarboxylase, dapivirine, delamanid, dersalazine, dolasetron, elbasvir, enalapril, etifoxine, etozoline, famciclovir, felodipine, floctafenine, fominoben, fosaprepitant,Attorney Docket No.: 53160-716.601 GTS-21, hetacillin, imidacloprid, imiquimod, incadronic acid, indibulin, isosulfan blue, isradipine, kinetin, lamotrigine, ledipasvir, meclinertant, mesalazine, methenamine, moexipril, morniflumate, nevirapine, nifedipine, niflumic acid, nimodipine, nisoldipine, nitrendipine, olmesartan, pazopanib, peldesine, perindopril, phenelzine, picoplatin, pinacidil, pioglitazone, pipecuronium, pradefovir mesylate, prasugrel, prinomastat, procarbazine, pyridoxine, quinapril, ramipril, rilpivirine, rostaporfin, ruxolitinib, seliciclib, sildenafil, sonidegib, spirapril, stannsoporfin, talmapimod, taribavirin, temocapril, temoporfin, tenofovir alafenamide, thiamine, trandolapril, tropicamide, velpatasvir, ximelagatran, zinc picolinate, zolpidem, acarbose, ajmaline, alcaftadine, alfentanil, alfuzosin, almitrine, amisulpride, amoxicillin, ampicillin, amrubicin, antrafenine, aripiprazole, asenapine, atipamezole, azaperone, bacampicillin, cefaclor, cefadroxil, cefdinir, cefprozil, cephalexin, cephaloglycin, chlordiazepoxide, clozapine, dalfopristin, dasatinib, diethylpropion, domperidone, dorzolamide, doxapram, doxazosin, drotaverine, efinaconazole, eprazinone, flavoxate, flibanserin, flupirtine, imidafenacin, indinavir, ketamine, ketotifen, lapatinib, loxapine, mepivacaine, methacycline, moxonidine, nefazodone, oftasceine, olanzapine, ondansetron, phendimetrazine, pivampicillin, pramocaine, prazosin, quetiapine, ranolazine, rupatadine, setiptiline, terazosin, tetrabenazine, ticlopidine, tizanidine, tofacitinib, trazodone, trimethoprim, valaciclovir, valganciclovir, ziprasidone, or a combination thereof.

[0005] In some embodiments, the pharmaceutical compound has a pKa of about 7 to about 8. In some embodiments, the pharmaceutical compound comprises an ajmaline-sarpagine alkaloid, 1,4-benzodiazepine, 2,3,5-trisubstituted thiophene, alcohols and polyol, amine, amino acid or peptide, anilide, anisole, benzazepine, benzazocine, benzene, benzimidazole, benzocycloheptapyridine, benzodiazepine, benzodiazine, benzofuran, benzoic acid, benzothiadiazole, benzothiazepine, benzotriazole, benzoxazepine, benzoxepine, benzylamine, benzylisoquinoline, benzylpiperidine, beta lactam, biphenyl, carbazole, carbohydrate, carbonyl compound, carboxylic acid, cycloheptathiophene, diarylheptanoid, diazanaphthalene, diazinane, diazine, dibenzocycloheptene, dibenzodiazepine, dibenzothiazepine, dibenzoxazepine, dibenzoxepine, diphenylmethane, ergolin, flavone, flavonoid, halobenzene, hybrid peptide, hydropyridine, indane, indole, indoline, isoquinoline, isoquinolone, lactam, lineardiarylheptanoid, lysergic acid, macrolactam, macrolide lactam, monoterpenoid, morpholine, n -acylpiperidine, n-alkylindole, naphthacene, naphthopyranone, naphthopyran, n-phenylurea, organonitrogen compound, organooxygen compound, oxazinane, pentacarboxylic acid, peptidomimetic, phenanthrene, phenethylamine, phenol ether, phenylmethylamine, phenylpiperidine, phenyltropane, piperazine, piperidinecarboxylic acid, piperidine, polypeptide,Attorney Docket No.: 53160-716.601prenol lipid, pyridazines and derivative, pyridine, pyrimidine 2' -deoxyribonucleoside,pyrimidine nucleoside, pyrimidine, quinoline carboxylic acid, quinoline, steroid ester, steroid, tetracenequinone, tetracycline, tetrahydroisoquinoline, thienopyridine, thiophene, tropane alkaloid, xylene, yohimbine alkaloid, or derivatives thereof, or a combination thereof. In some embodiments, the pharmaceutical compound comprises acarbose, ajmaline, alcaftadine, alfentanil, alfuzosin, alizapride, almitrine, almorexant, altretamine, altropane, alvocidib, amdinocillin, aminolevulinic acid, amisulpride, amoxicillin, ampicillin, amrubicin, antrafenine, aripiprazole, asenapine, atipamezole, AV-412, azaperone, azatadine, bacampicillin, barnidipine, benidipine, bifeprunox, bleomycin, blonanserin, bradanicline, brifentanil, bupivacaine, buspirone, cariporide, cariprazine, casopitant, cathinone, cefaclor, cefadroxil, cefdinir, cefprozil, cefradine, cephalexin, cephaloglycin, cethromycin, cetirizine, chlorcyclizine, chlordiazepoxide, chlortetracycline, cilansetron, clozapine, dalfopristin, dapiprazole, dasatinib, deserpidine, diethylpropion, domperidone, dorzolamide, dovitinib, doxapram, doxazosin, doxycycline, drotaverine, edonerpic, efinaconazole, elsamitrucin, eluxadoline, enalaprilat, enzastaurin, eprazinone, ergonovine, ergotamine, EVT-101, ezatiostat, facinicline, fenproporex, finafloxacin, flavoxate, flibanserin, flunarizine, flupirtine, hexaminolevulinate, hydroxyzine, iclaprim, iloperidone, imidafenacin, indinavir, josamycin, ketamine, ketotifen, lapatinib, larazotide, lesopitron, levobupivacaine, levocetirizine, lidocaine, linaclotide, lofexidine, loracarbef, lorpiprazole, loxapine, lysergic acid diethylamide, manidipine, mepiprazole, mepivacaine, methacycline, methyl aminolevulinate, methylergometrine, methysergide, miglitol, motesanib, moxonidine, naloxone, naluzotan, nefazodone, netupitant, oftasceine, olanzapine, onalespib, ondansetron, oxytetracycline, palonosetron, perospirone, phendimetrazine, phenoxybenzamine,pirenzepine, pivampicillin, pivmecillinam, pizotifen, pramocaine, prazosin, priralfinamide, prx -08066, pyrimethamine, quetiapine, RAF-265, raloxifene, ranolazine, reboxetine, remifentanil, rescinnamine, reserpine, rifampicin, rifapentine, rocuronium, ropivacaine, rupatadine, safinamide, saxagliptin, setiptiline, SNX-5422, solithromycin, sufugolix, SUVN-502, talactoferrin alpha, telithromycin, terazosin, tetrabenazine, ticlopidine, tipifarnib, tizanidine, tofacitinib, trabectedin, trazodone, trimethoprim, trimetrexate, tymazoline, valaciclovir, valganciclovir, valomaciclovir, valtorcitabine, venetoclax, voglibose, yohimbine, ziprasidone, zosuquidar, or a combination thereof. In some embodiments, the pharmaceutical compound hasa pKa of about 8 to about 9. In some embodiments, the pharmaceutical compound comprises 1 -benzopyran, 1-benzothiopyran, 1-phenyltetrahydroisoquinoline, alcohol, polyol, amine, amino acid, peptide, aminoquinoline and derivative, androstane steroid, anilide, anisole, aryl thioether, benzenediol, benzenesulfonamide, benzo-1,4-dioxane, benzodiazine, benzoic acid andAttorney Docket No.: 53160-716.601 derivative, benzoquinoline, benzylamine, benzylether, benzylpiperidine, beta lactam, biphenyl and derivative, carbazole, carbohydrate and carbohydrate conjugate, carbonyl compound, carboxylic acid derivative, depsipeptide, dibenzazepine, dibenzothiepin, dibenzoxazepine, diphenylacetonitrile, diphenylfuran, diphenylmethane, ether, fatty acid and conjugate, fentanyl, galanthamine-type amaryllidaceae alkaloid, halobenzene, hydropyridine, imidazolidine, indazole, indole, indoloquinoline, isoquinolone and derivative, isoxazoline, lysergic acid and derivative, methoxybenzene, monoterpenoid, morpholine, n-alkylindole, naphthyridine, oxadiazole, pentacarboxylic acid and derivative, phenethylamine, phenothiazine, phenoxazine, phenoxy compound, phenylmethylamine, phenylnaphthalene, phenylpiperidine, phenylpropane,phenylpyridine, phenylpyrrolidine, phenylquinoline, piperazine, piperidinecarboxylic acid andderivative, purine, pyrimidine and pyrimidine derivative, pyrrolidinylpyridine, quinoline carboxamide, quinoline carboxylic acid, styrene, substituted pyrrole, sulfanilide, tetracarboxylic acid and derivative, thiazole, thiophene carboxylic acid and derivative, trifluoromethylbenzene, xylene, or a derivative thereof, or a combination thereof. In some embodiments, the pharmaceutical compound comprises aceprometazine, acetophenazine, aclarubicin, acrivastine, afatinib, afimoxifene, alanosine, amiodarone, ammonia n-13, ammonium molybdate, amonafide, amorolfine, amoxapine, amsacrine, amylocaine, anamorelin, anileridine, aplindore, apraclonidine, articaine, arzoxifene, asimadoline, aspartame, astemizole, atrasentan, azelastine, azimilide, bedaquiline, benzylfentanyl, bosutinib, brexpiprazole, brimonidine, bromodiphenhydramine, buclizine, budiodarone, bupivacaine, bupropion, butyrfentanyl, caldaret, captodiame, carbinoxamine, carfentanil, carvedilol, cefminox, cefotiam, celgosivir, cevimeline, chlorcyclizine, chloroprocaine, chloropyramine, chlorotoxin I-131, cinnarizine, ciprofloxacin, cisapride, clarithromycin, clofedanol, clomocycline, clonidine, cloperastine, CNS- 5161, cocaine, cyclacillin, cyclizine, cyclopentolate, cycloserine, cyproheptadine, darapladib, daunorubicin, DDP-225, demeclocycline, deramciclane, desvenlafaxine, dicyclomine, dihydroergotamine, diltiazem, dimenhydrinate, dimetotiazine, diphenhydramine, diphenoxylate,diphenylpyraline, dofetilide, donepezil, dotarizine, doxorubicin, doxylamine, droxid opa, d-serine, dyclonine, edetic acid, edivoxetine, elacridar, eletriptan, eliglustat, emedastine, enoxacin, eperisone, epinastine, epinephrine, epirubicin, erythromycin, ethoheptazine, famotidine, fasudil, fentanyl, flupentixol, fluphenazine, flurazepam, forodesine, friulimicin B, gaboxadol, gadoversetamide, galantamine, garenoxacin, gatifloxacin, glesatinib, glucosamine, glypromate, granisetron, grepafloxacin, haloperidol, hydrocodone, hydromorphone, idarubicin, imatinib, imolamine, indium In-111 pentetate, iroxanadine, isoaminile, isoprenaline, isothipendyl, isoxsuprine, istaroxime, itopride, ketobemidone, lasofoxifene, l-asparagine, levobupivacaine,Attorney Docket No.: 53160-716.601 levonordefrin, lincomycin, lobeline, lofentanil, lomefloxacin, l-threonine, lucanthone, lumateperone, lurasidone, LY-517717, managlinat dialanetil, masitinib, meclizine, melperone, mepyramine, mequitazine, mesoridazine, methdilazine, midodrine, migalastat, miglustat,mimosine, minocycline, moxisylyte, naloxegol, nebivolol, nelfinavir, nicardipine, nicergoline,nicotine, norepinephrine, norfloxacin, normethadone, ocaperidone, ohmefentanyl, orphenadrine, osimertinib, oxybuprocaine, oxybutynin, oxycodone, oxyphencyclimine, pafuramidine, palbociclib, paliperidone, paliroden, pargyline, PBT-1033, pelitinib, pentetate calciumtrisodium, pentetate zinc trisodium, pentostatin, perphenazine, pethidine, p -fluorofentanyl,phenindamine, phenmetrazine, phenyltoloxamine, pimavanserin, pimozide, pipamperone, pipazethate, pipendoxifene, pipotiazine, pirlindole, ponatinib, PPI-1019, prilocaine, procaine, prochlorperazine, proflavine, proparacaine, propericiazine, propiomazine, propoxycaine, protokylol, prucalopride, PRX-07034, quinagolide, quinupristin, rabeximod, ranitidine, rasagiline, remacemide, remoxipride, renzapride, rifabutin, rifalazil, rilapladib, risperidone, rivastigmine, robalzotan, rolapitant, rolitetracycline, roxatidine acetate, saquinavir, sarafloxacin, sarizotan, selegiline, serine, sertindole, sincalide, sitagliptin, solifenacin, sparfloxacin, spinosad, sufentanil, sulpiride, tacrine, talabostat, tamoxifen, tariquidar, technetium tc-99m tetrofosmin, tegaserod, terbinafine, terconazole, tetracaine, tetracycline, tetrofosmin, thienylfentanyl, thioproperazine, thioridazine, thiothixene, thonzylamine, tianeptine, tigecycline, tocainide, tolperisone, toremifene, trifluoperazine, trimebutine, trimethobenzamide, tripelennamine, triprolidine, tromethamine, tubocurarine, udenafil, vanoxerine, veliparib, venlafaxine, vicriviroc, vilazodone, viloxazine, vinblastine, vincristine, vindesine, vinorelbine, voacamine, vortioxetine, xaliproden, xanthinol, zanapezil, zotepine, zuclopenthixol, α-methylfentanyl, α- methylthiofentanyl, β-hydroxythiofentanyl, or a combination thereof. In some embodiments, the pharmaceutical compound has a pKa of about 9 to about 10. In some embodiments, the pharmaceutical compound comprises a 1-benzopyran, 1-benzothiopyran, 1-hydroxy-4- unsubstituted benzenoid, 4-quinolinemethanol, 5’-deoxy-5’-thionucleoside, amine, amino acid, peptide, aminophenyl ether, aminoquinoline, anilide, anisole, anthraquinone, benzenediol, benzenesulfonamide, benzo-1,4-dioxane, benzodiazine, benzoic acid, benzonitrile, benzoquinoline, benzoxazinone, benzoyl, benzyl alcohol, benzylether, benzylpiperidine, beta lactam, biphenyl, bisphosphonate, carbazole, carbohydrate and carbohydrate conjugate, cytisine, depsipeptide, dibenzazepine, dibenzothiepin, dibenzoxepine, dicarboxylic acid, diphenylacetonitrile, diphenylmethane, diterpenoid, ether, fentanyl, glycerophosphoserine, halobenzene, hybrid peptide, hydropyridine, hydroquinoline, hydroxypyridine, indazole, indolecarboxylic acid, indole, indoline, indoloquinoline, indolyl carboxylic acid, isoquinolineAttorney Docket No.: 53160-716.601quinone, lysergic acid, methoxybenzene, naphthyridine, nitrobenzene, nitroquinoline,organosulfonic acid, pentacarboxylic acid, phenethylamine, pheniramine, phenothiazine, phenoxazine, phenoxy compound, phenoxyacetic acid, phenylacetamide, phenylbutylamine, phenylmethylamine, phenylpiperidine, phenylpropane, phenyltropane, piperazine, piperidinecarboxylic acid, pregnane steroid, purines and purine, pyridinium, quinoline carboxylic acid, quinolone, steroid ester, styrene, substituted pyrrole, sulfanilide, tametraline, thiophene carboxylic acid, toluene, trifluoromethylbenzene, tryptamine, tyrosol, or a derivative thereof, or a combination thereof. In some embodiments, the pharmaceutical compound comprises (3S)-3-methyl-D-aspartic acid, isoxsuprine, 13-deoxydoxorubicin, 3-allylfentanyl, 3- methylfentanyl, 4-phenylfentanyl, 7-hydroxystaurosporine, acebutolol, ademetionine, aldoxorubicin, alendronic acid, alethine, alimemazine, aliskiren, almotriptan, alogliptin, alprenolol, ambroxol, amibegron, amikacin, amineptine, aminocandin, amitriptyline, amlodipine, amphotericin b, antazoline, apramycin, aprindine, arbaclofen, arbekacin, arbutamine, arformoterol, arimoclomol, arotinolol, arylacenamide, atenolol, atomoxetine, atosiban, atropine, azithromycin, bacitracin, baclofen, bambuterol, bazedoxifene, becatecarin, benfluorex, benzatropine, benzphetamine, benzydamine, benzylpenicilloyl polylysine, bepotastine, bepridil, besifloxacin, betahistine, betaxolol, betazole, bevantolol, bilastine, bimoclomol, biperiden, bisoprolol, bopindolol, brasofensine, bromhexine, bromopride, brompheniramine, bufuralol, bupranolol, butenafine, cabergoline, canfosfamide, carbocisteine, carteolol, caspofungin, cediranib, ceforanide, ceftolozane, celiprolol, chlorphenamine, chlorpromazine, chlorprothixene, cilastatin, cinchocaine, cinitapride, citalopram, clemastine, clenbuterol, clocapramine, clofazimine, clomifene, clomipramine, cobimetinib, codeine, colestipol, CP-122721, cyamemazine, cyclobenzaprine, cycrimine, cystine, cytisine, dalbavancin, dapoxetine, daptomycin, darinaparsin, declopramide, demexiptiline, desloratadine, dexbrompheniramine, dexchlorpheniramine maleate, dexmethylphenidate, dextromethorphan, dextropropoxyphene, dextrothyroxine, dezocine, difenoxin, dihydrocodeine, dimetacrine, dimetindene, diphenidol, dipivefrin, diprenorphine, dirithromycin, D-methionine, dobutamine, dopamine, doripenem, dosulepin, doxepin, dronedarone, duloxetine, encainide, enclomiphene, ephedrine, epicept NP-1, eribulin, ertapenem, escitalopram, esmolol, ethambutol, ethopropazine, ethylmorphine, etidocaine, etryptamine, fenoterol, fenspiride, ferrous bisglycinate, fexofenadine, filanesib, fingolimod, flecainide, fluoxetine, fluspirilene, fluvoxamine, formoterol, framycetin, gabapentin, gadobenic acid, gadofosveset trisodium, gadopentetate dimeglumine, gadoteridol, gadoxetic acid, gemifloxacin, glutamic acid, glutathione, glutathione disulfide, glycine, golotimod, gosogliptin, granisetron, halofuginone, heroin, hexetidine, hexylcaine, histamine,Attorney Docket No.: 53160-716.601 histidine, homatropine, huperzine A, huperzine B, hydroxyamphetamine, hydroxychloroquine, hyoscyamine, ibandronate, ifenprodil, imipramine, indacaterol, ioflupane I-123, irinotecan, isoetarine, ispinesib, ivabradine, K201, kanamycin, labetalol, L-alanine, L-aspartic acid, L- citrulline, L-cysteine, lercanidipine, leukotriene C4, levallorphan, levamlodipine, levobetaxolol, levobunolol, levodopa, levomethadyl acetate, levomilnacipran, levorphanol, levothyroxine, L- glutamine, linagliptin, liothyronine, liotrix, L-isoleucine, LJP 1082, L-leucine, lomitapide, loperamide, L-phenylalanine, L-threonine, L-tryptophan, L-tyrosine, lumefantrine, L-valine, lymecycline, mafenide, magnesium glycinate, mefloquine, melphalan, meropenem, metaraminol, methadone, methadyl acetate, methionine, methotrimeprazine, methoxamine, methyldopa, methylphenidate, metipranolol, metixene, metoclopramide, metoprolol, metyrosine, mexiletine, mibefradil, milnacipran, mirabegron, mitemcinal, mitoxantrone, mn-305, morphine, moxifloxacin, nadolol, naftifine, nalmefene, naratriptan, naronapride, natamycin, nemonoxacin, netilmicin, nitroarginine, NPS-2143, NS-2359, nystatin, oglufanide, olodaterol, olopatadine, omacetaxine mepesuccinate, OPC-28326, orciprenaline, osanetant, oseltamivir, oxamniquine, oxilofrine, oxitriptan, oxprenolol, pamidronate, paromomycin, paroxetine, penbutolol, penicillamine, pentoxyverine, pergolide, phenaridine, phenindamine, pheniramine, phentolamine, phenylephrine, phenylpropanolamine, pholcodine, phosphatidyl serine, piboserod, pindolol, piperazine, pirarubicin, pirbuterol, pixantrone, polaprezinc, pracinostat, practolol, procainamide, procaterol, procyclidine, promazine, promethazine, propafenone, propoxyphene napsylate, propranolol, PRX-03140, pseudoephedrine, PX-478, quarfloxin,quinidine, quinidine barbiturate, quinine, repinotan, retapamulin, ribostamycin, ritodrine,rizatriptan, ronacaleret, roxithromycin, salbutamol, salmeterol, saredutant, selenomethionine, seproxetine, serotonin, sertraline, sibutramine, silodosin, siramesine, solabegron, sotalol, spectinomycin, spiramycin, sumanirole, sumatriptan, sunitinib, tamsulosin, tandutinib, tapentadol, TAS-108, taurine, tedisamil, telavancin, terbutaline, terfenadine, tesmilifene, tesofensine, tetrodotoxin, TG-100801, tiagabine, ticalopride, tilmicosin, timolol, tobramycin, topotecan, tramadol, tranylcypromine, triethylenetetramine, triflupromazine, trihexyphenidyl, trimetazidine, trimipramine, trovafloxacin, tyramine, ubenimex, vancomycin, vandetanib, varenicline, vecuronium, verapamil, vernakalant, vigabatrin, vilanterol, vildagliptin, zolmitriptan, α-methylacetylfentanyl, α-methylfentanyl, β-methylfentanyl, or a combination thereof. In some embodiments, the pharmaceutical compound has a pKa of about 10 to about 13. In some embodiments, the pharmaceutical compound comprises 2,6-dimethyl-3-benzazocine, alkaline earth metal oxide, alkylthiol, amine, amino acid, peptide, aminopyridine, aminoquinoline, benzenediol, benzoic acid, benzoquinoline, beta lactam, bile acid, alcohol,Attorney Docket No.: 53160-716.601 biphenyl, bisphosphonate, carbazole, carbohydrates and carbohydrate conjugate, carboxylic acid derivative, cyclohexylamine, depsipeptide, dibenzazepine, diphenylmethane, ether, fatty acids and conjugate, guanidine, halobenzene, hybrid peptide, indolecarboxylic acid, indole, indoline, monoterpenoid, n-arylamide, organosulfonic acid, peptoid-peptide hybrid, phenethylamine, pheniramine, phenylbutylamine, phenylmethylamine, phenylpiperidine, phenylpropane, phenylpropylamine, phenylpyridine, piperidinecarboxylic acid, purines and purine derivative, pyrazolylpyridine, pyrimidines and pyrimidine derivative, tetracarboxylic acid, tryptamine, urea, xylene, or a derivative thereof, or a combination thereof. In some embodiments, the pharmaceutical compound comprises 2-iminobiotin, abarelix, ABT-510, afamelanotide, agmatine, alverine, alvimopan, amantadine, AMD-070, amifostine, aminocaproic acid, amodiaquine, amphetamine, anatibant, apomorphine, argatroban, arverapamil, atiprimod, aviptadil, bedoradrine, benzoctamine, bethanidine, bicifadine, bivalirudin, brostallicin, buformin, buprenorphine, butorphanol, butriptyline, capreomycin, carbamide peroxide, ceftobiprole, ceritinib, cetrorelix, chlorhexidine, chloroquine, chlorphentermine, cinacalcet, corticorelin ovine triflutate, cr665, creatine, crizotinib, cysteamine, CZEN 002, dalfampridine, darifenacin, debrisoquin, deferoxamine, degarelix, delcasertib, denibulin, desipramine, deslorelin, desmopressin, dexfenfluramine, dextroamphetamine, diethylnorspermine, dihydrostreptomycin, disopyramide, eflornithine, enviomycin, etorphine, felypressin, fencamfamine, fenethylline, fenfluramine, fenoldopam, fesoterodine, fradafiban, frovatriptan, fursultiamine, gadoteric acid, gadoteridol, gamma-aminobutyric acid, ganirelix, gentamicin, gonadorelin, goserelin, guanadrel, guanethidine, guanidine, halofantrine, hexoprenaline, histrelin, hydroxyproline, hydroxystilbamidine isethionate, ibutilide, icatibant, imipenem, indalpine, indecainide, iobenguane, iobenguane sulfate I-123, isometheptene, labradimil, L- aminocarnityl-succinyl-leucyl-argininal-diethylacetal, lanreotide, L-arginine, L-eflornithine, levmetamfetamine, levocabastine, lisdexamfetamine, lisinopril, lixisenatide, L-lysine, lorcaserin, L-proline, magnesium oxide, maprotiline, maraviroc, mecamylamine, memantine, mephentermine, metformin, methamphetamine, midomafetamine, nafarelin, nalbuphine, naltrexone, naphazoline, neramexane, neridronic acid, nintedanib, nor-noha, nortriptyline, nylidrin, obinepitide, octreotide, olcegepant, oritavancin, ornithine, otamixaban, oxymetazoline, oxymorphone, panobinostat, pasireotide, pemetrexed, pentamidine, pentazocine, peramivir, perhexiline, phencyclidine, phenformin, phentermine, pimagedine, piracetam, plerixafor, polymyxin B sulfate, pozanicline, pramipexole, pregabalin, prezatide, primaquine, progabide, proguanil, propylhexedrine, protriptyline, pyrantel, quinacrine, ramoplanin, rifaximin, rimantadine, rivanicline, romidepsin, ropinirole, rotigotine, saralasin, satraplatin, serotonin,Attorney Docket No.: 53160-716.601 SGS-742, sitamaquine, SNS-032, somatostatin, spermine, SQ-109, squalamine, streptomycin, T131, tafenoquine, talotrexin, tanespimycin, tecastemizole, tenocyclidine, terlipressin, tesamorelin, tetracosactide, tetryzoline, tezampanel, tipiracil, tirofiban, tolazoline, tolterodine, tramiprosate, tranexamic acid, triptorelin, ularitide, urea C-13, vapitadine, vintafolide, viomycin, WX-UK1, xylometazoline, zanamivir, or a combination thereof. In some embodiments, the pharmaceutical composition is a solid. In some embodiments, the pharmaceutical compound has a pKa of at least 2. In some embodiments, the pharmaceutical compound has a pKa of about 2 to about 7.5. In some embodiments, the pharmaceutical compound has a pKa of about 1 to about 5. In some embodiments, the pharmaceutical compound has a pKa of about 7.5 to about 11,In some embodiments, the pharmaceutical composition is formulated as a liquid. In some embodiments, the pharmaceutical compound has a pKa of at least 5. In some embodiments, the pharmaceutical compound has a pKa of about 5 to about 7. In some embodiments, the pharmaceutical composition when formulated as a solution has a lower osmolality than a solution comprising the composition comprising a salt of the pharmaceutical compound and a salt of the complexing agent. In some embodiments, the pharmaceutical composition improves a solubility of the pharmaceutical compound by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or about 100% as compared to a composition (i) without the complexing agent or (ii) wherein the pharmaceutical compound does not complex with one of more of the acidic functional groups of the complexing agent. In some embodiments, the pharmaceutical composition improves a solubility of the pharmaceutical compound by about 2-fold, about 3-fold, about 4-fold, about 5-fold, about 6-fold, about 7-fold, about 8-fold, about 9-fold, about 10-fold, about 20-fold, about 30-fold, about 40-fold, or about 50-fold as compared to a composition (i) without the complexing agent or (ii) wherein the pharmaceutical compound does not complex with one of more of the acidic functional groups of the complexing agent. In some embodiments, the complexing agent comprises a substituted cyclodextrin. In some embodiments, the complexing agent comprises a cyclodextrin substituted with at least one acidic functional group. In some embodiments, the cyclodextrin is substituted with 3 to 8 acidic functional groups. In some embodiments, the cyclodextrin is sulfobutylether- β-cyclodextrin (SBEBCD). In some embodiments, the pharmaceutical composition when formulated as a solution has a lower osmolality than a solution comprising a composition comprising a salt of the pharmaceutical compound and a salt of the complexing agent. In some embodiments, the pharmaceutical is formulated for subcutaneous, intramuscular, sublingual, oral, rectal, transvaginal, or intranasal administration. In some embodiments, the pharmaceutical composition when formulated as a solution has an osmolality of no more than about 850Attorney Docket No.: 53160-716.601 mOsm / kg. In some embodiments, the pharmaceutical composition has a pH of about 4 to about 7. In some embodiments, the complexing agent is present in an amount of about 10 mg / mL to about 600 mg / mL. In some embodiments, the complexing agent acts as the counterion tobetween 1 to 10 molecules of the pharmaceutical compound. In some embodiments, thecomplexing agent further comprises a non-polar pore. In some embodiments, the pharmaceutical composition further comprises an additional molar equivalent of the pharmaceutical compound, wherein the additional molar equivalent of the pharmaceutical compound is unionized and complexed to the non-polar pore. In some embodiments, the ratio of complexing agent to the pharmaceutical compound is about 1:1.1. In some embodiments, the ratio of complexing agent to the pharmaceutical compound is about 1:2. In some embodiments, the ratio of complexing agent to the pharmaceutical compound is about 1:3. In some embodiments, the ratio of complexing agent to the pharmaceutical compound is about 1:4. In some embodiments, the ratio of complexing agent to the pharmaceutical compound is about 1:5. In some embodiments, the ratio of complexing agent to the pharmaceutical compound is about 1:6.5. In some embodiments, the pharmaceutical compound has a solubility of less than about 50 mg / ml as salt in an aqueous medium. In some embodiments, the pharmaceutical compound has a solubility of less than about 10 mg / ml as salt in an aqueous medium. In some embodiments, the pharmaceutical compound has a solubility of less than about 5 mg / ml as salt in an aqueous medium. In some embodiments, the pharmaceutical compound has a solubility of less than about 0.5 mg / ml as salt in an aqueous medium. In some embodiments, the pharmaceutical compound has a solubility of less than about 0.1 mg / ml as salt in an aqueous medium. In some embodiments, the pharmaceutical compound is ionized. In some embodiments, the pharmaceutical compound comprises rotigotine, eletriptan, DXM, midazolam, remdesivir, copanlisib, melevodopa, tigecycline, naloxone, amikacin, 1-amantadine, 2-amantadine, rimantadine, amifampridine, rapamycin, clonidine, morphine, hydrocodone, sumatriptan,ropivacaine, bupivacaine, diphenhydramine, granistetron, deschloroketamine, 2 -fluoro-deschloroketamine, or caspofungin. In some embodiments, the pharmaceutical compound comprises a GABA-ergic. In some embodiments, the GABA-ergic comprises Baclofen, Gaboxidol, or Muscimol, or a combination thereof. In some embodiments, the pharmaceutical compound comprises an alpha-2 agonist. In some embodiments, the alpha-2 agonist comprises Clonidine, Guanfacine, or Tizanidine, or a combination thereof. In some embodiments, the pharmaceutical compound is an ophthalmic. In some embodiments, the ophthalmic comprises aceclidine, atropine, azelastine, brimonidine, cyclopentolate, ketotifen, levobunolol, olopatadine, pilocarpine, proparacaine, tetracaine, timolol, or tropicamide. In some embodiments, theAttorney Docket No.: 53160-716.601 pharmaceutical compound is a bisphosphonate. In some embodiments, the bisphosphonate is alendronate, ibandronate, pamidronate, risedronate, zoledronic acid, or a combination or two or more thereof. In some embodiments, the pharmaceutical compound is an antibiotic. In some embodiments, the antibiotic comprises amikacin, amoxicillin, ampicillin, azithromycin, aztreonam, cefaclor, cefadroxil, cefalexin, cefazolin, cefdinir, cefditoren, cefepime, cefiderocol, cefixime, cefmetazole, cefoperazone, cefotaxime, cefotetan, cefovecin, cefoxitin, cefpodoxime, cefprozil, ceftaroline, ceftazidime, ceftibuten, ceftizoxime, ceftolozane, ceftriaxone, cefuroxime, cephalexin, cephalothin, cephapirin, cephradine, ciprofloxacin, clarithromycin, clindamycin, colistin, dalbavancin, dalfopristin, daptomycin, doripenem, doxycycline, ertapenem, eravacycline, erythromycin, fosfomycin, gentamicin, imipenem, kanamycin, lefamulin, levofloxacin, linezolid, lincomycin, meropenem, metronidazole, minocycline, moxifloxacin, nalidixic acid, neomycin, nitrofurantoin, oritavancin, penicillin, piperacillin, polymyxin B, quinupristin, retapamulin, rifampicin, streptomycin, sulfacetamide, sulfadiazine, sulfamethizole, sulfamethoxazole, sulfasalazine, sulfisoxazole, teicoplanin, telavancin, tetracycline, tigecycline, tobramycin, trimethoprim, or vancomycin, or a combination thereof. In some embodiments, the pharmaceutical compound is an anticoagulant or a thrombolytic. In some embodiments, the anticoagulant or thrombolytic comprises alteplase, argatroban, bivalirudin, fondaparinux, lepirudin, streptokinase, or urokinase, or a combination or two or more thereof. In some embodiments, the pharmaceutical compound is an antifungal. In some embodiments, the antifungal comprises an azole antifungal. In some embodiments, the antifungal comprises albendazole, clotrimazole, econazole, fluconazole, isavuconazole, itraconazole, ketoconazole, miconazole, posaconazole, tebuconazole, thiabendazole, or voriconazole, or a combination or two or more thereof. In some embodiments, the antifungal is amphotericin B, anidulafungin, caspofungin, flucytosine, micafungin, natamycin, or voriconazole, or a combination or two or more thereof. In some embodiments, the pharmaceutical compound is an antineoplastic. In some embodiments, the antineoplastic is afatinib, alectinib, alisertib, axitinib, bosutinib, cabozantinib, canertinib, carfilzomib, cediranib, ceritinib, cimicoxib, cobimetinib, dabrafenib, darapladib, dasatinib, delcasertib, dovitinib, erlotinib, etoricoxib, filanesib, glesatinib, ibrutinib, idelalisib, imatinib, ispinesib, ixazomib, lapatinib, lenvatinib, linsitinib, lonafarnib, masitinib, motesanib, nilotinib, nintedanib, odanacatib, olaparib, onalespib, osimertinib, palbociclib, pazopanib, pelitinib, ponatinib, regorafenib, rilapladib, ruxolitinib, seliciclib, sonidegib, sorafenib, sunitinib,tandutinib, tipifarnib, tofacitinib, vandetanib, varlitinib, varlitinib, vatalanib, velipa rib,vemurafenib, vismodegib, or a combination or two or more thereof. In some embodiments, the pharmaceutical compound is an antiviral. In some embodiments, the antiviral comprisesAttorney Docket No.: 53160-716.601 abacavir, acyclovir, adefovir, amantadine, amprenavir, atazanavir, bictegravir, cidofovir, darunavir, dasabuvir, delavirdine, didanosine, dolutegravir, efavirenz, elvitegravir, emtricitabine, enfuvirtide, entecavir, famciclovir, foscarnet, ganciclovir, grazoprevir, imiquimod, indinavir, lamivudine, laninamivir, ledipasvir, lopinavir, maraviroc, nelfinavir, nevirapine, ombitasvir, oseltamivir, paritaprevir, penciclovir, peramivir, plerixafor, podofilox, raltegravir, ribavirin, rilpivirine, ritonavir, saquinavir, sofosbuvir, stavudine, tenofovir, tipranavir, trifluridine, valaciclovir, valganciclovir, zanamivir, or zidovudine, or a combination thereof. In some embodiments, the pharmaceutical compound comprises a cardiovascular medication. In someembodiments, the cardiovascular medication comprises Bretylium, Dobutamine, Dopexamine,Epoprostenol, Esmolol, Iloprost, Nesiritide, Nitroglycerin, Norepinephrine, or Phenylephrine, or a combination or two or more thereof. In some embodiments, the pharmaceutical compoundcomprises a central nervous system depressant. In some embodiments, the central nervoussystem depressant comprises alprazolam, chlordiazepoxide, clonazepam, diazepam, dexmedetomidine, dextromethorphan, flurazepam, gabapentin, ketamine, lorazepam,midazolam, oxazepam, propofol, temazepam, or triazolam, or a combination or two or morethereof. In some embodiments, the pharmaceutical compound comprises a central nervous system stimulant. In some embodiments, the central nervous system stimulant comprises amphetamine, cocaine, dexmethylphenidate, dextroamphetamine, ephedrine, lisdexamfetamine, methamphetamine, methylphenidate, modafinil, phenylephrine, pseudoephedrine, or sibutramine, or a combination or two or more thereof. In some embodiments, the pharmaceutical compound comprises a local anesthetic. In some embodiments, the local anesthetic comprises articaine, benzocaine, bupivacaine, chloroprocaine, cocaine, dibucaine, etidocaine, levobupivacaine, lidocaine, mepivacaine, prilocaine, procaine, proparacaine, ropivacaine, or tetracaine, or a combination thereof. In some embodiments, the pharmaceutical compound comprises an anti-nausea medicine. In some embodiments, the anti-nausea medicine comprises dolasetron, granisetron, ondansetron, or palonosetron, or a combination thereof. In some embodiments, the pharmaceutical compound is an anti-migraine. In some embodiments, the anti-migraine comprises almotriptan, avitriptan, donitriptan, eletriptan, frovatriptan, lasmiditan, naratriptan, rizatriptan, sumatriptan, or zolmitriptan, or a combination thereof. In some embodiments, the pharmaceutical compound comprises an anti-Parkinson’s medicine. In some embodiments, the anti-Parkinson’s medicine comprises amantadine, apomorphine, benztropine, benserazide, bromocriptine, cabergoline, carbidopa, entacapone, foscarbidopa, foslevodopa, levodopa, melvodopa, pramipexole, rasagiline, ropinirole, rotigotine, safinamide, selegiline, tolcapone, or trihexyphenidyl, or a combination thereof. In some embodiments, theAttorney Docket No.: 53160-716.601 pharmaceutical compound comprises an antihistamine. In some embodiments, the antihistamine comprises acrivastine, brompheniramine, cetirizine, chlorpheniramine, clemastine, cyproheptadine, desloratadine, dexchlorpheniramine, diphenhydramine, doxylamine, fexofenadine, hydroxyzine, levocetirizine, loratadine, meclizine, promethazine, or tripelennamine, or a combination thereof. In some embodiments, the pharmaceutical compound comprises an H2 histamine receptor blocker. In some embodiments, the H2 histamine receptor blocker is cimetidine, famotidine, nizatidine, or ranitidine, or a combination thereof. In some embodiments, the pharmaceutical compound comprises an opioid. In some embodiments, the opioid comprises buprenorphine, butorphanol, codeine, fentanyl, heroin, hydrocodone,hydromorphone, levorphanol, meperidine, methadone, morphine, naloxone , naltrexone,nalmefene, oxycodone, oxymorphone, pentazocine, sufentanil, tapentadol, or tramadol, or a combination or two or more thereof. In some embodiments, the pharmaceutical compound is a tyrosine kinase inhibitor. In some embodiments, the tyrosine kinase inhibitor comprises bosutinib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, ponatinib, sorafenib, or sunitinib or two or more thereof. In some embodiments, the pharmaceutical compound comprises amifampridine, amifostine, aminocaproic acid, argatroban, asenapine, atropine, bivalirudin, cisatracurium, deferoxamine, desmopressin, gabapentin, lurasidone, milrinone, nicotine, octreotide, pregabalin, rocuronium, terbutaline, tirofiban, tranexamic acid, vecuronium, nepafenac, or any combination thereof.

[0006] In some aspects, provided herein are methods of preparing a pharmaceutical composition, comprising combining in a suitable liquid medium: a) a free base form of a pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof, wherein the pharmaceutical compound comprises at least one basic nitrogen atom and a pKa of at least 1; and b) a free acid form of a complexing agent comprising at least one acidic functional group, wherein the molar ratio of the complexing agent to the pharmaceutical compound is from about 1:1 to about 1:10.

[0007] In some aspects, provided herein are methods of treating a disease or disorder comprising administering a pharmaceutical composition as described herein or a pharmaceutically acceptable salt as described herein. BRIEF DESCRIPTION OF THE FIGURES

[0008] FIG.1A shows an example structure of SBEBCD complexed to Na+and H+.

[0009] FIG.1B shows an example of the structure of Tigecycline- SBEBCD salt.

[0010] FIG.2A shows an example of a formulation of Rimantadine HCl being fully dissolved.Attorney Docket No.: 53160-716.601

[0011] FIG.2B shows an example of a formulation of Rimantadine HCl being incompletely dissolved.

[0012] FIG.2C shows an example of the structure of Rimantadine-SBEBCD salt.

[0013] FIG.3A shows an example of undissolved Midazolam SBEBCD-Acid 1:1 ratio relative to H+, as seen by the cloudy solution.

[0014] FIG.3B shows an example of completely dissolved Midazolam SBEBCD-Acid 3:1 ratio relative to cyclodextrin, as seen by the clear solution.

[0015] FIG.3C shows an example of Midazolam SBEBCE-Acid 3:1 salt after lyophilization, crushed into an off-white powder.

[0016] FIG.4 shows an example of the structure of hydrocortisone prodrug-SBEBCD Salt with a non-ionized hydrocortisone prodrug in complexing pore.

[0017] FIG.5A shows images of a solid comprising sodium hydroxide and SBEBCD (Cap) in a 6.5:1 molar ratio post-lyohilization after day 1, subsequently exposed to air after 21 days, and subsequently incubated at 40 °C..

[0018] FIG.5B shows images of a solid comprising sodium hydroxide and SBEBCD (Cap) in a 5:1 molar ratio post-lyohilization after day 1, subsequently exposed to air after 21 days, and subsequently incubated at 40 °C.

[0019] FIG.5C shows images of a solid comprising sodium hydroxide and SBEBCD (Cap) in a 3:1 molar ratio post-lyohilization after day 1, subsequently exposed to air after 21 days, and subsequently incubated at 40 °C.

[0020] FIG.5D shows images of a solid comprising sodium hydroxide and SBEBCD (Cap) in a 1:1 molar ratio post-lyohilization after day 1, subsequently exposed to air after 21 days, and subsequently incubated at 40 °C.

[0021] FIG.5E shows images of a solid comprising SBEBCD (Cap) in a 1:1 molar ratio post- lyohilization after day 1, subsequently exposed to air after 21 days, and subsequently incubated at 40 °C

[0022] FIG.6 illustrates a 6:1 ratio of Ziprasidone (70 mg / mL) SBEBCD-acid on a 5 mL scale after stirring for 1 hour, showing solid stuck to the sides of the vial.

[0023] FIG.7 illustrates a 6:1 ratio of Ziprasidone (70 mg / mL) SBEBCD-acid on a 5 mL scale after stirring for 1 hour, showing solid stuck to the bottom of the vial.

[0024] FIG.8 illustrates a 6:1 ratio of Ziprasidone (70 mg / mL) SBEBCD-acid on a 5 mL scale after stirring for 1 hour, showing solid after scrapping off the sides of the vial and resuspended in solution.Attorney Docket No.: 53160-716.601

[0025] FIG.9 illustrates a 4:1 ratio of Ziprasidone (70 mg / mL) SBEBCD-acid on a 5 mLscale upon initial stirring, showing solid suspended in solution.

[0026] FIG.10 illustrates a 4:1 ratio of Ziprasidone (70 mg / mL) SBEBCD-acid on a 5 mLscale after stirring for 1 hour, showing solid stuck to the sides of the vial.

[0027] FIG.11 illustrates a 4:1 ratio of Ziprasidone (70 mg / mL) SBEBCD-acid on a 5 mLscale after stirring for 1 hour, showing solid stuck to the bottom of the vial.

[0028] FIG.12 illustrates a 4:1 ratio of Ziprasidone (70 mg / mL) SBEBCD-acid on a 5 mL scale after stirring for 1 hour, showing solid after scrapping off the sides of the vial and resuspended in solution.

[0029] FIG.13 illustrates a 70 mg / mL solution of Ziprasidone SBEBCD-acid 4:1 ratio at a volume of 1 mL and stirring for 10 minutes, showing the solid stuck to the sides and bottom of the vial.

[0030] FIG.14 illustrates a 70 mg / mL solution of Ziprasidone SBEBCD-acid 4:1 ratio at a volume of 1 mL and stirring for 10 minutes, showing the clear solution separated from the undissolved solids, which was at pH 0.93.

[0031] FIG.15 illustrates a 14 mg / mL solution of Ziprasidone SBEBCD-acid 4:1 ratio at a volume of 5 mL and stirring for 22 minutes, showing a clear solution and solid stuck to the bottom of the vial, after the solid had been scrapped off of the sides.

[0032] FIG.16 illustrates a 11.7 mg / mL solution of Ziprasidone SBEBCD-acid 4:1 ratio at a volume of 6 mL and stirring for 25 minutes, showing a cloudy solution with small, suspended particles and solid stuck to the bottom of the vial.

[0033] FIG.17 illustrates a 8.75 mg / mL solution of Ziprasidone SBEBCD-acid 4:1 ratio at a volume of 8 mL and stirring for 31 minutes, showing a cloudy tan solution and large solid chunks that were scrapped off of the bottom of the vial.

[0034] FIG.18 illustrates a 7.8 mg / mL solution of Ziprasidone SBEBCD-acid 4:1 ratio at a volume of 9 mL and stirring for 34 minutes, showing the previously scrapped off solid becoming stuck to the bottom again.

[0035] FIG.19 illustrates a 5.4 mg / mL solution of Ziprasidone SBEBCD-acid 4:1 ratio at a volume of 13 mL and stirring for 46 minutes, showing a tan cloudy solution and solid stuck to the bottom and the crease between the bottom and side of the vial.

[0036] FIG.20 illustrates a 5 mg / mL solution of Ziprasidone SBEBCD-acid 4:1 ratio at a volume of 14 mL and stirring for 65 hours, showing a clear solution and solid stuck to the bottom of the vial.Attorney Docket No.: 53160-716.601

[0037] FIG.21 illustrates a 70 mg / mL solution of Ziprasidone SBEBCD-acid 6:1 ratio at a volume of 1 mL and stirring for 10 minutes, showing the solid stuck to the sides and bottom of the vial.

[0038] FIG.22 illustrates a 17.5 mg / mL solution of Ziprasidone SBEBCD-acid 6:1 ratio at a volume of 4 mL and stirring for 19 minutes, showing the solid stuck to the sides and bottom of the vial, and then scrapped off of the sides.

[0039] FIG.23 illustrates a 14 mg / mL solution of Ziprasidone SBEBCD-acid 6:1 ratio at a volume of 5 mL and stirring for 22 minutes, showing small particles suspended in solution and solid stuck to the bottom of the vial.

[0040] FIG.24 illustrates a 7.8 mg / mL solution of Ziprasidone SBEBCD-acid 6:1 ratio at a volume of 9 mL and stirring for 34 minutes, showing large chunks suspended in solution and solid stuck to the bottom of the vial.

[0041] FIG.25 illustrates a 5.4 mg / mL solution of Ziprasidone SBEBCD-acid 6:1 ratio at avolume of 13 mL and stirring for 46 minutes, showing large chunks suspended in solution.

[0042] FIG.26 illustrates a 5 mg / mL solution of Ziprasidone SBEBCD-acid 6:1 ratio at avolume of 14 mL and stirring for 24 hours, showing solid stuck to the bottom of the vial.

[0043] FIG.27 illustrates a table comparing solutions of varying SBEBCD saltconcentrations N=1 (after incubating for 3 weeks) with and without Fehling’s reagent added .DETAILED DESCRIPTION

[0044] Provided herein are, for example, compositions comprising pharmaceutical compound salts with complexing agents as counterions. Such salts are useful in a variety of pharmaceutical compositions, including reduced irritant effect to tissues and / or dermal tissues, subcutaneous, intramuscular, intranasal, and sublingual formulations. In some aspects, use of the salts provided herein in subcutaneous, intranasal, or sublingual formulation is associated with reduced irritanteffect to tissues at the administration site, as well as increased solubility and bioavailability . Incertain aspects, the compositions comprising low molar ratios of pharmaceutical compounds with basic nitrogen atoms to complexing agents are formulated for subcutaneous, sublingual, or intranasal administration. In certain aspects, the compositions comprising prodrug pharmaceutical compounds with basic nitrogen atoms are formulated for subcutaneous, sublingual, or intranasal administration. In certain aspects, the compositions comprising both ionized and unionized pharmaceutical compounds are formulated for subcutaneous, sublingual, or intranasal administration. Also provided herein are, for example, methods of treating, preventing or managing, viral infections, bacterial infections, fungal infections, autoimmuneAttorney Docket No.: 53160-716.601 disorders, inflammatory disorders, depression or opioid overdose, psychiatric disorders, cognitive disorders, neurological disorders, and other various disorders. Definitions

[0045] The abbreviations used herein have their conventional meaning within the chemical and biological arts. The chemical structures and formulae set forth herein are constructedaccording to the standard rules of chemical valency known in the chemical arts.

[0046] Where substituent groups are specified by their conventional chemical formulae, written from left to right, they equally encompass the chemically identical substituents that would result from writing the structure from right to left, e.g., -CH2O- is equivalent to -OCH2-.

[0047] The term “about” as used herein, when referring to a numerical value or range, allows for a degree of variability in the value or range, for example, within 10%, or within 5% of a stated value or of a stated limit of a range. Unless otherwise stated, “about” refers to a degree of variability within 10% of the stated value or of a stated limit of a range.

[0048] The term “pharmaceutical compound” and similar such terms used herein refer to any compound which has the potential to be administered to a subject and may imbue any type of therapeutic benefit to a subject (such as treatment or prevention of a disease, mitigation of symptoms of a disease or condition, or any purpose for which a pharmaceutical or drug can be used). Generally, these compounds will be organic small molecules, though other compounds such as peptides are also considered to be pharmaceutical compounds as used herein. In embodiments, the pharmaceutical compounds will comprise basic nitrogen atoms (e.g., amine groups) which can be protonated upon interaction with an acidic functional group, such as a carboxylic acid or a sulfonic acid. When referring to pharmaceutical compositions, thesecompounds may be referred to generally as “active pharmaceutical ingredient” or “API.” Insome cases, the pharmaceutical compounds herein may simply be referred to as “compounds.”

[0049] The terms “opioid pharmaceutical compound,” “opioid pharmaceutical,” or “opioid,” and similar such terms are all used interchangeably, and the same meaning is meant by each term unless otherwise specified. The term may refer to any naturally occurring opioid or any synthetic homolog or analog. Additionally, any synthetic compound which has similar bioactivity on the opioid receptors of a subject is also intended to be encompassed, as well as any compound which has an opioid antagonist activity (e.g., naltrexone or naloxone). In some cases, the pharmaceutical composition or method for manufacture or use thereof does not include naloxone. When referring to pharmaceutical compositions, these compounds may bereferred to generally as “active pharmaceutical ingredient” or “API.”Attorney Docket No.: 53160-716.601

[0050] As used herein, the terms “comprising,” “comprises,” or the like are used in their typical sense of leaving any claim or embodiment where such language is used able to accommodate additional elements, components, or features. However, it is also contemplated that in each formulation, salt, method, or other disclosure provided herein that uses the term “comprising,” the formulation, salt, method or other disclosure may also be closed to other elements, components, or features as if the term “consisting of” were used in its place. Additionally, it is also contemplated the term “comprising” or similar can also be replaced in thesame manner as if the term “consisting essentially of .”

[0051] A “molar equivalent” as used herein refers to a comparison on the number of moles of a substance compared to the number of moles of another substance and reflects that comparison should be a moles or molarity basis (e.g., the ratio of the moles of one compound to the moles of another). The molar equivalent need not be an integer value. For example, embodiments stating that a pharmaceutical composition comprises a “molar equivalent” of a substance indicates that that the amount of the substance which is present will be measured in some kind of molarity descriptor, such as an additional equivalent of the substance from 0.001 to 100 molar equivalents, or any other range specified herein.

[0052] All percent compositions are given as weight-percentages, unless otherwise stated.

[0053] All average molecular weights of polymers are weight-average molecular weights, unless otherwise specified.

[0054] As used herein, “individual” (as in the subject of the treatment) means both mammals and non-mammals. Mammals include, for example, humans; non-human primates, e.g., apes and monkeys; and non-primates, e.g., dogs, cats, cattle, horses, sheep, and goats. Non-mammals include, for example, fish and birds.

[0055] The terms “disease,” “disorder,” or “condition” refer to a sta te of being or health statusof a patient or subject capable of being treated with the compounds or methods provided herein.The disease may be physical disorder. The disease may be a mental or psychiatric disorder. The disease may be an infection, such as a viral infection, a bacterial infection, or a fungal infection. The disease may be an autoimmune disease. The disease may be a mood disorder. The disease may be an inflammatory disease. The disease may be a brain tumor. The disease may be a neurological condition or disorder. The disease may be migraine headache. The disease may be pancreatitis. The disease may be lymphoma. The disease may be opioid overdose. The disease may be flu infection. In some further instances, “mental or psychiatric disorder” refers to human mental or psychiatric disorders including major depressive disorder, treatment resistant major depressive disorder, Suicidality, Suicidal Ideation, dysthymia, bipolar I disorder, bipolar IIAttorney Docket No.: 53160-716.601 disorder, post-traumatic stress disorder (PTSD), complex trauma, anorexia nervosa, bulimia nervosa, eating disorder NOS, obsessive compulsive disorder, a substance-related disorder (e.g., cannabis dependence or withdrawal, barbiturate dependence or withdrawal, benzodiazepine dependence or withdrawal, amphetamine dependence or withdrawal, opioid dependence or withdrawal, opioid dependence and detoxification, alcohol dependence or withdrawal, cocaine dependence or withdrawal), a pain disorder and an inflammatory disorder, management of pain including but not limited to neuropathic pain, complex regional pain syndrome and post herpetic neuralgia. In some further instances, “neurological disease or disorder” refers to human neurological diseases or disorders including chronic fatigue syndrome, chronic fatigue and immunodeficiency syndrome, neuropathy, fibromyalgia, fibromyalgia syndrome, myalgic encephalomyelitis, migraine, traumatic brain injury (TBI), stroke, dementia, amyotrophic lateral sclerosis, spinal cord injury, shingles, herpes zoster, radiculopathy, polyneuropathy, dyskinesia, dystonia, tinnitus, postherpetic neuralgia, complex regional pain syndrome, central pain syndrome, chronic pain, acute pain, phantom limb syndrome with pain, phantom limb syndrome without pain, myelitis, dysthymia, complex trauma, anorexia nervosa, bulimia nervosa, eating disorder NOS, obsessive compulsive disorder, intermittent explosive disorder, a sleep disorder, a pain disorder or an inflammatory disorder. In some further instances, a brain tumor may be acoustic neuroma, astrocytoma, brain metastases, choroid plexus carcinoma, craniopharyngioma, embryonal tumors, ependymoma, glioblastoma, glioma, medulloblastoma, meningioma, oligodendroglioma, pediatric brain tumors, pineoblastoma, or pituitary tumors. In some instances, the disease, disorder, or condition is one that is associated with substantial or significant pain. In some aspects, the subject is administered the salts of formulations provided herein in order to manage pain. The pain can be associated with a suitable conditions for which an opioid pain management regiment is acceptable. In some aspects, the subject is administered the salts of formulations provided herein in order to treat a brain tumor. In some aspects, the subject is administered the following salts of formulations in order to treat a brain tumor: a pharmaceutical compound with basic nitrogen atoms including a dissociative medication compound, a dissociative hallucinogen compound, a dissociative anesthetic compound, an arylcyclo-hexylamine, a 1,2-diarylethylamine, a keto-arylcyclohexylamine, or a compound that modulates the NMDA receptor, ketamine, a derivative or analog of ketamine, methoxetamine, deschloroketamine, N-ethyl deschloroketamine (eticyclidone), 3-methoxyphencyclidine, methoxieticyclidine, ephenidine, lanicemine, dextromethorphan, dextrorphan, or methoxyketamine.Attorney Docket No.: 53160-716.601

[0056] The expression “effective amount,” when used to describe therapy to an individual suffering from a disorder, refers to the amount of a compound described herein that is effective to inhibit or otherwise act on relevant receptors in the individual’s tissues, wherein such inhibition or other action occurs to an extent sufficient to produce a beneficial therapeutic effect. The effective amount will vary based on the pharmaceutical compound, including but not limited to opioid, or other API used in the formulation and the indication intended to be treated by said compound, including but not limited to opioid, or other API.

[0057] “Substantially” as the term is used herein means completely or almost completely. For example, a composition that is “substantially free” of a component either has none of the component or contains such a trace amount that any relevant functional property of the composition is unaffected by the presence of the trace amount. For example, a compound that is“substantially pure” has only negligible traces of impurities present.

[0058] All chiral, diastereomeric, and / or racemic forms of a structure are intended, unless a particular stereochemistry or isomeric form is specifically indicated. Compounds described herein can include enriched or resolved optical isomers at any or all asymmetric atoms as are apparent from the depictions, at any degree of enrichment. Both racemic and diastereomeric mixtures, as well as the individual optical isomers can be isolated or synthesized so as to be substantially free of their enantiomeric or diastereomeric partners, and these are all within the scope of the present disclosure.

[0059] The inclusion of an isotopic form of one or more atoms in a molecule that is differentfrom the naturally occurring isotopic distribution of the atom in nature is referred to as an“isotopically labeled form” of the molecule. All isotopic forms of atoms are included as options in the composition of any molecule, unless a specific isotopic form of an atom is indicated. For example, any hydrogen atom or set thereof in a molecule can be any of the isotopic forms of hydrogen, e.g., protium (1H), deuterium (2H), or tritium (3H) in any combination. Similarly, any carbon atom or set thereof in a molecule can be any of the isotopic form of carbons, such as11C,12C,13C, or14C, or any nitrogen atom or set thereof in a molecule can be any of the isotopic forms of nitrogen, such as13N,14N, or15N. A molecule can include any combination of isotopic forms in the component atoms making up the molecule, the isotopic form of every atom forming the molecule being independently selected. In a multi-molecular sample of a compound, not every individual molecule necessarily has the same isotopic composition. For example, a sample of a compound can include molecules containing various different isotopic compositions, such as in a tritium or14C radiolabeled sample where only some fraction of the set of molecules making up the macroscopic sample contains a radioactive atom. It is also understood that manyAttorney Docket No.: 53160-716.601 elements that are not artificially isotopically enriched themselves are mixtures of naturally occurring isotopic forms, such as14N and15N,32S and34S, and so forth. A molecule as recited herein is defined as including isotopic forms of all its constituent elements at each position in the molecule. As is well known in the art, isotopically labeled compounds can be prepared by the usual methods of chemical synthesis, except substituting an isotopically labeled precursor molecule. The isotopes, radiolabeled or stable, can be obtained by any method known in the art, such as generation by neutron absorption of a precursor nuclide in a nuclear reactor, by cyclotron reactions, or by isotopic separation such as by mass spectrometry. The isotopic forms are incorporated into precursors as required for use in any particular synthetic route. For example,14C and3H can be prepared using neutrons generated in a nuclear reactor. Following nuclear transformation,14C and3H are incorporated into precursor molecules, followed by further elaboration as needed.

[0060] A “hydrate” is a compound that exists in a composition with water molecules. The composition can include water in stoichiometric quantities, such as a monohydrate or a dihydrate, or can include water in random amounts. As the term is used herein a “hydrate” refers to a solid form, e.g., a compound in water solution, while it may be hydrated, is not a hydrate as the term is used herein.

[0061] A “solvate” is a similar composition except that a solvent other that water replaces the water. For example, methanol or ethanol can form an “alcoholate”, which can again be stoichiometric or non-stoichiometric. As the term is used herein a “solvate” refers to a solid form, e.g., a compound in solution in a solvent, while it may be solvated, is not a solvate as the term is used herein.

[0062] A “prodrug” as is well known in the art is a substance that can be administered to a patient where the substance is converted in vivo by the action of biochemicals within the patient’s body, such as enzymes, to the active pharmaceutical ingredient. Examples of prodrugs include esters of carboxylic acid groups, which can be hydrolyzed by endogenous esterases as are found in the bloodstream of humans and other mammals. Further examples of prodrugs include boronate esters which can be hydrolyzed under physiological conditions to afford the corresponding boronic acid. Conventional procedures for the selection and preparation of suitable prodrug derivatives are described, for example, in “Design of Prodrugs”, ed. H. Bundgaard, Elsevier, 1985.

[0063] In various embodiments, a compound as shown in any of the Examples, or among the exemplary compounds, is provided.Attorney Docket No.: 53160-716.601

[0064] Provisos may apply to any of the disclosed categories or embodiments wherein any one or more of the other above disclosed embodiments or species may be excluded from such categories or embodiments.

[0065] Isomerism in Compounds Described Herein

[0066] Optical Isomerism

[0067] It will be understood that when compounds of the present disclosure contain one or more chiral centers, the compounds may exist in, and may be isolated as pure enantiomeric or diastereomeric forms or as racemic mixtures. The present disclosure therefore includes any possible enantiomers, diastereomers, racemates or mixtures thereof of the compounds described herein.

[0068] The isomers resulting from the presence of a chiral center comprise a pair of non-superimposable isomers that are called “enantiomers.” Single enantiomers of a pure compound are optically active, e.g., they are capable of rotating the plane of plane polarized light. Single enantiomers are designated according to the Cahn-Ingold-Prelog system. The priority of substituents is ranked based on atomic weights, a higher atomic weight, as determined by the systematic procedure, having a higher priority ranking. Once the priority ranking of the four groups is determined, the molecule is oriented so that the lowest ranking group is pointed away from the viewer. Then, if the descending rank order of the other groups proceeds clockwise, the molecule is designated (R) and if the descending rank of the other groups proceeds counterclockwise, the molecule is designated (S). In the example below, the Cahn-Ingold-Prelog ranking is A > B > C > D. The lowest ranking atom, D is oriented away from the viewer.(R) configuration (S) configuration

[0069] The present disclosure is meant to encompass diastereomers as well as their racemic and resolved, diastereomerically and enantiomerically pure forms and salts thereof. Diastereomeric pairs may be resolved by known separation techniques including normal and reverse phase chromatography, and crystallization.

[0070] “Isolated optical isomer” means a compound which has been substantially purified from the corresponding optical isomer(s) of the same formula., the isolated isomer is at least about 80%, more at least 90% pure, even more at least 98% pure, most at least about 99% pure, by weight.Attorney Docket No.: 53160-716.601

[0071] Isolated optical isomers may be purified from racemic mixtures by well-known chiral separation techniques. According to one such method, a racemic mixture of a compound described herein, or a chiral intermediate thereof, is separated into 99% wt.% pure optical isomers by HPLC using a suitable chiral column, such as a member of the series of DAICEL®CHIRALPAK®family of columns (Daicel Chemical Industries, Ltd., Tokyo, Japan). Thecolumn is operated according to the manufacturer’s instructions.

[0072] Certain compounds of the present disclosure possess asymmetric carbon a toms(optical or chiral centers) or double bonds; the enantiomers, racemates, diastereomers, tautomers, geometric isomers, stereoisometric forms that may be defined, in terms of absolute stereochemistry, as (R)-or (S)- or, as (D)- or (L)- for amino acids, and individual isomers are encompassed within the scope of the present disclosure. The compounds of the present disclosure do not include those that are known in art to be too unstable to synthesize and / or isolate. The present disclosure is meant to include compounds in racemic and optically pure forms. Optically active (R)- and (S)-, or (D)- and (L)-isomers may be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. When the compounds described herein contain olefinic bonds or other centers of geometric asymmetry, and unless specified otherwise, it is intended that the compounds include both E and Z geometric isomers.

[0073] As used herein, the term “isomers” refers to compounds having the same number and kind of atoms, and hence the same molecular weight, but differing in respect to the structural arrangement or configuration of the atoms.

[0074] The term “tautomer,” as used herein, refers to one of two or more structural isomers which exist in equilibrium and which are readily converted from one isomeric form to another.

[0075] It will be apparent to one skilled in the art that certain compounds of this disclosure may exist in tautomeric forms, all such tautomeric forms of the compounds being within the scope of the disclosure.

[0076] Unless otherwise stated, structures depicted herein are also meant to include all stereochemical forms of the structure; e.g., the R and S configurations for each asymmetric center. Therefore, single stereochemical isomers as well as enantiomeric and diastereomeric mixtures of the present compounds are within the scope of the disclosure.

[0077] "Alkyl" refers to a straight or branched hydrocarbon chain radical consisting solely ofcarbon and hydrogen atoms, which may optionally be unsaturated with one or more double ortriple bonds, and having from one to fifteen carbon atoms (i.e., C1-C15alkyl). In certain embodiments, an alkyl comprises one to six carbon atoms (i.e., C1-C6alkyl). In certain embodiments, the alkyl group is selected from methyl, ethyl, 1-propyl (n-propyl), 1-methylethylAttorney Docket No.: 53160-716.601 (iso-propyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (iso-butyl), 1,1-dimethylethyl (tert-butyl), 1-pentyl (n-pentyl). The alkyl is attached to the rest of the molecule by a single bond. Unless otherwise specified, the term “alkyl” and its equivalents encompass linear, branched, and / or cyclic alkyl groups. In some instances, an “alkyl” comprises both cyclic and acyclic (linear and / or branched) alkyl components.

[0078] The term “substituted” refers to moieties having substituents replacing a hydrogen on one or more carbons or heteroatoms of the structure. It will be understood that “substitution” or “substituted with” includes the implicit proviso that such substitution is in accordance with permitted valence of the substituted atom and the substituent, and that the substitution results in a stable compound, e.g., which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, etc. As used herein, the term “substituted” is contemplated to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of organic compounds. The permissible substituents may be one or more and the same or different for appropriate organic compounds.

[0079] Substituents may include any substituent, for example, a halogen, a hydroxyl, a carbonyl (such as an oxo (=O), a carboxyl, an alkoxycarbonyl, a formyl, or an acyl), a thiocarbonyl (such as a thioxo (=S), a thioester, a thioacetate, or a thioformate), an alkoxyl, a phosphoryl, a phosphate, a phosphonate, a phosphinate, an amino, an amido, an amidine, an imine, an oximo, a hydrazino, a cyano, a nitro, an azido, a sulfhydryl, an alkyl, an alkylthio, a sulfate, a sulfonate, a sulfamoyl, a sulfonamido, a sulfonyl, an aralkyl, a carbocycle, aheterocycle, a cycloalkyl, a heterocycloalkyl, an aromatic and heteroaromatic moiety .

[0080] As used herein, an “acidic functional group” or similar term (e.g., “acidic functionality”) refers to a chemical moiety which contains at least one dissociable proton (or isotopic variant thereof), or the conjugate base (e.g., the deprotonated anion) of the acidic functional group. In certain embodiments, the dissociable proton dissociates from the chemical moiety at a pH common in aqueous systems (e.g., pHs from about 1 to about 14). In certain embodiments, the dissociable proton dissociates from the chemical moiety in an aqueous system at a pH of less than 7 (e.g., having a pKa value of less than 7, such as a pKa of less than 6, less than 5, less than 4, less than 3, less than 2, or less than 1). As is understood by those in the art, whether an acidic functional group contains the dissociable proton will depend on the conditions of the system in which the chemical moiety is present (e.g., the pH of an aqueous system containing molecule with the acidic functional group or the presence of any base molecule). AsAttorney Docket No.: 53160-716.601 such, the term “acidic functional group” (or reference to a specific acidic functional group such as a carboxylic acid or a sulfonic acid) as used herein is intended to cover the protonated version of the moiety, the deprotonated version of the moiety, and any salt of the moiety, unless otherwise specified.

[0081] Unless otherwise stated, structures depicted herein are also meant to include compounds which differ only in the presence of one or more isotopically enriched atoms (e.g., isotopic variant(s)). For example, compounds having the present structures except for the replacement of a hydrogen by a deuterium or tritium, or the replacement of a carbon by13C- or14C-enriched carbon are within the scope of this disclosure.

[0082] The compounds of the present disclosure may also contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compounds. For example, the compounds may be radiolabeled with radioactive isotopes, such as for example tritium (3H), iodine-125 (125I), or carbon-14 (14C). All isotopic variations of the compounds of the present disclosure, whether radioactive or not, are encompassed within the scope of the present disclosure.

[0083] The terms "a" or "an," as used in herein means one or more. In addition, the phrase "substituted with a[n]," as used herein, means the specified group may be substituted with one or more of any or all of the named substituents. For example, where a group, such as an alkyl or heteroaryl group, is "substituted with an unsubstituted C1-C20alkyl, or unsubstituted 2 to 20 membered heteroalkyl," the group may contain one or more unsubstituted C1-C20alkyls, and / or one or more unsubstituted 2 to 20 membered heteroalkyls.

[0084] A “salt,” as is well known in the art, includes an organic compound such as a carboxylic acid, a sulfonic acid, or an amine, in ionic form, in combination with a counterion. For example, acids in their anionic form can form salts with cations such as metal cations, for example sodium, potassium, and the like; with ammonium salts such as NH4+or the cations of various amines, including tetraalkyl ammonium salts such as tetramethylammonium, or other cations such as trimethylsulfonium, and the like. The terms “pharmaceutically acceptable salts” and / or or “pharmacologically acceptable salts” are meant to include salts of the active compounds that are prepared with relatively nontoxic acids or bases, depending on the particular substituents found on the compounds described herein. When compounds of the present disclosure contain relatively acidic functionalities, base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired base, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amino, or magnesium salt, or aAttorney Docket No.: 53160-716.601 similar salt. When compounds of the present disclosure contain relatively basic functionalities, acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired acid, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include those derived from inorganic acids like hydrochloric, hydrobromic, nitric, carbonic, monohydrogencarbonic, phosphoric, monohydrogenphosphoric, dihydrogenphosphoric, sulfuric, monohydrogensulfuric, hydriodic, or phosphorous acids and the like, as well as the salts derived from relatively nontoxic organic acids like acetic, propionic, isobutyric, maleic, malonic, benzoic, succinic, suberic, fumaric, lactic, mandelic, phthalic, benzenesulfonic, p-tolylsulfonic, citric, tartaric, oxalic, methanesulfonic, and the like. Also included are salts of amino acids such as arginate and the like, and salts of organic acids like glucuronic or galacturonic acids and the like (see, for example, Berge et al., “Pharmaceutical Salts”, Journal of Pharmaceutical Science, 1977, 66, 1- 19). Certain specific compounds of the present disclosure contain both basic and acidic functionalities that allow the compounds to be converted into either base or acid addition salts.

[0085] Thus, the compounds of the present disclosure may exist as salts, such as withpharmaceutically acceptable acids. The present disclosure includes such salts. Non -limitingexamples of such salts include hydrochlorides, hydrobromides, phosphates, sulfates ,methanesulfonates, nitrates, maleates, acetates, citrates, fumarates, propionates, tartrates (e.g., (+)-tartrates, (-)-tartrates, or mixtures thereof including racemic mixtures), succinates, benzoates, and salts with amino acids such as glutamic acid, and quaternary ammonium salts (e.g., methyl iodide, ethyl iodide, and the like). These salts may be prepared by methods known to those skilled in the art.

[0086] The neutral forms of the compounds are regenerated by contacting the salt with a base or acid and isolating the parent compound in the conventional manner. The parent form of the compound may differ from the various salt forms in certain physical properties, such as solubility in polar solvents. In certain embodiments, compounds of the present disclosure contain both basic and acidic functionalities that allow the compounds to be converted into either base or acid addition salts. The neutral forms of the compounds may be regenerated by contacting the salt with a base or acid and isolating the parent compound in a conventional manner. The parent form of the compounds differs from the various salt forms in certain physical properties, such as solubility in polar solvents, but, unless specifically indicated, the salts disclosed herein are equivalent to the parent form of the compound for the purposes of the present disclosure.Attorney Docket No.: 53160-716.601

[0087] In addition to salt forms, the present disclosure provides compounds, which are in a prodrug form. Prodrugs of the compounds described herein are those compounds that readily undergo chemical changes under physiological conditions to provide the compounds of the present disclosure. Prodrugs of the compounds described herein may be converted in vivo afteradministration. Additionally, prodrugs can be converted to the compounds of the presentdisclosure by chemical or biochemical methods in an ex vivo environment, such as, for example, when contacted with a suitable enzyme or chemical reagent.

[0088] Certain compounds of the present disclosure can exist in unsolvated forms as well as solvated forms, including hydrated forms. In general, the solvated forms are equivalent to unsolvated forms and are encompassed within the scope of the present disclosure. Certain compounds of the present disclosure may exist in multiple crystalline or amorphous forms. In general, all physical forms are equivalent for the uses contemplated by the present disclosureand are intended to be within the scope of the present disclosure .

[0089] “Pharmaceutically acceptable excipient” and “pharmaceutically acceptable carrier” refer to a substance that aids the administration of a compound to and absorption by a subject and can be included in the compositions of the present disclosure without causing a significant adverse toxicological effect on the patient. Non-limiting examples of pharmaceutically acceptable excipients include water, NaCl, normal saline solutions, lactated Ringer’s, normal sucrose, normal glucose, complexing agents (e.g., cyclodextrins), binders, fillers, disintegrants, lubricants, coatings, sweeteners, flavors, salt solutions (such as Ringer's solution), alcohols, oils, gelatins, carbohydrates such as lactose, amylose or starch, fatty acid esters, hydroxymethylcellulose, polyvinyl pyrrolidine, and colors, and the like. Such preparations can be sterilized and, if desired, mixed with auxiliary agents such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, coloring, and / or aromatic substances and the like that do not deleteriously react with the compounds of the disclosure. One of skill in the art will recognize that other pharmaceutical excipients are useful in the present disclosure.

[0090] The term "preparation" is intended to include the formulation of the active compound with encapsulating material as a carrier providing a capsule in which the active component with or without other carriers, is surrounded by a carrier, which is thus in association with it. Similarly, cachets and lozenges are included. Tablets, powders, capsules, pills, cachets, andlozenges can be used as solid dosage forms suitable for oral administration.

[0091] The terms “treating” or “treatment” refers to any indicia of success in the therapy or amelioration of an injury, disease, pathology or condition, including any objective or subjectiveAttorney Docket No.: 53160-716.601 parameter such as abatement; remission; diminishing of symptoms or making the injury, pathology or condition more tolerable to the patient; slowing in the rate of degeneration ordecline; making the final point of degeneration less debilitating; improving a pa tient’s physicalor mental well-being. The treatment or amelioration of symptoms can be based on objective or subjective parameters; including the results of a physical examination, neuropsychiatric exams, and / or a psychiatric evaluation. The term "treating" and conjugations thereof, may include prevention of an injury, pathology, condition, or disease. In certain embodiments, treating is preventing. In certain embodiments, treating does not include preventing.

[0092] “Treating” or “treatment” as used herein (and as well-understood in the art) also broadly includes any approach for obtaining beneficial or desired results in a subject’s condition, including clinical results. Beneficial or desired clinical results can include, but are not limited to, alleviation or amelioration of one or more symptoms or conditions, diminishment of the extent of a disease, stabilizing (e.g., not worsening) the state of disease, prevention of a disease’s transmission or spread, delay or slowing of disease progression, amelioration or palliation of the disease state, diminishment of the reoccurrence of disease, and remission, whether partial or total and whether detectable or undetectable. In other words, "treatment" as used herein includes any cure, amelioration, or prevention of a disease. Treatment may prevent the disease from occurring; inhibit the disease’s spread; relieve the disease’s symptoms (e.g., ocular pain, seeing halos around lights, red eye, very high intraocular pressure), fully or partially remove the disease’s underlying cause, shorten a disease’s duration, or do a combination of these things.The relevant symptoms will vary depending upon the intended indication of a particular API.

[0093] "Treating" and "treatment" as used herein include prophylactic treatment. Treatment methods include administering to a subject a therapeutically effective amount of a compound described herein. The administering step may consist of a single administration or may include a series of administrations. The length of the treatment period depends on a variety of factors, such as the severity of the condition, the age of the patient, the concentration of the compound, the activity of the compositions used in the treatment, or a combination thereof. It will also be appreciated that the effective dosage of an agent used for the treatment or prophylaxis may increase or decrease over the course of a particular treatment or prophylaxis regime. Changes in dosage may result and become apparent by standard diagnostic assays known in the art. In some instances, chronic administration may be required. For example, the compositions are administered to the subject in an amount and for a duration sufficient to treat the patient.

[0094] The term “prevent” refers to a decrease in the occurrence of disease symptoms in a patient. As indicated above, the prevention may be complete (no detectable symptoms) orAttorney Docket No.: 53160-716.601 partial, such that fewer symptoms are observed than would likely occur absent treatment. In certain embodiments, prevent refers to slowing the progression of the disease, disorder orcondition or inhibiting progression thereof to a harmful or otherwise undesired state.

[0095] “Patient” or “subject in need thereof” refers to a living organism suffering from orprone to a disease or condition that can be treated by administration of a pharmaceuticalcomposition as provided herein. Non-limiting examples include humans, other mammals, bovines, rats, mice, dogs, monkeys, goat, sheep, cows, deer, and other non-mammalian animals. In some embodiments, a patient is human.

[0096] A “effective amount” is an amount sufficient for a compound to accomplish a stated purpose relative to the absence of the compound (e.g., achieve the effect for which it is administered, treat a disease, reduce enzyme activity, increase enzyme activity, reduce a signaling pathway, or reduce one or more symptoms of a disease or condition). An example of an “effective amount” is an amount sufficient to contribute to the treatment, prevention, orreduction of a symptom or symptoms of a disease, which could also be referred to a s a“therapeutically effective amount.” A “reduction” of a symptom or symptoms (and grammatical equivalents of this phrase) means decreasing of the severity or frequency of the symptom(s), or elimination of the symptom(s). A “prophylactically effective amount” of a drug is an amount of a drug that, when administered to a subject, will have the intended prophylactic effect, e.g., preventing or delaying the onset (or reoccurrence) of an injury, disease, pathology or condition, or reducing the likelihood of the onset (or reoccurrence) of an injury, disease, pathology, or condition, or their symptoms. The full prophylactic effect does not necessarily occur by administration of one dose, and may occur only after administration of a series of doses. Thus, a prophylactically effective amount may be administered in one or more administrations. An “activity decreasing amount,” as used herein, refers to an amount of antagonist required todecrease the activity of an enzyme relative to the absence of the antagonist. A “ functiondisrupting amount,” as used herein, refers to the amount of antagonist required to disrupt the function of an enzyme or protein relative to the absence of the antagonist. The exact amounts will depend on the purpose of the treatment, and will be ascertainable by one skilled in the art using known techniques (see, e.g., Lieberman, Pharmaceutical Dosage Forms (vols.1-3, 1992);Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999); Pickar,Dosage Calculations (1999); and Remington: The Science and Practice of Pharmacy , 20thEdition, 2003, Gennaro, Ed., Lippincott, Williams & Wilkins). The therapeutically effective amount can be ascertained by measuring relevant physiological effects, and it can be adjusted in connection with the dosing regimen and diagnostic analysis of the subject’s condition, and theAttorney Docket No.: 53160-716.601 like. By way of example, measurement of the serum level of an inhibitor (or, e.g., a metabolite thereof) at a particular time post-administration may be indicative of whether a therapeutically effective amount has been administered.

[0097] For any compound described herein, the therapeutically effective amount can be initially determined from cell culture assays. Target concentrations will be those concentrations of active compound(s) that are capable of achieving the methods described herein, as measured using the methods described herein or known in the art.

[0098] As is well known in the art, therapeutically effective amounts for use in humans can also be determined from animal models. For example, a dose for humans can be formulated to achieve a concentration that has been found to be effective in animals. The dosage in humans can be adjusted by monitoring compounds effectiveness and adjusting the dosage upwards or downwards, as described above. Adjusting the dose to achieve maximal efficacy in humans based on the methods described above and other methods is well within the capabilities of the ordinarily skilled artisan. Adjusting the dose to achieve maximal therapeutic window efficacy or toxicity in humans based on the methods described above and other methods is well within the capabilities of the ordinarily skilled artisan.

[0099] The term “therapeutically effective amount,” as used herein, refers to that amount of the therapeutic agent sufficient to ameliorate the disorder, as described herein. For example, for the given parameter, a therapeutically effective amount will show an increase or decrease of at least 5%, 10%, 15%, 20%, 25%, 40%, 50%, 60%, 75%, 80%, 90%, or at least 100%. Therapeutic efficacy can also be expressed as “-fold” increase or decrease. For example, a therapeutically effective amount can have at least a 1.2-fold, 1.5-fold, 2-fold, 5-fold, or more effect over a control.

[0100] Dosages may be varied depending upon the requirements of the patient and the compound being employed. The dose administered to a patient, in the context of the present disclosure should be sufficient to effect a beneficial therapeutic response in the patient over time. The size of the dose also will be determined by the existence, nature, and extent of any adverse side-effects. Determination of the proper dosage for a particular situation is within the skill of the practitioner. Generally, treatment is initiated with smaller dosages which are less than the optimum dose of the compound. Thereafter, the dosage is increased by small increments until the optimum effect under circumstances is reached. Dosage amounts and intervals can be adjusted individually to provide levels of the administered compound effective for the particular clinical indication being treated. This will provide a therapeutic regimen that iscommensurate with the severity of the individual's disease state.Attorney Docket No.: 53160-716.601

[0101] As used herein, the term "administering" means subcutaneous (i.e., “SC,” “subQ,” or “SQ”) administration, oral administration, administration as a suppository, topical contact or administration, intravenous, parenteral, intraperitoneal, intramuscular, intraosseous, intralesional, intrathecal, intracranial, intranasal, epidural, or the implantation of a slow-release device, e.g., a mini-osmotic pump, to a subject. Administration is by any route, including parenteral and transmucosal (e.g., buccal, sublingual, palatal, gingival, nasal, vaginal, rectal, transvaginal, or transdermal). Parenteral administration includes, e.g., intravenous, intramuscular, intra-arteriole, intradermal, subcutaneous, intraperitoneal, intraventricular, and intracranial. Other modes of delivery include, but are not limited to, the use of liposomal formulations, intravenous infusion, transdermal patches, etc. By "co-administer" it is meant that a composition described herein is administered at the same time, just prior to, or just after the administration of one or more additional therapies (e.g., anti-cancer agent, chemotherapeutic, or treatment for a neurodegenerative disease). The compound of the disclosure can be administered alone or can be coadministered to the patient. Coadministration is meant to include simultaneous or sequential administration of the compound individually or in combination (more than one compound or agent). Thus, the preparations can also be combined, when desired, with other active substances (e.g., to reduce metabolic degradation). The compositions of the present disclosure can be delivered by transdermally, by a topical route, formulated as applicator sticks, solutions, suspensions, emulsions, gels, creams, ointments, pastes, jellies, paints, powders, and aerosols. Oral preparations include tablets, pills, powder, dragees, capsules, liquids, lozenges, cachets, gels, syrups, slurries, suspensions, etc., suitable for ingestion by the patient. Solid form preparations include powders, tablets, pills, capsules, cachets, suppositories, and dispersible granules. Liquid form preparations include solutions, suspensions, and emulsions, for example, water or water / propylene glycol solutions. The compositions of the present disclosure may additionally include components to provide sustained release and / or comfort. Such components include high molecular weight, anionic mucomimetic polymers, gelling polysaccharides and finely-divided drug carrier substrates. These components are discussed in greater detail in U.S. Pat. Nos.4,911,920; 5,403,841; 5,212,162; and 4,861,760. The entire contents of these patents are incorporated herein by reference in their entirety for all purposes. The compositions of the present disclosure can also be delivered as microspheres for slow release in the body. For example, microspheres can be administered via intradermal injection of drug-containing microspheres, which slowly release subcutaneously (see Rao, J. Biomater Sci. Polym. Ed.7:623- 645, 1995; as biodegradable and injectable gel formulations (see, e.g., Gao Pharm. Res.12:857- 863, 1995); or, as microspheres for oral administration (see, e.g., Eyles, J. Pharm. Pharmacol.Attorney Docket No.: 53160-716.601 49:669-674, 1997). In another embodiment, the formulations of the compositions of the present disclosure can be delivered by the use of liposomes which fuse with the cellular membrane or are endocytosed, e.g., by employing receptor ligands attached to the liposome, which bind to surface membrane protein receptors of the cell resulting in endocytosis. By using liposomes, particularly where the liposome surface carries receptor ligands specific for target cells, or are otherwise preferentially directed to a specific organ, one can focus the delivery of the compositions of the present disclosure into the target cells in vivo. (See, e.g., Al-Muhammed, J. Microencapsul.13:293-306, 1996; Chonn, Curr. Opin. Biotechnol.6:698-708, 1995; Ostro, Am. J. Hosp. Pharm.46:1576-1587, 1989). The compositions of the present disclosure can also be delivered as nanoparticles.

[0102] By “co-administer" it is meant that a composition described herein is administered at the same time, just prior to, or just after the administration of one or more additional therapies. The compounds of the disclosure can be administered alone or can be coadministered to the patient. Coadministration is meant to include simultaneous or sequential administration of the compounds individually or in combination (more than one compound). The compositions of the present disclosure can be delivered transdermally, by a topical route, or formulated as applicator sticks, solutions, suspensions, emulsions, gels, creams, ointments, pastes, jellies, paints, powders, and aerosols.

[0103] Utilizing the teachings provided herein an effective prophylactic or therapeutic treatment regimen can be planned that does not cause substantial toxicity and yet is effective to treat the clinical symptoms demonstrated by the particular patient. This planning should involve the careful choice of active compound by considering factors such as compound potency, relative bioavailability, patient body weight, presence and severity of adverse side effects, mode of administration and the toxicity profile of the selected agent.

[0104] The compounds described herein can be used in combination with one another, with other active agents known to be useful in treating a mental or psychiatric disorder, a mood disorder, a neurological condition or disorder, a metabolic disorder (e.g., type 2 diabetes mellitus and / or complications thereof), endometriosis, glaucoma, pain, Parkinson’s disease, migraine headache, viral infection, bacterial infection, fungal infection, autoimmune disease, lymphoma, pancreatitis, opioid overdose, flu infection, or an inflammatory disorder.

[0105] In some embodiments, co-administration includes administering one active agent within 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 20, 24 hours, 2 days, 4 days, 1 week or 1 month of a second active agent. Co-administration includes administering two active agents simultaneously, approximately simultaneously (e.g., within about 1, 5, 10, 15, 20, or 30 minutes of each other),Attorney Docket No.: 53160-716.601 or sequentially in any order. In some embodiments, co-administration can be accomplished by co-formulation, e.g., preparing a single pharmaceutical composition including both active agents. In other embodiments, the active agents can be formulated separately. In another embodiment, the active and / or adjunctive agents may be linked or conjugated to one another. In some embodiments, the compounds described herein may be combined with treatments for infections (e.g., bacterial infections), inflammation, and / or vasodilation.

[0106] The compounds described herein can be administered to treat a metabolic disease or disorder (e.g., type 2 diabetes mellitus and / or complications thereof), a mental or psychiatric disorder, a mood disorder, a neurological condition or disorder, endometriosis, glaucoma, pain, Parkinson’s disease, migraine headache, viral infection, bacterial infection, fungal infection, autoimmune disease, lymphoma, pancreatitis, opioid overdose, flu infection, or an inflammatory disorder. In this regard, the compounds disclosed herein may be administered either alone to treat such diseases or disorders or may be co-administered with another therapeutic agent to treat such diseases or disorders.

[0107] The compounds disclosed herein may be co-administered with other active agents including but not limited to antidepressants, antipsychotics, anti-inflammatories, anxiolytics, and / or analgesics.

[0108] The APIs (e.g., rotigotine, eletriptan, copanlisib, remdesivir, nafamostat (nafamostat mesylate), melevodopa, tigecycline, naloxone, amikacin, 1-amantadine, 2-amantadine, rimantadine, midazolam, amifampridine, caspofungin, rapamycin, clonidine, ketamine, methoxetamine, deschloroketamine, tryptamines, phenethylamines, lysergamide compounds, opioids, cathinone compounds, 3,4-methylenedioxyamphetamine compound derivatives, aminoalkyl-substituted benzofurans, substituted amphetamines, aminoindanes, stimulants, diphenhydramine, hydroxazine, phenylephrine, dopamine, adrenaline, lidocaine, oxymetazoline, clemastine, chlorpheniramine, or 6-chloro-2-aminotetralin, etc.) disclosed herein may be administered once daily until study reached endpoint. The inhibitors disclosed herein may be administered at least three times but in some studies four or more times depending on the length of the study and / or the design of the study.

[0109] The term “bioavailability (F),” as used herein, refers to the fraction of a dose of drug (e.g., epinephrine) that is absorbed from its site of administration and reaches, in an unchanged form, the systemic circulation. The term “absolute bioavailability” is used when the fraction of absorbed drug is related to its I.V. bioavailability. It may be calculated using the following formula:Attorney Docket No.: 53160-716.601

[0110]

[0111] The term relative bioavailability (Frel) is used to compare two different extravascular routes of drug administration and it may be calculated using the following formula:

[0112]

[0113] The term “clearance (CL),” as used herein, refers to the rate at which a drug is eliminated divided by its plasma concentration, giving a volume of plasma from which drug is completely removed per unit of time. CL is equal to the elimination rate constant (λ) multiplied by the volume of distribution (Vd), wherein “Vd” is the fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma. The term “apparent clearance (CL / F),” as used herein, refers to clearance that does not take into account the bioavailability of the drug. It is the ratio of the dose over the AUC.

[0114] “Control” or “control experiment” is used in accordance with its plain ordinary meaning and refers to an experiment in which the subjects or reagents of the experiment are treated as in a parallel experiment except for omission of a procedure, reagent, or variable of the experiment. In some instances, the control is used as a standard of comparison in evaluating experimental effects. In some embodiments, a control is the measurement of the activity of a protein in the absence of a compound as described herein (including embodiments and examples).

[0115] Generally, dosage levels of pharmaceutical compounds (API) in the compositions can range from about 5 μg / kg to about 10 mg / kg, from about 0.5 mg / kg to about 5 mg / kg, from about 1 mg / kg to about 3 mg / kg, or a fixed dose from about 10-100 mg, or 20-75mg, or 3-60 mg, or 10-250 mg, or 10-400 mg, or an amount greater than 400 mg.

[0116] “Substantially pure” indicates that a component makes up greater than about 50% of the total content of the composition, and typically greater than about 60% of the total content. More typically, “substantially pure” refers to compositions in which at least 75%, at least 85%, at least 90% or more of the total composition is the component of interest. In some cases, the polypeptide will make up greater than about 90%, or greater than about 95% of the total content of the composition (percentage in a weight per weight basis).

[0117] It should be noted that throughout the application that alternatives are written in Markush groups, for example, each amino acid position that contains more than one possibleAttorney Docket No.: 53160-716.601 amino acid. It is specifically contemplated that each member of the Markush group should be considered separately, thereby comprising another embodiment, and the Markush group is not to be read as a single unit.

[0118] “Contacting” is used in accordance with its plain ordinary meaning and refers to the process of allowing at least two distinct species (e.g., chemical compounds including biomolecules or cells) to become sufficiently proximal to react, interact or physically touch. It should be appreciated; however, the resulting reaction product can be produced directly from a reaction between the added reagents or from an intermediate from one or more of the added reagents that can be produced in the reaction mixture.

[0119] The term “contacting” may include allowing two species to react, interact, or physically touch, wherein the two species may be a compound as described herein and a protein or enzyme. In some embodiments contacting includes allowing a compound described herein to interact with a protein or enzyme that is involved in a signaling pathway (e.g., MAP kinase pathway).

[0120] As defined herein, the terms “activation,” “activate,” “activating,” and the like in reference to a protein refers to conversion of a protein into a biologically active derivative from an initial inactive or deactivated state. The terms reference activation, or activating, sensitizing, or up-regulating signal transduction or enzymatic activity or the amount of a protein decreased in a disease.

[0121] The terms “agonist,” “activator,” “upregulator,” etc., refer to a substance capable ofdetectably increasing the expression or activity of a given gene or protein . The agonist canincrease expression or activity 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or more in comparison to a control in the absence of the agonist. In certain instances, expression or activity is 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold or higher than the expression or activity in the absence of the agonist. In embodiments, an agonist is a molecule that interacts with a target to cause or promote an increase in the activation of the target. In embodiments, activators are molecules that increase, activate, facilitate, enhance activation, sensitize, or up-regulate, e.g., a gene, protein, ligand, receptor, or cell.

[0122] The “activity” of a molecule may describe or refer to the binding of the molecule to a ligand or to a receptor; to catalytic activity; to the ability to stimulate gene expression or cell signaling, differentiation, or maturation; to antigenic activity; to the modulation of activities of other molecules; and the like.

[0123] The term “osmolality” as described herein is defined as the number of osmoles (Osm) of solute per kilogram of solvent (osmol / kg or Osm / kg).Attorney Docket No.: 53160-716.601

[0124] The term “osmolarity” as described herein is defined is defined as the number of osmoles of solute per liter (L) of solution (osmol / L or Osm / L).

[0125] Osmolarity may be calculated from osmolality as follows: osmolarity = osmolality x (ρsol-ca); where ρsolis the density of the solution in g / mL and cais the (anhydrous) solute concentration in g / mL. Unless expressly stated otherwise, osmolarity is calculated using osmolality according to the preceding formula. Alternatively, osmolarity may be calculated experimentally.

[0126] Compositions

[0127] Complexing Agent Salts of Pharmaceutical Compounds

[0128] Provided herein are salts of conjugate acid forms of pharmaceutical compounds comprising at least one basic nitrogen and conjugate base forms of complexing agents. Such salts have advantages over other salts of compounds because they are more soluble than many other salt forms owing to the nature of the complexing agent and its ability to solubilize compounds. Additionally, in some embodiments, the preparation of such complexing agent / pharmaceutical compound salts results in a composition that will have a lower osmolality upon dissolution or otherwise in solution than a combination of individual salts of each component, or of each component individually.

[0129] In an aspect, provided herein is a pharmaceutically acceptable salt of a compound pharmaceutical comprising: (i) a pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate orhydrate thereof, wherein the pharmaceutical compound comprises a protonated nitrogen atomand has a pKa of at least 1; and (ii) a conjugate base of a complexing agent comprising a plurality of acidic functional groups, wherein at least one acidic functional group of the plurality of acidic functional groups acts as a counterion of the pharmaceutical compound, wherein the pharmaceutically acceptable salt has a ratio of the conjugate base of the complexing agent to the pharmaceutical compound that is from about 1:1 to about 1:4. In some embodiments, the pharmaceutical compound has a pKa of about 1 to about 7. In some embodiments, the pharmaceutical compound has a pKa of about 1 to about 5. In some embodiments, the pharmaceutical compound has a pKa of about 5 to about 7. In some embodiments, the conjugate base interacts with a monovalent cation. In some embodiments, the monovalent cation comprises Na+, K+, H+, Li+, or a combination or two or more thereof. In some embodiments, the pharmaceutical compound is an antiviral compound, an antibacterial compound, an anti-fungal compound, a compound for treatment of a neurological disorder, a compound for treatment of Parkinson’s disease, a treatment for migraine headache, a treatment for autoimmune disease, aAttorney Docket No.: 53160-716.601 treatment for cancer, a treatment for lymphoma, a treatment for pancreatitis, a treatment for opioid overdose, a treatment for flu infection, or a treatment for an inflammatory disorder. In some embodiments, the pharmaceutical compound comprises rotigotine, eletriptan, DXM, copanlisib, remdesivir, nafamostat (nafamostat mesylate), melevodopa, tigecycline, naloxone, amikacin, 1-amantadine, 2-amantadine, rimantadine, amifampridine, rapamycin, clonidine, or caspofungin. In some embodiments, the pharmaceutical compound has a solubility below a threshold value. In some embodiments, the pharmaceutical compound has a solubility above a threshold value. In some embodiments, the pharmaceutical compound comprises a pKa above a threshold value. In some embodiments, the pharmaceutical compound comprises a pKa below a threshold value.

[0130] In some embodiments, the pharmaceutical compound has a solubility of more than 100 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 90 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 80 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 70 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 60 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 50 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 45 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 40 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 35 mg / ml as salt. Insome embodiments, the pharmaceutical compound has a solubility of more than 30 mg / ml assalt. In some embodiments, the pharmaceutical compound has a solubility of more than 25 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 20 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 10 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 9 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 8 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 7 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 6 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 5 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 4 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 3 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more 2 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 1 mg / ml as salt.Attorney Docket No.: 53160-716.601 In some embodiments, the pharmaceutical compound has a solubility of more than 0.9 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.8 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.7 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.6 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.5 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.4 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.3 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.2 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.1 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.09 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.08mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility o f morethan 0.07 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.06 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.05 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.04 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.03 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.02 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.01 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.009 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.008 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.007 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.006 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.005 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.004 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.003 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.002 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.001 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.9 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.8 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.7 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility ofAttorney Docket No.: 53160-716.601 more than 0.6 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.5 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.4 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.3 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.2 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.1 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.09 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.08 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.07 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.06 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.05 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.04 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.03 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.02 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.01 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.009 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.008 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.007 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.006 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.005 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.004 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.003 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.002 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.001 µg / ml as salt. In some embodiments, the solubility of the pharmaceutical compound as salt is measured in an aqueous medium. In some embodiments, the solubility of the pharmaceutical compound as salt is measured in an organic solvent. In some embodiments, the aqueous medium comprises water. Insome embodiments, the salt of the pharmaceutical compound comprises a HCl salt.

[0131] In some embodiments, the pharmaceutical compound has a solubility of between about 0.001 mg / ml and 100 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of between about 0.01 mg / ml and 50 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of between about 0.02 mg / ml and 40 mg / ml as salt. InAttorney Docket No.: 53160-716.601 some embodiments, the pharmaceutical compound has a solubility of between about 0.03 mg / ml and 30 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of between about 0.04 mg / ml and 20 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of between about 0.05 mg / ml and 10 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of between about 0.06 mg / ml and 5 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of between about 0.07 mg / ml and 4 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of between about 0.09 mg / ml and 3 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of between about 0.1 mg / ml and 2 mg / ml as salt. In some embodiments, the solubility of the pharmaceutical compound as salt is measured in an aqueous medium. In some embodiments, the solubility of the pharmaceutical compound as salt is measured in an organic solvent. In some embodiments, the aqueous medium comprises water.In some embodiments, the salt of the pharmaceutical compound comprises a HCl salt.

[0132] In some embodiments, the pharmaceutical compound has a solubility of less than 100 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 90 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 80 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 70 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 60 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 50 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 45 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 40 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 35 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 30 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 25 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 20 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 10 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 9 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 8 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 7 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 6 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 5 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 4 mg / ml as salt. In some embodiments, the pharmaceutical compound has aAttorney Docket No.: 53160-716.601 solubility of less than 3 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more 2 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 1 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.9 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.8 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.7 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.6 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.5 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.4 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.3 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.2 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.1 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.09 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.08 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.07 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.06 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.05 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.04 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.03 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.02 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.01 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.009 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.008 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.007 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.006 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.005 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.004 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.003 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.002 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.001 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.9 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.8 µg / ml asAttorney Docket No.: 53160-716.601 salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.7 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.6 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.5 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.4 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.3 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.2 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.1 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.09 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.08 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.07 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.06 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.05 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.04 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.03 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.02 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.01 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.009 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.008 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.007 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.006 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.005 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.004 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.003 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.002 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.001 µg / ml as salt. In some embodiments, the solubility of the pharmaceutical compound as salt is measured in an aqueous medium. In some embodiments, the solubility of the pharmaceutical compound as salt is measured in an organic solvent. In some embodiments, the aqueous medium comprises water. In some embodiments, the salt of the pharmaceutical compound comprises a HCl salt.

[0133] In some embodiments, the pharmaceutical compound has a solubility of more than 100 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility ofAttorney Docket No.: 53160-716.601 more than 90 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 80 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 70 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 60 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 50 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 45 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 40 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 35 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 30 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 25 mg / ml as freebase. In some embodiments, thepharmaceutical compound has a solubility of more than 20 mg / ml as f reebase. In someembodiments, the pharmaceutical compound has a solubility of more than 10 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 9 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 8 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 7 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 6 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 5 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 4 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 3 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more 2 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 1 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.9 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.8 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.7 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.6 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.5 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.4 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.3 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.2 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.1 mg / ml as freebase. In some embodiments, theAttorney Docket No.: 53160-716.601 pharmaceutical compound has a solubility of more than 0.09 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.08 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.07 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.06 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.05 mg / ml as freebase. In some embodiments, the pharmaceuticalcompound has a solubility of more than 0.04 mg / ml as freebase. In some embodiments , thepharmaceutical compound has a solubility of more than 0.03 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.02 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.01 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.009 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.008 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.007 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.006 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.005 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.004 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.003 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.002 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.001 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.9 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.8 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.7 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.6 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.5 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.4 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.3 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.2 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.1 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.09 µg / ml asfreebase. In some embodiments, the pharmaceutical compound has a so lubility of more than0.08 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility ofAttorney Docket No.: 53160-716.601 more than 0.07 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.06 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.05 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.04 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.03 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.02 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.01 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.009 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.008 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.007 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.006 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.005 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.004 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.003 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.002 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.001 µg / ml as freebase. In some embodiments, the solubility of the pharmaceutical compound as freebase is measured in an aqueous medium. In some embodiments, the solubility of the pharmaceutical compound as freebase is measured in an organic solvent. In some embodiments, the aqueous medium comprises water.

[0134] In some embodiments, the pharmaceutical compound has a solubility of between about 0.001 mg / ml and 100 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of between about 0.01 mg / ml and 50 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of between about 0.02 mg / ml and 40 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of between about 0.03 mg / ml and 30 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of between about 0.04 mg / ml and 20 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of between about 0.05 mg / ml and 10 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of between about 0.06 mg / ml and 5 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of between about 0.07 mg / ml and 4 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of between about 0.09 mg / ml and 3 mg / ml asAttorney Docket No.: 53160-716.601 freebase. In some embodiments, the pharmaceutical compound has a solubility of between about 0.1 mg / ml and 2 mg / ml as freebase. In some embodiments, the solubility of the pharmaceuticalcompound as freebase is measured in an aqueous medium. In some embodiments, the solub ilityof the pharmaceutical compound as freebase is measured in an organic solvent. In some embodiments, the aqueous medium comprises water.

[0135] In some embodiments, the pharmaceutical compound has a solubility of less than 100 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 90 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 80 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 70 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 60 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 50 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 45 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 40 mg / ml asfreebase. In some embodiments, the pharmaceutical compound has a solubility of less than 35mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 30 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 25 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 20 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 10 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 9 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 8 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 7 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 6 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 5 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 4 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 3 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more 2 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 1 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.9 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.8 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.7 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.6Attorney Docket No.: 53160-716.601 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.5 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.4 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.3 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.2 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.1 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.09 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.08 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.07 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.06 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.05 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.04 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.03 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.02 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.01 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.009 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.008 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.007 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.006 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.005 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.004 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.003 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.002 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.001 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.9 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.8 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.7 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.6 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.5 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.4 µg / ml as freebase. In some embodiments, the pharmaceuticalAttorney Docket No.: 53160-716.601 compound has a solubility of less than 0.3 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.2 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.1 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.09 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.08 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.07 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.06 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.05 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.04 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.03 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.02 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.01 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.009 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.008 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.007 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.006 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.005 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.004 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.003 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.002 µg / ml as freebase. In some embodiments, the pharmaceuticalcompound has a solubility of less than 0.001 µg / ml as freebase. In some embodiments, th esolubility of the pharmaceutical compound as freebase is measured in an aqueous medium. In some embodiments, the solubility of the pharmaceutical compound as freebase is measured in an organic solvent. In some embodiments, the aqueous medium comprises water.

[0136] In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:1 to about 1:4. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:1.1 to about 1:3.9. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:1.2 to about 1:3.8. In some embodiments, the ratio of the conjugate base of the complexing agent to theAttorney Docket No.: 53160-716.601 pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:1.3 to about 1:3.7. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:1.4 to about 1:3.6. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:1.5 to about 1:3.5. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:1.6 to about 1:3.4. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:1.7 to about 1:3.3. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:1.8 to about 1:3.2. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:1.9 to about 1:3.1. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:2 to about 1:3. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:2.1 to about 1:2.9. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:2.2 to about1:2.8. In some embodiments, the ratio of the conjugate base of the complex ing agent to thepharmaceutical compound in the pharmaceutically acceptable salt is from about 1:2.3 to about 1:2.7. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:2.4 to about 1:2.6. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:1 to about 1:4, about 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2.0, 1:2.1, 1:2.2, 1:2.3, 1:2.4, 1:2.5, 1:2.6, 1:2.7, 1:2.8, 1:2.9, 1:3.0, 1:3.1, 1:3.2, 1:3.3, 1:3.4, 1:3.5, 1:3.6, 1:3.7, 1:3.8, 1:3.9, or about 1:4.0, or any ratio therebetween.

[0137] In some embodiments, the complexing agent acts as the counterion to between 1 to 4 molecules of the pharmaceutical compound in the pharmaceutically acceptable salt. In some embodiments, the complexing agent further comprises a non-polar region. In some embodiments, the pharmaceutically acceptable salt comprises an additional molar equivalent of the pharmaceutical compound in an unionized form compared to the amount of complexingAttorney Docket No.: 53160-716.601 agent. In some embodiments, the additional molar equivalent of the pharmaceutical compound in the unionized form is complexed to the complexing agent through the non-polar region.

[0138] In some embodiments, the solubility of the pharmaceutical compound in the pharmaceutically acceptable salt is higher than (i) the solubility of the pharmaceutical compound as a salt; or (ii) the solubility of the pharmaceutical compound in a salt comprising the pharmaceutical compound in freebase form that is complexing to a non-polar pore of the complexing agent, wherein the pharmaceutical compound has the same concentration in the pharmaceutically acceptable salt, the pharmaceutical compound as a salt, and the salt comprising the pharmaceutical compound in freebase form. In some embodiments, the solubility of the pharmaceutical compound in the pharmaceutically acceptable salt is higher than the solubility of the pharmaceutical compound in a salt comprising the pharmaceutical compound and complexing agent with a higher molar ratio of the pharmaceutical compound to the complexing agent, wherein the pharmaceutical compound has the same concentration in the pharmaceutically acceptable salt and the salt with a higher molar ratio of the pharmaceutical compound to the complexing agent. In some embodiments, the solubility of the pharmaceutical compound in the pharmaceutically acceptable salt has an increase of at least 2-fold, 3-fold, 4- fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 15-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, or 100-fold compared with (i) the solubility of the pharmaceutical compound as a salt; or (ii) the solubility of the pharmaceutical compound in a salt comprising the pharmaceutical compound in freebase form that is complexing to a non-polar pore of the complexing agent, wherein the pharmaceutical compound has the same concentration in the pharmaceutically acceptable salt, the pharmaceutical compound as a salt, and the salt comprising the pharmaceutical compound in freebase form. In some embodiments, the solubility of the pharmaceutical compound in the pharmaceutically acceptable salt has an increase of at least 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 15-fold, 20-fold, 30- fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, or 100-fold compared with the solubility of the pharmaceutical compound in a salt comprising the pharmaceutical compound and complexing agent with a higher molar ratio of the pharmaceutical compound to the complexing agent, wherein the pharmaceutical compound has the same concentration in the pharmaceutically acceptable salt and the salt with a higher molar ratio of the pharmaceutical compound to the complexing agent.

[0139] In an aspect, provided herein is a pharmaceutically acceptable salt of a compound pharmaceutical comprising: (i) a pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate orAttorney Docket No.: 53160-716.601hydrate thereof, wherein the pharmaceutical compound comprises a protonated nitrogen atomand has a pKa of at least 1; (ii) a conjugate base of a complexing agent comprising a plurality of acidic functional groups, wherein the plurality of acidic functional groups comprise a conjugate base of an acid which acts as a counterion for the protonated nitrogen atom of the pharmaceutical compound, wherein the pharmaceutically acceptable salt has a ratio of the conjugate base of the complexing agent to the pharmaceutical compound that is from about 1:1 to about 1:4; and an additional molar equivalent of the pharmaceutical compound, wherein the additional molar equivalent of the pharmaceutical compound is unionized. In some embodiments, the pharmaceutical compound has a pKa of about 1 to about 7, about 1 to about 6, about 1 to about 5, about 1 to about 4, about 1 to about 3, about 1 to about 2. In some embodiments, the pharmaceutical compound has a pKa of about 1 to about 5. In some embodiments, the pharmaceutical compound has a pKa of about 4 to about 7. In some embodiments, the complexing agent acts as the counterion to between 1 to 4 molecules of the pharmaceutical compound in the pharmaceutically acceptable salt. In some embodiments, the pharmaceutical compound comprises a solubility below a threshold value. In some embodiments, the pharmaceutical compound comprises a solubility above a threshold value. In some embodiments, the pharmaceutical compound comprises a pKa above a threshold value. In some embodiments, the pharmaceutical compound comprises a pKa below a threshold value.

[0140] In some embodiments, the complexing agent further comprises a non-polar region. In some embodiments, the additional molar equivalent of the pharmaceutical compound in the unionized form is complexed to the complexing agent through the non-polar region. In some embodiments, the pharmaceutical compound is an antiviral compound, an antibacterial compound, an anti-fungal compound, a compound for treatment of a neurological disorder, a compound for treatment of Parkinson’s disease, a treatment for migraine headache, a treatment for autoimmune disease, a treatment for cancer, a treatment for lymphoma, a treatment for pancreatitis, a treatment for opioid overdose, a treatment for flu infection, or a treatment for an inflammatory disorder. In some embodiments, the pharmaceutical compound comprises rotigotine, eletriptan, copanlisib, remdesivir, nafamostat (nafamostat mesylate), melevodopa, tigecycline, naloxone, amikacin, 1-amantadine, 2-amantadine, rimantadine, amifampridine, rapamycin, clonidine, or caspofungin. In some embodiments, the complexing agent is sulfobutylether-β-cyclodextrin.

[0141] In some embodiments, the pharmaceutical compound has a solubility of more than 100 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 90 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility ofAttorney Docket No.: 53160-716.601 more than 80 mg / ml as salt. In some embodiments, the pharmaceutical compound has asolubility of more than 70 mg / ml as salt. In some embodiments, the pharmaceutical compoundhas a solubility of more than 60 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 50 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 45 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 40 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 35 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 30 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 25 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 20 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 10 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 9 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 8 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 7 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 6 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 5 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 4 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 3 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more 2 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 1 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.9 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.8 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.7 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.6 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.5 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.4 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.3 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.2 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.1 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.09 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.08 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of moreAttorney Docket No.: 53160-716.601 than 0.07 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.06 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.05 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.04 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.03 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.02 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.01 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.009 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.008 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.007 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.006 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.005 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.004 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.003 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.002 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.001 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.9 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.8 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.7 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.6 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.5 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.4 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.3 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.2 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.1 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.09 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.08 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.07 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.06 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.05 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.04 µg / ml as salt. In some embodiments, the pharmaceutical compound has aAttorney Docket No.: 53160-716.601 solubility of more than 0.03 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.02 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.01 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.009 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.008 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.007 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.006 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.005 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.004 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.003 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.002 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more than 0.001 µg / ml as salt. In some embodiments, the solubility of the pharmaceutical compound as salt is measured in an aqueous medium. In some embodiments, the solubility of the pharmaceutical compound as salt is measured in an organic solvent. In some embodiments, the aqueous medium comprises water. Insome embodiments, the salt of the pharmaceutical compound comprises a HCl salt.

[0142] In some embodiments, the pharmaceutical compound has a solubility of between about 0.001 mg / ml and 100 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of between about 0.01 mg / ml and 50 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of between about 0.02 mg / ml and 40 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of between about 0.03 mg / ml and 30 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of between about 0.04 mg / ml and 20 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of between about 0.05 mg / ml and 10 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of between about 0.06 mg / ml and 5 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of between about 0.07 mg / ml and 4 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of between about 0.09 mg / ml and 3 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of between about 0.1 mg / ml and 2 mg / ml as salt. In some embodiments, the solubility of the pharmaceutical compound as salt is measured in an aqueous medium. In some embodiments, the solubility of the pharmaceutical compound as salt is measured in an organic solvent. In some embodiments, the aqueous medium comprises water.In some embodiments, the salt of the pharmaceutical compound comprises a HCl salt.Attorney Docket No.: 53160-716.601

[0143] In some embodiments, the pharmaceutical compound has a solubility of less than 100 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 90 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 80 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 70 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 60 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 50 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 45 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 40 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 35 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 30 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 25 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 20 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 10 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 9 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 8 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 7 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 6 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 5 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 4 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 3 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of more 2 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 1 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.9 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.8 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.7 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.6 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.5 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.4 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.3 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.2 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.1 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.09Attorney Docket No.: 53160-716.601 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.08 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.07 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.06 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.05 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.04 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.03 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.02 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.01 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.009 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.008 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.007 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.006 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.005 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.004 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.003 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.002 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.001 mg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.9 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.8 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.7 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.6 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.5 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.4 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.3 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.2 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.1 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.09 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.08 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.07 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.06 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.05 µg / ml as salt. InAttorney Docket No.: 53160-716.601 some embodiments, the pharmaceutical compound has a solubility of less than 0.04 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.03 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.02 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.01 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.009 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.008 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.007 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.006 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.005 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.004 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.003 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.002 µg / ml as salt. In some embodiments, the pharmaceutical compound has a solubility of less than 0.001 µg / ml as salt. In some embodiments, the solubility of the pharmaceutical compound as salt is measured in an aqueous medium. In some embodiments, the solubility of the pharmaceutical compound as salt is measured in an organic solvent. In some embodiments, the aqueous medium comprises water. In some embodiments, the salt of the pharmaceutical compound comprises a HCl salt.

[0144] In some embodiments, the pharmaceutical compound has a solubility of more than 100 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 90 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 80 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 70 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 60 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 50 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 45 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 40 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 35 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 30 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 25 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 20 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 10 mg / ml as freebase.Attorney Docket No.: 53160-716.601 In some embodiments, the pharmaceutical compound has a solubility of more than 9 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 8 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 7 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 6 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 5 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 4 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 3 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more 2 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 1 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.9 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.8 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.7 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.6 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.5 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.4 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.3 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.2 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.1 mg / ml as freebase. In some embodiments, thepharmaceutical compound has a solubility of more than 0.09 mg / ml as freebase. In someembodiments, the pharmaceutical compound has a solubility of more than 0.08 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.07 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.06 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.05 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.04 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.03 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.02 mg / ml asfreebase. In some embodiments, the pharmaceutical compound has a solubility of more than0.01 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.009 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.008 mg / ml as freebase. In some embodiments, the pharmaceuticalAttorney Docket No.: 53160-716.601 compound has a solubility of more than 0.007 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.006 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.005 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.004 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.003 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.002 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.001 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.9 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.8 µg / ml as freebase.In some embodiments, the pharmaceutical compound has a solubility of more than 0.7 µg / ml asfreebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.6 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.5 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.4 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.3 µg / ml as freebase. In some embodiments, the pharmaceuticalcompound has a solubility of more than 0.2 µg / ml as f reebase. In some embodiments, thepharmaceutical compound has a solubility of more than 0.1 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.09 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.08 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.07 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.06 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.05 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.04 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.03 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.02 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.01 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.009 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.008 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.007 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.006 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more thanAttorney Docket No.: 53160-716.601 0.005 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.004 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.003 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.002 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of more than 0.001 µg / ml as freebase. In some embodiments, the solubility of the pharmaceutical compound as freebase is measured in an aqueous medium. In some embodiments, the solubility of the pharmaceutical compound as freebase is measured in an organic solvent. In some embodiments, the aqueous medium comprises water.

[0145] In some embodiments, the pharmaceutical compound has a solubility of between about 0.001 mg / ml and 100 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of between about 0.01 mg / ml and 50 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of between about 0.02 mg / ml and 40 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of between about 0.03 mg / ml and 30 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of between about 0.04 mg / ml and 20 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of between about 0.05 mg / ml and 10 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of between about 0.06 mg / ml and 5 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of between about 0.07 mg / ml and 4 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of between about 0.09 mg / ml and 3 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of between about 0.1 mg / ml and 2 mg / ml as freebase. In some embodiments, the solubility of the pharmaceutical compound as freebase is measured in an aqueous medium. In some embodiments, the solubility of the pharmaceutical compound as freebase is measured in an organic solvent. In some embodiments, the aqueous medium comprises water.

[0146] In some embodiments, the pharmaceutical compound has a solubility of less than 100 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 90 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 80 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 70 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 60 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 50 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 45 mg / ml as freebase.Attorney Docket No.: 53160-716.601 In some embodiments, the pharmaceutical compound has a solubility of less than 40 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 35 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 30 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 25 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 20 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 10 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 9 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 8 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 7 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 6 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 5 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 4 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 3 mg / ml as freebase. In some embodiments, the pharmaceutical compoundhas a solubility of more 2 mg / ml as freebase. In some embodiments, the pharmaceutica lcompound has a solubility of less than 1 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.9 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.8 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.7 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.6 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.5 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.4 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.3 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.2 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.1 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.09 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.08 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.07 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.06 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.05 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.04 mg / ml as freebase. In someAttorney Docket No.: 53160-716.601 embodiments, the pharmaceutical compound has a solubility of less than 0.03 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.02 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.01 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.009 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.008 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.007 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.006 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.005 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.004 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.003 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.002 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.001 mg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.9 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.8 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.7 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.6 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.5 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.4 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.3 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.2 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.1 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.09 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.08 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.07 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.06 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.05 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.04 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.03 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.02 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.01Attorney Docket No.: 53160-716.601 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.009 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.008 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.007 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.006 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.005 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.004 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.003 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.002 µg / ml as freebase. In some embodiments, the pharmaceutical compound has a solubility of less than 0.001 µg / ml as freebase. In some embodiments, the solubility of the pharmaceutical compound as freebase is measured in an aqueous medium. In some embodiments, the solubility of the pharmaceutical compound as freebase is measured in an organic solvent. In some embodiments, the aqueous medium comprises water.

[0147] In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:1 to about 1:4.In some embodiments, the ratio of the conjugate base of the complexing agent to thepharmaceutical compound in the pharmaceutically acceptable salt is from about 1:1.1 to about 1:3.9. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:1.2 to about 1:3.8. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:1.3 to about 1:3.7. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:1.4 to about 1:3.6. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:1.5 to about 1:3.5. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:1.6 to about 1:3.4. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:1.7 to about 1:3.3. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:1.8 to about 1:3.2. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:1.9 to aboutAttorney Docket No.: 53160-716.601 1:3.1. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:2 to about 1:3. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:2.1 to about1:2.9. In some embodiments, the ratio of the conjugate base of the complexing agent to thepharmaceutical compound in the pharmaceutically acceptable salt is from about 1:2.2 to about 1:2.8. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:2.3 to about 1:2.7. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:2.4 to about 1:2.6. In some embodiments, the ratio of the conjugate base of the complexing agent to the pharmaceutical compound in the pharmaceutically acceptable salt is from about 1:1 to about 1:4, about 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2.0, 1:2.1, 1:2.2, 1:2.3, 1:2.4, 1:2.5, 1:2.6, 1:2.7, 1:2.8, 1:2.9, 1:3.0, 1:3.1, 1:3.2, 1:3.3, 1:3.4, 1:3.5, 1:3.6, 1:3.7, 1:3.8, 1:3.9, or about 1:4.0, or any ratio therebetween.

[0148] In some embodiments, the solubility of the pharmaceutical compound in the pharmaceutically acceptable salt is higher than (i) the solubility of the pharmaceutical compound as a salt; or (ii) the solubility of the pharmaceutical compound in a salt comprising the pharmaceutical compound in freebase form that is complexing to a non-polar pore of the complexing agent, wherein the pharmaceutical compound has the same concentration in the pharmaceutically acceptable salt, the pharmaceutical compound as a salt, and the salt comprising the pharmaceutical compound in freebase form. In some embodiments, the solubility of the pharmaceutical compound in the pharmaceutically acceptable salt is higher than the solubility of the pharmaceutical compound in a salt comprising the pharmaceutical compound and complexing agent with a higher molar ratio of the pharmaceutical compound to the complexing agent, wherein the pharmaceutical compound has the same concentration in the pharmaceutically acceptable salt and the salt with a higher molar ratio of the pharmaceutical compound to the complexing agent. In some embodiments, the solubility of the pharmaceuticalcompound in the pharmaceutically acceptable salt has an increase of at least 2 -fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 15-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, or 100-fold compared with (i) the solubility of the pharmaceutical compound as a salt; or (ii) the solubility of the pharmaceutical compound in a salt comprising the pharmaceutical compound in freebase form that is complexing to a non-polar pore of the complexing agent, wherein the pharmaceutical compound has the same concentrationAttorney Docket No.: 53160-716.601 in the pharmaceutically acceptable salt, the pharmaceutical compound as a salt, and the salt comprising the pharmaceutical compound in freebase form. In some embodiments, the solubility of the pharmaceutical compound in the pharmaceutically acceptable salt has an increase of at least 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 15-fold, 20-fold, 30- fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, or 100-fold compared with the solubility of the pharmaceutical compound in a salt comprising the pharmaceutical compound and complexing agent with a higher molar ratio of the pharmaceutical compound to the complexing agent, wherein the pharmaceutical compound has the same concentration in the pharmaceutically acceptable salt and the salt with a higher molar ratio of the pharmaceutical compound to the complexing agent.

[0149] In an aspect, provided herein is a pharmaceutically acceptable salt of a compound pharmaceutical comprising: (i) a pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the pharmaceutical compound comprises a prodrug comprising an unionized substance conjugated to a chemical entity, wherein the chemical entity comprises a protonated nitrogen atom and a pKa of about 1 to about 7; and (ii) a conjugate base of a complexing agent comprising a plurality of acidic functional groups, wherein the plurality of acidic functional groups comprise a conjugate base of an acid which acts as a counterion for the protonated nitrogen atom of the pharmaceutical compound. In some embodiments, the unionized substance comprises brexanolone. In some embodiments, the chemical entity comprises γ- aminobutyric acid (GABA). In some embodiments, the unionized substance comprises a steroid. In some embodiments, the steroid comprises hydrocortisone. In some embodiments, the pharmaceutically acceptable salt further comprises an additional molar equivalent of the unionized substance compared to the amount of complexing agent. In some embodiments, the complexing agent acts as the counterion to between 1 to 8 molecules of the pharmaceutical compound in the pharmaceutically acceptable salt. In some embodiments, the complexing agent further comprises a non-polar region. In some embodiments, the about 1 molar equivalent of the unionized substance is complexed to the complexing agent through the non-polar region. Insome embodiments, the complexing agent comprises a substituted cyclodextrin. In someembodiments, the complexing agent comprises a cyclodextrin substituted with at least one acidic functional group. In some embodiments, the cyclodextrin is substituted with 3 to 8 acidic functional groups. In some embodiments, the cyclodextrin is sulfobutylether-β-cyclodextrin. In some embodiments, the pharmaceutically acceptable salt has a ratio of the conjugate base of thecomplexing agent to the pharmaceutical compound that is from about 1:4 to about 1:10. In someAttorney Docket No.: 53160-716.601 embodiments, the pharmaceutically acceptable salt has a ratio of the conjugate base of thecomplexing agent to the pharmaceutical compound that is about 1:4. 1 :5, 1:6, 1:7, 1:8, 1:9, orabout 1:10, or any ratio therebetween.

[0150] Regarding prodrug potential of a pharmaceutical compound, or a salt thereof, is identified but is without an ionizable nitrogen (e.g., steroid drugs) any natural or synthetic aminoacid comprising a basic or neutral nitrogen may be esterified as a prodrug moiety . In someembodiments, the amino acid may be a proline, which has a neutral nitrogen atom susceptible to protonation, as illustrated in FIG.4. Proline provides an ionizable nitrogen (pKa of about 10.6) that, when protonated, acts as a counterion to the complexing agent, such that the protonated pro-drug is the pharmaceutical compound complexed to the complexing agent. In some embodiments, the complexing agent is SBEBCD.

[0151] In some embodiments, the composition comprises pharmaceutical compound comprising a prodrug pharmaceutical compound. In some embodiments, the prodrug comprises an active pharmaceutical conjugated to a chemical moiety via an ester bond. In some embodiments, the chemical moiety comprises an ionizable nitrogen. In some embodiments, the chemical moiety comprises an amino acid. In some embodiments, the amino acid is proline, lysine, arginine, or a combination or two or more thereof.

[0152] In some embodiments, the composition comprises a first pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof, comprising a first prodrug. In some embodiments, the first prodrug comprises a first API conjugated to a first chemical moiety. In some embodiments, the first chemical moiety comprises an amino acid, and the first chemical moiety is bound to the first API through an ester bond. In some embodiments, the composition comprises the second pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof, comprising a second prodrug. In some embodiments, the second prodrug comprises a second API conjugated to a second chemical moiety. In some embodiments, the second chemical moiety comprises an amino acid, and the second chemical moiety is bound to the second API through an ester bond. In some embodiments, the first prodrug and the second prodrug are the same. In some embodiments, the first prodrug comprises a protonated nitrogen, and the second prodrug does not comprise a protonated nitrogen. In some embodiments, the first prodrug comprising the protonated nitrogen complexes with the complexing agent. In some embodiments, the complexing agent further comprises a non-polar region. In some embodiments, the non-polar region is a non-polar pore. In some embodiments, the additional molar equivalent of the unionized substance is complexed to the non-polar regionAttorney Docket No.: 53160-716.601 of the complexing agent. In some embodiments, the additional molar equivalent of the unionized substance is complexed to the non-polar pore of the complexing agent.

[0153] In some embodiments, the pharmaceutically acceptable salt comprises 0.1-20 molarequivalents of the unionized substance compared to the complexing agent. In someembodiments, the pharmaceutically acceptable salt comprises 0.2-15 molar equivalents of unionized substance compared to the complexing agent. In some embodiments, the pharmaceutically acceptable salt comprises 0.5-10 molar equivalents of the unionized substance compared to the complexing agent. In some embodiments, the pharmaceutically acceptable salt comprises 1-5 molar equivalents of the unionized substance compared to the complexing agent. In some embodiments, the pharmaceutically acceptable salt comprises 0.1-20 molar equivalents of the unionized substance compared to the complexing agent, e.g., about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9,5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1,7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 9.0, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, 10.0, 10.1, 10.2, 10.3, 10.4, 10.5, 10.6, 10.7, 10.8, 10.9, 11.0, 11.1, 11.2, 11.3, 11.4, 11.5, 11.6, 11.7, 11.8, 11.9, 12.0, 12.1, 12.2, 12.3, 12.4, 12.5, 12.6, 12.7, 12.8, 12.9, 13.0, 13.1, 13.2, 13.3, 13.4, 13.5, 13.6, 13.7, 13.8, 13.9, 14.0, 14.1, 14.2, 14.3, 14.4, 14.5,14.6, 14.7, 14.8, 14.9, 15.0, 15.1, 15.2, 15.3, 15.4, 15.5, 15.6, 15.7, 15.8, 15.9 , 16.0, 16.1, 16.2,16.3, 16.4, 16.5, 16.6, 16.7, 16.8, 16.9, 17.0, 17.1, 17.2, 17.3, 17.4, 17.5, 17.6, 17.7, 17.8, 17.9, 18.0, 18.1, 18.2, 18.3, 18.4, 18.5, 18.6, 18.7, 18.8, 18.9, 19.0, 19.1, 19.2, 19.3, 19.4, 19.5, 19.6, 19.7, 19.8, 19.9, or 20.0 molar equivalents of the unionized substance, or any amount therebetween. In some embodiments, the pharmaceutically acceptable salt comprises 1-2 molarequivalents of the unionized substance compared to the complexing agent. In someembodiments, the pharmaceutically acceptable salt comprises about 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, or about 2 molar equivalents of the unionized substance compared to the complexing agent.

[0154] In some embodiments, the molar ratio of the cyclodextrin to the pharmaceutical compound comprising a protonated nitrogen atom is from about 1:4 to about 1:8. In some embodiments, the molar ratio of the cyclodextrin to the pharmaceutical compound comprising a protonated nitrogen atom is from about 1:4 to about 1:10. In some embodiments, the molar ratio of the cyclodextrin to the pharmaceutical compound comprising a protonated nitrogen atom is from about 1:5 to about 1:7. In some embodiments, the molar ratio of the cyclodextrin to the pharmaceutical compound comprising a protonated nitrogen atom is about 1:4. In someAttorney Docket No.: 53160-716.601 embodiments, the molar ratio of the cyclodextrin to the pharmaceutical compound comprising a protonated nitrogen atom is about 1:5. In some embodiments, the molar ratio of the cyclodextrin to the pharmaceutical compound comprising a protonated nitrogen atom is about 1:6. In some embodiments, the molar ratio of the cyclodextrin to the pharmaceutical compound comprising a protonated nitrogen atom is about 1:7. In some embodiments, the molar ratio of the cyclodextrin to the pharmaceutical compound comprising a protonated nitrogen atom is about 1:8. In some embodiments, the molar ratio of the cyclodextrin to the pharmaceutical compound comprising a protonated nitrogen atom is about 1:9. In some embodiments, the molar ratio of the cyclodextrinto the pharmaceutical compound comprising a protonated nitrogen atom is about 1:10.

[0155] In some embodiments, molar ratio of acidic functional groups of the complexing agent to the pharmaceutical compound comprising a protonated nitrogen atom is from about 2:1 to about 1:2. In some embodiments, molar ratio of acidic functional groups of the complexing agent to the pharmaceutical compound comprising a protonated nitrogen atom is from about 1.75:1 to about 1:1.75. In some embodiments, molar ratio of acidic functional groups of the complexing agent to the pharmaceutical compound comprising a protonated nitrogen atom is from about 1.5:1 to about 1:1.5. In some embodiments, molar ratio of acidic functional groups of the complexing agent to the pharmaceutical compound comprising a protonated nitrogen atom is from about 1.4:1 to about 1:1.4. In some embodiments, molar ratio of acidic functional groups of the complexing agent to the pharmaceutical compound comprising a protonated nitrogen atom is from 1.3:1 to about 1:1.3. In some embodiments, molar ratio of acidic functional groups of the complexing agent to the pharmaceutical compound comprising a protonated nitrogen atom is from about 1.25:1 to about 1:1.25. In some embodiments, molar ratio of acidic functional groups of the complexing agent to the pharmaceutical compound comprising a protonated nitrogen atom is from about 1.2:1 to about 1:1.2. In some embodiments, molar ratio of acidic functional groups of the complexing agent to the pharmaceutical compound comprising a protonated nitrogen atom is from about 1.15:1 to about 1:1.15. In some embodiments, molar ratio of acidic functional groups of the complexing agent to the pharmaceutical compound comprising a protonated nitrogen atom is from about 1.1:1 to about 1:1.1. In some embodiments, molar ratio of acidic functional groups of the complexing agent to the pharmaceutical compound comprising a protonated nitrogen atom is from about 1.05:1 to about 1:1.05. In some embodiments, molar ratio of acidic functional groups of the complexing agent to the pharmaceutical compound comprising a protonated nitrogen atom is about 1:1.

[0156] In some embodiments, the solubility of the ununionized substance in the pharmaceutically acceptable salt is higher than (i) the solubility of the unionized substance as aAttorney Docket No.: 53160-716.601 salt; or (ii) the solubility of the unionized substance in a salt comprising the unionized substance in freebase form that is complexing to a non-polar pore of the complexing agent, wherein the unionized substance has the same concentration in the pharmaceutically acceptable salt, the unionized substance as a salt, and the salt comprising the unionized substance in freebase form. In some embodiments, the solubility of the unionized substance in the pharmaceutically acceptable salt is higher than the solubility of the unionized substance in a salt comprising the unionized substance and complexing agent with a higher molar ratio of the unionized substance to the complexing agent, wherein the unionized substance has the same concentration in the pharmaceutically acceptable salt and the salt with a higher molar ratio of the unionized substance to the complexing agent. In some embodiments, the solubility of the unionizedsubstance in the pharmaceutically acceptable salt has an increase of at least 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 15-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, or 100-fold compared with (i) the solubility of the unionized substance as a salt; or (ii) the solubility of the unionized substance in a salt comprising the unionized substance in freebase form that is complexing to a non-polar pore of the complexing agent, wherein the unionized substance has the same concentration in the pharmaceutically acceptable salt, the unionized substance as a salt, and the salt comprising the unionized substance in freebase form. In some embodiments, the solubility of the unionized substance in the pharmaceutically acceptable salt has an increase of at least 2-fold, 3-fold, 4-fold, 5-fold, 6- fold, 7-fold, 8-fold, 9-fold, 10-fold, 15-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, or 100-fold compared with the solubility of the unionized substance in a salt comprising the unionized substance and complexing agent with a higher molar ratio of the unionized substance to the complexing agent, wherein the unionized substance has the same concentration in the pharmaceutically acceptable salt and the salt with a higher molar ratio of the unionized substance to the complexing agent.

[0157] In an aspect, provided herein is a pharmaceutically acceptable salt of a compound pharmaceutical comprising: (i) a first pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate orhydrate thereof, wherein the pharmaceutical compound comprises a protonated nitrogen atomand the pharmaceutical compound has a pKa of about 1 to about 7 ; (ii) a conjugate base of acomplexing agent comprising a plurality of acidic functional groups, wherein at least one acidic functional group of the plurality of acidic functional groups acts as a counterion of the first pharmaceutical compound; and (iii) a second pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt,Attorney Docket No.: 53160-716.601 solvate or hydrate thereof, wherein the second pharmaceutical compound is unionized. In some embodiments, the pharmaceutically acceptable salt has a ratio of the conjugate base of the complexing agent to the first pharmaceutical compound that is from about 1:4 to about 1:10. In some embodiments, the pharmaceutically acceptable salt has a ratio of the conjugate base of the complexing agent to the first pharmaceutical compound that is about 1:4.1:5, 1:6, 1:7, 1:8, 1:9, or about 1:10, or any ratio therebetween. In some embodiments, the pharmaceutically acceptable salt has a ratio of the conjugate base of the complexing agent to the second pharmaceutical compound that is about 1:1. In some embodiments, the first pharmaceutical compound comprises an ionized form. In some embodiments, the first pharmaceutical compound comprises an unionized form. In some embodiments, the second pharmaceutical compound does not comprise an ionizable nitrogen atom. In some embodiments, the second pharmaceutical compound has a pKa value above a threshold value. In some embodiments, the first pharmaceutical compound and the second pharmaceutical compound are the same. In some embodiments, the first pharmaceutical compound and the second pharmaceutical compound are different.

[0158] In some embodiments, the complexing agent is sulfobutylether-β-cyclodextrin. In some embodiments, the first pharmaceutical compound comprises a dissociative medication compound, a dissociative hallucinogen compound, a dissociative anesthetic compound, an arylcyclo-hexylamine, a 1,2-diarylethylamine, a β-keto-arylcyclohexylamine, or a compound that modulates the NMDA receptor. In some embodiments, the first pharmaceutical compound is ketamine, arylcyclo-hexylamine, 1,2-diarylethylamine, β-keto-arylcyclohexylamine, methoxetamine, deschloroketamine, N-ethyl-deschloroketamine (eticyclidone), 3- methoxyphencyclidine, methoxieticyclidine, ephenidine, lanicemine, dextromethorphan, dextrorphan, methoxyketamine, a N,N-dimethyltryptamine, a N,N-diethyltryptamine, a N,N- dipropyltryptamine, a N-methyl-N-propyltryptamine, a N-methyl-N-isopropyltryptamine, a N,N-diallyltryptamine, a N-methyl-N-allyltryptamine, N-methyl-N-ethyltryptamine, a N,N- Diisopropyltryptamine, 4-hydroxy-N-methyl-N-ethyltryptamine, 5-methoxy-N,N- diisopropyltryptamine, O-acetylpsilocin, methylisopropyllysergamide, ethylisopropyllysergamide, 6-allyl-6-nor-LSD, 6-ethyl-6-nor-lysergic acid diethylamide, 1- acetyl-LSD, 1-propionyl-6-ethyl-6-nor-lysergic acid diethylamide, 1-propionyl-lysergic acid diethylamide, 1-Cyclopropionyl-d-lysergic acid diethylamide, N1-butyryl-lysergic acid diethylamide, 6-propyl- 6-nor- Lysergic acid diethylamide, mescaline, 2,5-dimethoxy-4- bromophenethylamine (2C-B), 2-(4-Iodo-2,5-dimethoxyphenyl)ethan-1-amine (2C-I), 2-(4- Chloro-2,5-dimethoxyphenyl)ethan-1-amine (2C-C), 2,5-Dimethoxy-4-iodoamphetamine, 2-Attorney Docket No.: 53160-716.601 [2,5-Dimethoxy-4-(propylsulfanyl)phenyl]ethan-1-amine, 2-(4-iodo-2,5-dimethoxyphenyl)-N- [(2-methoxyphenyl)methyl]ethanamine, racemorphan, levorphanol, racemethorphan, buprenorphine, morphine, loperamide, morphine, codeine, hydrocodone, oxymorphone, buprenorphine, fentanyl, methadone, tramadol, alpha-methyl acetyl fentanyl, alfentanil, butyryl fentanyl, butyrfentanyl, carfentanil, 3-methylcarfentanil, 4-fluorofentanyl, beta-hydroxyfentanyl, alpha-methylfentanyl, cis-3-methylfentanyl, beta-hydroxy-3-methylfentanyl, remifentanil, sufentanil, 3-methylthiofentanyl, naloxone, naltrexone, a cathinone, a 3,4- methylenedioxyamphetamine derivative, an aminoalkyl-substituted benzofuran, a substituted amphetamine, an aminoindane, diphenhydramine, hydroxazine, phenylephrine, dopamine,adrenaline, lidocaine, oxymetazoline, clemastine, chlorpheniramine, and 6 -chloro-2-aminotetralin. In some embodiments, the first pharmaceutical compound comprises ketamine.

[0159] In some embodiments, the second pharmaceutical compound comprises rapamycin. In some embodiments, the first pharmaceutical compound comprises ketamine and the second pharmaceutical compound comprises rapamycin. In some embodiments, the first pharmaceutical compound comprises no ketamine and the second pharmaceutical compound comprises rapamycin. In some embodiments, the second pharmaceutical compound comprises clonidine. In some embodiments, the first pharmaceutical compound comprises ketamine and the second pharmaceutical compound comprises clonidine. In some embodiments, the first pharmaceutical compound comprises no ketamine and the second pharmaceutical compound comprises clonidine. In some embodiments, the complexing agent comprises a substituted cyclodextrin. In some embodiments, the complexing agent comprises a cyclodextrin substituted with at least one acidic functional group. In some embodiments, the cyclodextrin is substituted with 3 to 8 acidic functional groups. In some embodiments, the cyclodextrin is sulfobutylether-β-cyclodextrin. In some embodiments, the pharmaceutically acceptable salt is formulated for subcutaneous, intramuscular, sublingual, oral, rectal, transvaginal, or intranasal administration. In some embodiments, the complexing agent comprises a non-polar region. In some embodiments, the second pharmaceutical compound is complexed to the complexing agent through the non-polar region.

[0160] In some embodiments, the first pharmaceutical compound comprises a GABA-ergic, an alpha-2 agonist, an ophthalmic, a bisphosphonate, an antibiotic, an anticoagulant or an thrombolytic, an antifungal, an antineoplastic, an antiviral a cardiovascular medication, a central nervous system depressant, a central nervous system stimulant, a local anesthetic, an anti- nausea, an anti-migraine, an anti-Parkinson’s medication, an antihistamine, a H2 histamine receptor blocker, an opioid, a tyrosine kinase inhibitor, or a combination thereof. In someAttorney Docket No.: 53160-716.601 embodiment, the antifungal comprises an azole antifungal. In some embodiments, the first pharmaceutical compound comprises a GABA-ergic. In some embodiments, the GABA-ergic comprises Baclofen, Gaboxidol, or Muscimol, or a combination thereof. In some embodiments, the first pharmaceutical compound comprises an alpha-2 agonist. In some embodiments, the alpha-2 agonist comprises Clonidine, Guanfacine, or Tizanidine, or a combination thereof. In some embodiments, the first pharmaceutical compound comprises an ophthalmic. In some embodiments, the ophthalmic comprises Aceclidine, Atropine, Azelastine, Brimonidine, Cyclopentolate, Ketotifen, Levobunolol, Olopatadine, Pilocarpine, Proparacaine, Tetracaine, Timolol, or Tropicamide, or a combination thereof. In some embodiments, the first pharmaceutical compound comprises a bisphosphonate. In some embodiments, the bisphosphonate comprises Alendronate, Ibandronate, Pamidronate, Risedronate, or Zoledronic acid, or a combination thereof. In some embodiments, the first pharmaceutical compound comprises an anticoagulant or a thrombolytic. In some embodiments, the anticoagulant or the thrombolytic comprises Alteplase, Argatroban, Bivalirudin, Fondaparinux, Lepirudin, Streptokinase, or Urokinase, or a combination thereof. In some embodiments, the first pharmaceutical compound comprises an antineoplastic. In some embodiments, the antineoplastic comprises Bleomycin, Busulfan, Cisplatin, Dacarbazine, Daunorubicin, Doxorubicin, Epirubicin, Etoposide, Gemcitabine, Idarubicin, Ixabepilone, Lapatinib, Mesna, Mitomycin C, Paclitaxel, Pemetrexed, Rituximab, Temsirolimus, Trastuzumab, Venitoclax, or Vinblastine, Vincristine, or a combination thereof. In some embodiments, the first pharmaceutical compound comprises a cardiovascular medication. In some embodiments, the cardiovascular medication comprises Bretylium, Dobutamine, Dopexamine, Epoprostenol, Esmolol, Iloprost, Nesiritide, Nitroglycerin, Norepinephrine, or Phenylephrine, or a combination thereof. In some embodiments, the first pharmaceutical compound comprises a nervous system medication such as, for example, a central nervous system medication. In some embodiments, the nervous system medication comprises a central nervous system depressant. In some embodiments, the pharmaceutical composition comprises a central nervous system stimulant. In some embodiments, the pharmaceutical composition comprises a central nervous system depressant such as, for example, Alprazolam, Chlordiazepoxide, Clonazepam, Diazepam, Dexmedetomidine, Dextromethorphan, Flurazepam, Gabapentin, Ketamine, Lorazepam, Midazolam, Oxazepam, Propofol, Temazepam, or Triazolam, or a combination thereof. In some embodiments, the first pharmaceutical compound comprises a central nervous system, such as, for example, Amphetamine, Cocaine, Dexmethylphenidate, Dextroamphetamine, Ephedrine, Lisdexamfetamine, Methamphetamine, Methylphenidate, Modafinil, Phenylephrine,Attorney Docket No.: 53160-716.601 Pseudoephedrine, Sibutramine, or a combination thereof. In some embodiments, the first pharmaceutical compound comprises a local anesthetic. In some embodiments, the local anesthetic comprises Articaine, Benzocaine, Bupivacaine, Chloroprocaine, Cocaine, Dibucaine, Etidocaine, Levobupivacaine, Lidocaine, Mepivacaine, Prilocaine, Procaine, Proparacaine, Ropivacaine, or Tetracaine, or a combination thereof. In some embodiments, the first pharmaceutical compound comprises an anti-nausea. In some embodiments, the anti-nausea comprises Dolasetron, Granisetron, Ondansetron, or Palonosetron, or a combination thereof. In some embodiments, the first pharmaceutical compound comprises an anti-migraine. In some embodiments, the anti-migraine comprises Almotriptan, Avitriptan, Donitriptan, Eletriptan, Frovatriptan, Lasmiditan, Naratriptan, Rizatriptan, Sumatriptan, or Zolmitriptan, or a combination thereof. In some embodiments, the first pharmaceutical compound comprises an anti-Parkinson’s medication. In some embodiments, the anti-Parkinson’s medication comprises Amantadine, Apomorphine, Benztropine, Benserazide, Bromocriptine, Cabergoline, Carbidopa, Entacapone, Foscarbidopa, Foslevodopa, Levodopa, Melvodopa, Pramipexole, Rasagiline, Ropinirole, Rotigotine, Safinamide, Selegiline, Tolcapone, or Trihexyphenidyl, or a combination thereof. In some embodiments, the first pharmaceutical compound comprises an antihistamine. In some embodiments, the antihistamine comprises Acrivastine, Brompheniramine, Cetirizine, Chlorpheniramine, Clemastine, Cyproheptadine, Desloratadine, Dexchlorpheniramine, Diphenhydramine, Doxylamine, Fexofenadine, Hydroxyzine, Levocetirizine, Loratadine, Meclizine, Promethazine, or Tripelennamine, or a combination thereof. In some embodiments, the first pharmaceutical compound comprises an H2 Histamine receptor blocker. In some embodiments, the H2 histamine receptor blocker comprises Cimetidine, Famotidine, Nizatidine, or Ranitidine, or a combination thereof. In some embodiments, the first pharmaceutical compound comprises an inhibitor, such as a tyrosine kinase inhibitor, such as, for example, Bosutinib, Dasatinib, Erlotinib, Gefitinib, Imatinib, Lapatinib, Nilotinib, Ponatinib, Sorafenib, or Sunitinib, or a combination thereof. In some embodiments, the first pharmaceutical compound comprises Amifampridine, Amifostine, Aminocaproic acid, Argatroban, Asenapine, Atropine, Bivalirudin, Cisatracurium, Deferoxamine, Desmopressin, Gabapentin, Lurasidone, Milrinone, Nicotine, Octreotide, Pregabalin, Rocuronium, Terbutaline, Tirofiban, Tranexamic acid, Vecuronium, or Nepafenac, or a combination thereof.

[0161] In some embodiments, the solubility of the second pharmaceutical compound in the pharmaceutically acceptable salt is higher than the solubility of the second pharmaceutical compound as a salt, wherein the second pharmaceutical compound has the same concentration in the pharmaceutically acceptable salt, and the second pharmaceutical compound as a salt. InAttorney Docket No.: 53160-716.601 some embodiments, the solubility of the second pharmaceutical compound in the pharmaceutically acceptable salt has an increase of at least 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 15-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80- fold, 90-fold, or 100-fold compared with the solubility of the second pharmaceutical compound as a salt, wherein the second pharmaceutical compound has the same concentration in the pharmaceutically acceptable salt, and the second pharmaceutical compound as a salt.

[0162] In some embodiments, the plurality of acidic functional groups comprise an acidic group which acts as a counterion for the protonated nitrogen atom of the pharmaceutical compound. In some embodiments, the acidic group is the conjugate base of the acidic group. In some embodiments, the acidic group is a carboxylic acid or carboxylate. In some embodiments, the acidic group is a carboxylate. In some embodiments, the acidic group is a sulfonic acid or sulfonate. In some embodiments, the acidic group is a sulfonate. In some embodiments, the conjugate base of the complexing agent acts as the counterion for a plurality of the pharmaceutical compound. In some embodiments, each acidic group of the plurality of acidic functional groups acts as a counterion for a plurality of the pharmaceutical compound In some embodiments, each acidic group of the plurality of acidic functional groups acts as a counterion for a protonated amine of a plurality of the pharmaceutical compound. In some embodiments,each of the plurality of acidic functional groups acts as a counterion for a pronated amine.

[0163] In some embodiments, the complexing agent is a cyclodextrin substituted with the plurality of acidic functional group. In some embodiments, the plurality of acidic functional groups is a carboxylic acid, sulfonic acid, sulfonic acid, phosphonic acid, or phosphonic acid, or any combination thereof. In some embodiments, the cyclodextrin is substituted with at least 1, at least 2, at least 3, at least 4, at least 5, or at least 6 acidic functional groups. In some embodiments, the cyclodextrin is substituted with 3 to 8 acidic functional groups, 3 to 7 acidic functional groups, 4 to 8 acidic functional groups, 4 to 7 acidic functional groups, 5 to 8 acidicfunctional groups, 6 to 8 acidic functional groups, or 7 to 8 acidic functional groups.

[0164] In some embodiments, the complexing agent is a substituted cyclodextrin. In some cases, substituted cyclodextrins provided herein are complex mixtures wherein individual cyclodextrin molecules may comprise different numbers of substituents from other individual cyclodextrin molecules. In such cases, the number of substituents (e.g., the number of acidic functional groups) described as being present on the cyclodextrins provided herein may refer to an average degree of substitution of the mixture. For example, when a cyclodextrin is described as substituted with 3 to 8 acidic functional groups, it is intended that a complex mixture of cyclodextrins having an average degree of substitution from 3 to 8 acidic functional groups isAttorney Docket No.: 53160-716.601 covered. The average degree of substitution need not be an integer value and will often be a decimal value. For example, commercially available SBEBCD has an average degree of substitution of about 6.5.

[0165] In some embodiments, the complexing agent is a substituted cyclodextrin. In some embodiments, the substituted cyclodextrin is substituted with one or more acidic functional groups, or a pharmaceutically acceptable salt thereof. In some embodiments, the substituted cyclodextrin is substituted with a plurality of carboxylic acid, sulfonic acid, sulfonic acid, phosphonic acid, or phosphonic acid functional groups. In some embodiments, the cyclodextrin is substituted with at least 1, at least 2, at least 3, at least 4, at least 5, or at least 6 acidic functional groups. In some embodiments, the cyclodextrin is substituted with 3 to 8 acidic functional groups, 3 to 7 acidic functional groups, 4 to 8 acidic functional groups, 4 to 7 acidic functional groups, 5 to 8 acidic functional groups, 6 to 8 acidic functional groups, or 7 to 8 acidic functional groups.

[0166] In some embodiments, the molar ratio of the cyclodextrin to the pharmaceutical compound comprising a protonated nitrogen atom is from about 1:4 to about 1:8. In some embodiments, the molar ratio of the cyclodextrin to the pharmaceutical compound comprising a protonated nitrogen atom is from about 1:4 to about 1:10. In some embodiments, the molar ratio of the cyclodextrin to the pharmaceutical compound comprising a protonated nitrogen atom is from about 1:5 to about 1:7. In some embodiments, the molar ratio of the cyclodextrin to the pharmaceutical compound comprising a protonated nitrogen atom is about 1:4. In some embodiments, the molar ratio of the cyclodextrin to the pharmaceutical compound comprising a protonated nitrogen atom is about 1:5. In some embodiments, the molar ratio of the cyclodextrin to the pharmaceutical compound comprising a protonated nitrogen atom is about 1:6. In some embodiments, the molar ratio of the cyclodextrin to the pharmaceutical compound comprising a protonated nitrogen atom is about 1:7. In some embodiments, the molar ratio of the cyclodextrin to the pharmaceutical compound comprising a protonated nitrogen atom is about 1:8. In some embodiments, the molar ratio of the cyclodextrin to the pharmaceutical compound comprising a protonated nitrogen atom is about 1:9. In some embodiments, the molar ratio of the cyclodextrin to the pharmaceutical compound comprising a protonated nitrogen atom is about 1:10.

[0167] In some embodiments, molar ratio of acidic functional groups of the complexing agent to the pharmaceutical compound comprising a protonated nitrogen atom is from about 2:1 toabout 1:2. In some embodiments, molar ratio of acidic functional groups of the co mplexingagent to the pharmaceutical compound comprising a protonated nitrogen atom is from about 1.75:1 to about 1:1.75. In some embodiments, molar ratio of acidic functional groups of theAttorney Docket No.: 53160-716.601 complexing agent to the pharmaceutical compound comprising a protonated nitrogen atom is from about 1.5:1 to about 1:1.5. In some embodiments, molar ratio of acidic functional groups of the complexing agent to the pharmaceutical compound comprising a p...

Claims

Attorney Docket No.: 53160-716.601 CLAIMS WHAT IS CLAIMED IS:

1. A pharmaceutical composition, comprising: (i) a pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof, wherein the pharmaceutical compound comprises a protonated nitrogen atom and has a pKa of about 1 to about 7.5; and (ii) a complexing agent, wherein the complexing agent is an acid-substituted cyclodextrin comprising a plurality of acidic functional groups comprising an acidic group which acts as a counterion for the protonated nitrogen atom of the pharmaceutical compound, wherein the pharmaceutical composition has a molar ratio of the complexing agent to the pharmaceutical compound that is from about 1:1 to about 1:

10.

2. A pharmaceutical composition, comprising: (i) a pharmaceutical compound, an enantiomer, or an isotopic variant thereof, wherein the pharmaceutical compound comprises a protonated nitrogen atom and has a pKa of at least 1; and (ii) a complexing agent, wherein the complexing agent is an acid-substituted cyclodextrin comprising a plurality of acidic functional groups comprising an acidic group which acts as a counterion for the protonated nitrogen atom of the pharmaceutical compound, wherein the pharmaceutical composition has a molar ratio of the complexing agent to the pharmaceutical compound that is from about 1:1 to about 1:

10.

3. A pharmaceutical composition, comprising: (i) a pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof, wherein the pharmaceutical compound comprises a protonated nitrogen atom and has a pKa of about 1 to about 13; and (ii) a complexing agent, wherein the complexing agent is an acid-substituted cyclodextrin comprising a plurality of acidic functional groups comprising an acidic groupwhich acts as a counterion for the protonated nitrogen atom of the pharmaceutical compou nd,wherein the pharmaceutical composition has a molar ratio of the complexing agent to thepharmaceutical compound that is from about 1:1 to about 1:10.

4. A pharmaceutical composition, comprising: (i) a pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof, wherein the pharmaceutical compound comprises a protonated nitrogen atom and has a pKa of about 4 to about 13; andAttorney Docket No.: 53160-716.601 (ii) a complexing agent, wherein the complexing agent is an acid-substituted cyclodextrin comprising a plurality of acidic functional groups comprising an acidic group which acts as a counterion for the protonated nitrogen atom of the pharmaceutical compound, wherein the pharmaceutical composition has a molar ratio of the complexing agent to thepharmaceutical compound that is from about 1:1 to about 1:10.

5. The pharmaceutical composition of any one of claims 1-4, wherein the complexing agent comprises a substituted cyclodextrin.

6. The pharmaceutical composition of any one of claims 1-5, wherein the complexing agentcomprises a cyclodextrin substituted with at least one acidic functional group.

7. The pharmaceutical composition of any one of claims 1-6, wherein the cyclodextrin is substituted with 3 to 8 acidic functional groups.

8. The pharmaceutical composition of any one of claims 1-7, wherein the cyclodextrin is sulfobutylether-β-cyclodextrin (SBEBCD).

9. The pharmaceutical composition of any one of claims 1-8, wherein the pharmaceutical compound has a pKa of at least 1.

10. The pharmaceutical composition of any one of claims 1-9, wherein the pharmaceutical compound has a pKa of about 1 to about 7.

5.

11. The pharmaceutical composition of any one of claims 1-10, wherein the pharmaceutical compound has a pKa of about 1 to about 5.

12. The pharmaceutical composition of any one of claims 1-11, wherein the pharmaceutical compound has a pKa of about 7.5 to about 13.

13. The pharmaceutical composition of any one of claims 1-12, wherein the pharmaceutical compound comprises a 5'-deoxyribonucleoside, 6,7-benzomorphan, ajmaline-sarpagine alkaloid, alkaline earth metal organide, amaryllidaceae alkaloid, anthracene, anthracycline, aporphine, azaspirodecane, azepane, azobenzene, azole, azolidine, azoline, benzazepine, benzene and substituted, benzimidazole ribonucleosides and ribonucleotide, benzimidazole, benzocycloheptapyridine, benzodiazepine, benzodioxane, benzodioxole, benzofuran, benzopyran, benzopyrazole, benzothiadiazole, benzothiazepine, benzothiazine, benzothiazole, benzothiepin, benzothiophene, benzothiopyran, benzotriazole, benzoxadiazole, benzoxazepine, benzoxazine, benzoxepine, biotin, camptothecin, carboxylic acid, cephalotaxus alkaloid, cinchona alkaloid, cinnamic acid, coumaran, cycloheptathiophene, depsides and depsidone, diarylheptanoid, diazanaphthalene, diazinane, diazine, dibenzocycloheptene, dioxane, epoxide, ergoline, fatty acyl, flavin nucleotide, flavonoid, fluorene, furan, furopyran, glycerophospholipid, homogeneous other non-metal compound, hydroxy acid, ibogan-typeAttorney Docket No.: 53160-716.601 alkaloid, imidazodiazepine, imidazole ribonucleosides and ribonucleotide, imidazopyridine, imidazopyrimidine, imidazothiazole, indane, indenes and isoindene, indole, indolizidine, isocoumaran, isoindole, isoquinoline, lactam, linear 1,3-diarylpropanoid, lupin alkaloid, macrolactam, macrolide lactam, macrolides morphinan, naphthacene, naphthalene, naphthofuran, naphthopyran, nucleoside and nucleotide analogue, organic carbonic acid, organic phosphine, organic phosphonic acid, organic sulfonic acid, organonitrogen compound, organooxygen compound, organothiophosphorus compound, oxazinane, peptidomimetic, phenanthrene, phenanthroline, phenol ester, phenol ether, phenol, phenylpropanoic acid, phthalide isoquinoline, piperazinoazepine, piperidine, polypeptide, prenol lipid, pteridine, purine nucleoside, purine nucleotide, pyrazolopyridine, pyrazolopyrimidine, pyridine, pyridopyrimidine, pyrimidine nucleoside, pyrrole, pyrrolidine, pyrrolopyrazine, pyrrolopyridine, pyrrolopyrimidine, quinoline, steroids and steroid, stilbene, tetracycline, tetrahydroisoquinoline, tetralin, thiadiazine, thienodiazepine, thienopyridine, thienothiazine, thiochromene, thioether, thiol, thiophene, transition metal salt, triazinane, triazine, triazole ribonucleosides and ribonucleotide, triazolopyrimidine, triphenyl compound, tropane alkaloid, vinca alkaloid, yohimbine alkaloid, or a derivative thereof, or a combination thereof.

14. The pharmaceutical composition of any one of claims 1-11, wherein the pharmaceutical compound has a pKa of about 1 to about 2.

15. The pharmaceutical composition of claim 14, wherein the pharmaceutical compound comprises a 1,4-benzodiazepine, amine, amino acid, peptide, androstane steroid, benzenesulfonamide, benzoic acids, benzophenone, benzothiadiazine, biphenyls, carboxylic acid derivative, depsipeptide, diphenylmethane, ether, halobenzene, isoindoline, nitrogen mustard compound, nitroquinolines, purine 2’-deoxyribonucleoside, purines, pyrazole, pyrimidines orderivative thereof, retinoid, substituted pyrrole, or a combination thereof.

16. The pharmaceutical composition of claim 15, wherein the pharmaceutical compound comprises apadenoson, asunaprevir, azilsartan medoxomil, benzthiazide, bromfenac, candesartan cilexetil, carbazochrome, chlorambucil, chlorothiazide, cladribine, clofarabine, clonazepam, CVT-6883, CX516, dacarbazine, diazoxide, emodepside, fimasartan, flubendazole, flucytosine, fludiazepam, flunitrazepam, ganciclovir, gliclazide, glisoxepide, grazoprevir, guanosine, ibudilast, ibuproxam, iocetamic acid, iopamidol, iopanoic acid, isatoribine, ixazomib, MB-07803, nateglinide, nepafenac, OPC-51803, pleconaril, pomalidomide, pralnacasan, pyrvinium, regadenoson, rimonabant, selexipag, simeprevir, sulfadimethoxine, sulfamerazine,sulfameter, sulfamethizole, sulfamethoxazole, sulfametopyrazine, sulfamoxole, ta ranabant,tazarotene, tiopronin, tolazamide, trapidil, uracil mustard, or a combination thereof.Attorney Docket No.: 53160-716.601 17. The pharmaceutical composition of any one of claims 1-11, wherein the pharmaceutical compound has a pKa of about 2 to about 3.

18. The pharmaceutical composition of claim 17, wherein the pharmaceutical compound comprises azobenzene, azole, benzazepine, benzene, benzodiazepine, benzothiazine,benzothiazole, carboxylic acid, depside, diazanaphthalene, diazine, imidazopyrimidine, indole,isoindole, lactam, macrolides naphthalene, nucleoside and nucleotide analogue, organooxygen compound, piperidine, prenol lipid, pteridine, purine nucleoside, purine nucleotide,pyrazolopyrimidine, pyridine, pyrimidine nucleoside, pyrrolopyridine, quinolin e, steroid,thienodiazepine, triazine, triazolopyrimidine, or a combination thereof.

19. The pharmaceutical composition of claim 18, wherein the pharmaceutical compoundcomprises 1,4-benzodiazepines, amino acids or peptides, aminotriazines, androstane steroids ,anilides, aniline and substituted anilines, benzazepines, benzenesulfonamides, benzenesulfonyl compounds, benzodiazines, benzoic acids and derivatives, beta lactams, biphenyls and derivatives, carbazoles, diphenylethers, diphenylmethanes, epothilones estrane steroids, ethers, halobenzenes, isoindolines, milbemycins, monoterpenoids, nitroquinolines and derivatives, oxosteroids, phenoxyacetic acid derivatives, phenylbutylamines, phenylcarbamic acid esters, phenylmethylamines, phenylpropanes, phenylquinolines, pterins and derivatives, purine 2',3'- dideoxyribonucleosides, purine ribonucleotides, purines and purine derivatives, pyrazoles, pyrazolo[3,4-d]pyrimidines, pyridinecarboxylic acids and derivatives, pyrimidines and pyrimidine derivatives, sulfanilides, or a combination thereof.

20. The pharmaceutical composition of claim 18 or 19, wherein the pharmaceutical compound comprises aciclovir, adipiplon, alisertib, allopurinol, ambrisentan, amelubant, aminobenzoic acid, aminopterin, aminosalicylic acid, amprenavir, anastrozole, arsanilic acid, asoprisnil, benzocaine, BMS-488043, brecanavir, bromazepam, bumetanide, butamben, cangrelor, cefixime, cefpiramide, chromium picolinate, cidofovir, ciluprevir, cinalukast, clazosentan, clotiazepam, cloxazolam, dabrafenib, dapsone, darunavir, delorazepam, diazepam, didanosine, dutasteride, edotecarin, efonidipine, elacytarabine, entecavir, epirizole, epothilone d, finasteride, fluconazole, flutemetamol (18F), folic acid, fomepizole, fosamprenavir, ganstigmine, GW-501516, halazepam, indocyanine green, inosine, iodamide, iopromide, isavuconazole, ixabepilone, KOS-1584, KP-1461, lenalidomide, letrozole, leucovorin, levoleucovorin, macitentan, meradimate, mercaptopurine, methotrexate, methylene blue, methylthioninium, motexafin gadolinium, motexafin lutetium, moxidectin, naxifylline, nitrazepam, nitroxoline, olaparib, ombitasvir, OT-551, padimate O, paritaprevir, patupilone, penciclovir, phenyl aminosalicylate, PPL-100, pralatrexate, quazepam, ravuconazole, regorafenib, regrelor,Attorney Docket No.: 53160-716.601 ritonavir, roflumilast, roxadustat, silver sulfadiazine, sorafenib, stanozolol, sulfabenzamide, sulfacetamide, sulfacytine, sulfadiazine, sulfadoxine, sulfamerazine, sulfamethazine, sulfanilamide, sulfaphenazole, sulfapyridine, sulfasalazine, sulfathiazole, sulfisoxazole, talnetant, tasosartan, technetium tc-99m disofenin, technetium tc-99m mebrofenin, tezosentan, ticagrelor, tirapazamine, troxacitabine, trypan blue, voriconazole, or a combination thereof.

21. The pharmaceutical composition of any one of claims 1-11, wherein the pharmaceutical compound has a pKa of about 3 to about 4.

22. The pharmaceutical composition of claim 21, wherein the pharmaceutical compound comprises a 1,4-benzodiazepine, amino acid, peptide, anilide, aniline and substituted aniline, anisole, aryl thioether, benzodiazine, benzofuranone, benzoic acids and derivative, benzophenone, beta lactam, biphenyls and derivative, bipyridines and oligopyridine,carbodiimide, diphenylether, diphenylmethane, epothilones estrane steroid, ether, haloquinoline ,hexacarboxylic acids and derivative, imidazole, isoindole, milbemycin, morpholine, phenoxyacetic acid derivative, phenylmethylamine, phenylpyridine, piperazine, pterins and derivative, purine 2’,3’-dideoxyribonucleoside, purines and purine derivative, purines and purine derivative, pyrazine, pyrazole, pyridine carboxaldehyde, pyridinecarboxylic acids and derivative, pyridinesulfonamide, pyridyltriazole, steroid ester, sulfanilide, sulfinylbenzimidazole, or a combination thereof.

23. The pharmaceutical composition of claim 21 or 22, wherein the pharmaceutical compound comprises adenosine, amiloride, aminobenzoic acid, aminophenazone, anagrelide, aprepitant, arsanilic acid, azathioprine, aztreonam, benzocaine, benzonatate, bisacodyl, bromazepam, brotizolam, bumetanide, butamben, calcium carbimide, cefepime, cefixime, cefmenoxime, cefotaxime, cefpodoxime, ceftizoxime, ceftriaxone, chloroxine, chromium picolinate, clioquinol, dabigatran etexilate, dabrafenib, dexlansoprazole, dexrazoxane, diazepam, didanosine, diiodohydroxyquinoline, entecavir, etofibrate, etravirine, ezogabine, flumazenil, flutemetamol (18F), indocyanine, inosine, inositol nicotinate, iopodic acid, irbesartan, isocarboxazid, isocarboxazid, isoniazid, itraconazole, ixabepilone, lansoprazole, leucovorin, levoleucovorin, levomefolic acid, lobeglitazone, losartan, lumacaftor, mazindol, mebendazole, mercaptopurine, mercaptopurine, methotrexate, metronidazole, metronidazole, montelukast, montelukast, moxidectin, nelarabine, niacin, nicorandil, nicotinamide, norelgestromin, norgestimate, oxfendazole, padimate o, pantoprazole, penciclovir, perampanel, picosulfuric acid, piroxicam, posaconazole, pralatrexate, prazepam, procaine merethoxylline, pyridoxal, pyridoxal phosphate, riociguat, ritonavir, stanozolol, talniflumate, tasosartan, tenofovir disoproxil,Attorney Docket No.: 53160-716.601 thiabendazole, thonzonium, ticagrelor, tinidazole, tioguanine, topiroxostat, torasemide, triamterene, triamterene, vemurafenib, vemurafenib, vismodegib, or a combination thereof.

24. The pharmaceutical composition of any one of claims 1-7, wherein the pharmaceutical compound has a pKa of about 4 to about 5.

25. The pharmaceutical composition of claim 24, wherein the pharmaceutical compound comprises a 1,4-benzodiazepine, 1-ribosyl-imidazolecarboxamide, 2-benzimidazolylcarbamic acid ester, 8-hydroxyquinoline, amine, amino acid, peptide, androstane steroid, anilide, aniline and substituted aniline, anthraquinone, aryl thioether, benzodiazine, benzoic acids and derivative, beta lactam, biphenyls and derivative, bipyridines and oligopyridine, bisphosphonate, carbonyl compound, diphenylmethane, ether, hexacarboxylic acids and derivative, imidazole, imidazoquinoline, indolequinone, naphthyridine, oxosteroid, phenethylamine, phenylbenzimidazole, phenylhydrazine, phenylpiperidine, phenylpyridine, phenylquinoline,pterins and derivative, purine ribonucleotide, purines and purine derivative, pyrazolo[1,5 -a]pyrimidine, pyridine carboxaldehyde, pyridinecarboxylic acids and derivative, pyridinesulfonamide, pyridoindole, quinoline carboxylic acid, styrene, sulfinylbenzimidazole, trifluoromethylbenzene, or a combination thereof.

26. The pharmaceutical composition of claim 24 or 25, wherein the pharmaceutical compound comprises azathioprine, abiraterone, acadesine, adenosine 5'-phosphosulfate, adenosine monophosphate, AICA ribonucleotide, albendazole, amfecloral, aminoglutethimide,aminohippuric acid, amrinone, atazanavir, aztreonam, banoxantrone, binodenoson , bisacodyl,carfilzomib, cefditoren, cefepime, cefmenoxime, cefotaxime, cefpodoxime, ceftazidime, ceftibuten, ceftizoxime, ceftriaxone, coenzyme A, dexlansoprazole, ensulizole, erlotinib, esomeprazole, estazolam, etizolam, etomidate, etoricoxib, etravirine, fiboflapon, flavin adenine dinucleotide, florbetaben (18F), florbetapir (18F), geldanamycin, gentian violet, hexocyclium, idelalisib, implitapide, indium In-111 oxyquinoline, inositol nicotinate, iopodic acid, irbesartan, lansoprazole, levosimendan, loratadine, lornoxicam, losartan, LX-2931, methoxyamine, metyrapone, mifepristone, milrinone, minoxidil, nalidixic acid, niacin, ocinaplon, omeprazole, OSI-930, oxibendazole, oxyquinoline, perampanel, piclidenoson, picosulfuric acid, pitavastatin, porfiromycin, PX-12, pyridoxal, pyridoxal phosphate, rabeprazole, repaglinide, resiquimod, retaspimycin, ridogrel, riluzole, risedronate, rivoglitazone, rosoxacin, S-8510, sapropterin, tecadenoson, tenofovir disoproxil, tenoxicam, thiabendazole, torasemide, triazolam, tucidinostat, ulipristal, varlitinib, vatalanib, verteporfin, verubulin, vidarabine, vipadenant, vorapaxar, or a combination thereof.Attorney Docket No.: 53160-716.601 27. The pharmaceutical composition of any one of claims 1-11, wherein the pharmaceutical compound has a pKa of about 5 to about 6.

28. The pharmaceutical composition of claim 27, wherein the pharmaceutical compound comprises a 1,4-benzodiazepine, 1-ribosyl-imidazolecarboxamide, 2-benzimidazolylcarbamic acid ester, 8-hydroxyquinoline, amine, amino acid, peptide, androstane steroid, anilide, aniline and substituted aniline, anthraquinone, aryl thioether, benzodiazine, benzoic acid, beta lactam, biphenyl, bipyridines and oligopyridine, bisphosphonate, diphenylmethane, ether, hexacarboxylic acid, imidazole, imidazoquinoline, indolequinone, naphthyridine, oxosteroid, phenethylamine, phenylbenzimidazole, phenylhydrazine, phenylpiperidine, phenylpyridine,phenylquinoline, pterin, purine ribonucleotide, purines and purine derivative, pyrazolo[1,5 -a]pyrimidine, pyridine carboxaldehyde, pyridinecarboxylic acid, pyridinesulfonamide, pyridoindole, quinoline carboxylic acid, styrene, sulfinylbenzimidazole, trifluoromethylbenzene, or a derivative thereof, or a combination thereof.

29. The pharmaceutical composition of claim 27 or 28, wherein the pharmaceutical compound comprises 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, 5- methyltetrahydrofolic acid, abacavir, adefovir dipivoxil, adenine, alprazolam, ALT-2074, amdoxovir, apilimod, adenosine triphosphate, avanafil, axitinib, azelnidipine, benazepril, benzimidazole, bicisate, biricodar dicitrate, brilliant green, cabozantinib, capravirine, carbidopa,cefapirin, cerivastatin, cilazapril, cisplatin, clevidipine, clonixin, clopidogrel, cocarboxylase,dapivirine, delamanid, dersalazine, dolasetron, elbasvir, enalapril, ethionamide, etifoxine, etozoline, famciclovir, felodipine, floctafenine, fominoben, fosaprepitant, GTS-21, hetacillin, imidacloprid, imiquimod, incadronic acid, indibulin, isosulfan blue, isradipine, kinetin, lamotrigine, ledipasvir, linsitinib, meclinertant, mesalazine, methenamine, moexipril, morniflumate, NADH, nevirapine, nifedipine, niflumic acid, nimodipine, nisoldipine, nitrendipine, olmesartan, pazopanib, peldesine, perindopril, phenelzine, picoplatin, pinacidil, pioglitazone, pipecuronium, pradefovir mesylate, prasugrel, prinomastat, procarbazine, pyridoxine, quinapril, ramipril, rilpivirine, rostaporfin, ruxolitinib, seliciclib, sildenafil, sonidegib, spirapril, stannsoporfin, talmapimod, taribavirin, temocapril, temoporfin, tenofovir alafenamide, thiamine, trandolapril, tropicamide, velpatasvir, ximelagatran, zinc picolinate, zolpidem, or a combination thereof.

30. The pharmaceutical composition of any one of claims 1-10, wherein the pharmaceutical compound has a pKa of about 6 to about 7.

31. The pharmaceutical composition of claim 30, wherein the pharmaceutical compound comprises a 1,4-benzodiazepine, 1-ribosyl-imidazolecarboxamide, 2-benzimidazolylcarbamicAttorney Docket No.: 53160-716.601 acid ester, 8-hydroxyquinoline, amine, amino acid, peptide, androstane steroid, anilide, aniline and substituted aniline, anthraquinone, aryl thioether, benzodiazine, benzoic acid, beta lactam, biphenyl, bipyridines and oligopyridine, bisphosphonate, carbonyl compound, diphenylmethane, ether, hexacarboxylic acid, imidazole, imidazoquinoline, indolequinone, naphthyridine, oxosteroid, phenethylamine, phenylbenzimidazole, phenylhydrazine, phenylpiperidine, phenylpyridine, phenylquinoline, pterin, purine ribonucleotide, purines and purine derivative, pyrazolo[1,5-a]pyrimidine, pyridine carboxaldehyde, pyridinecarboxylic acid, pyridinesulfonamide, pyridoindole, quinoline carboxylic acid, styrene, sulfinylbenzimidazole, trifluoromethylbenzene, or a derivative thereof, or a combination thereof.

32. The pharmaceutical composition of claim 30 or 31, wherein the pharmaceutical compound comprises 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, 5- methyltetrahydrofolic acid, abacavir, adefovir dipivoxil, adenine, alprazolam, ALT-2074,amdoxovir, apilimod, avanafil, azelnidipine, benazepril, benzimidazole , bicisate, biricodardicitrate, brilliant green, capravirine, carbidopa, cerivastatin, cilazapril, cisplatin, clevidipine, clonixin, clopidogrel, cocarboxylase, dapivirine, delamanid, dersalazine, dolasetron, elbasvir,enalapril, etifoxine, etozoline, famciclovir, felodipine, floctafenine, fominoben, fosaprepitant,GTS-21, hetacillin, imidacloprid, imiquimod, incadronic acid, indibulin, isosulfan blue, isradipine, kinetin, lamotrigine, ledipasvir, meclinertant, mesalazine, methenamine, moexipril, morniflumate, nevirapine, nifedipine, niflumic acid, nimodipine, nisoldipine, nitrendipine, olmesartan, pazopanib, peldesine, perindopril, phenelzine, picoplatin, pinacidil, pioglitazone, pipecuronium, pradefovir mesylate, prasugrel, prinomastat, procarbazine, pyridoxine, quinapril, ramipril, rilpivirine, rostaporfin, ruxolitinib, seliciclib, sildenafil, sonidegib, spirapril, stannsoporfin, talmapimod, taribavirin, temocapril, temoporfin, tenofovir alafenamide, thiamine, trandolapril, tropicamide, velpatasvir, ximelagatran, zinc picolinate, zolpidem, acarbose, ajmaline, alcaftadine, alfentanil, alfuzosin, almitrine, amisulpride, amoxicillin, ampicillin, amrubicin, antrafenine, aripiprazole, asenapine, atipamezole, azaperone, bacampicillin, cefaclor, cefadroxil, cefdinir, cefprozil, cephalexin, cephaloglycin, chlordiazepoxide, clozapine, dalfopristin, dasatinib, diethylpropion, domperidone, dorzolamide, doxapram, doxazosin, drotaverine, efinaconazole, eprazinone, flavoxate, flibanserin, flupirtine, imidafenacin, indinavir, ketamine, ketotifen, lapatinib, loxapine, mepivacaine, methacycline, moxonidine, nefazodone, oftasceine, olanzapine, ondansetron, phendimetrazine, pivampicillin, pramocaine, prazosin, quetiapine, ranolazine, rupatadine, setiptiline, terazosin, tetrabenazine, ticlopidine, tizanidine, tofacitinib, trazodone, trimethoprim, valaciclovir, valganciclovir, ziprasidone, or a combination thereof.Attorney Docket No.: 53160-716.601 33. The pharmaceutical composition of claim 2-9, wherein the pharmaceutical compound has a pKa of about 7 to about 8.

34. The pharmaceutical composition of claim 33, wherein the pharmaceutical compound comprises an ajmaline-sarpagine alkaloid, 1,4-benzodiazepine, 2,3,5-trisubstituted thiophene, alcohols and polyol, amine, amino acid or peptide, anilide, anisole, benzazepine, benzazocine, benzene, benzimidazole, benzocycloheptapyridine, benzodiazepine, benzodiazine, benzofuran, benzoic acid, benzothiadiazole, benzothiazepine, benzotriazole, benzoxazepine, benzoxepine, benzylamine, benzylisoquinoline, benzylpiperidine, beta lactam, biphenyl, carbazole,carbohydrate, carbonyl compound, carboxylic acid, cycloheptathiophene, diarylheptanoid ,diazanaphthalene, diazinane, diazine, dibenzocycloheptene, dibenzodiazepine, dibenzothiazepine, dibenzoxazepine, dibenzoxepine, diphenylmethane, ergolin, flavone, flavonoid, halobenzene, hybrid peptide, hydropyridine, indane, indole, indoline, isoquinoline, isoquinolone, lactam, linear diarylheptanoid, lysergic acid, macrolactam, macrolide lactam, monoterpenoid, morpholine, n-acylpiperidine, n-alkylindole, naphthacene, naphthopyranone, naphthopyran, n-phenylurea, organonitrogen compound, organooxygen compound, oxazinane, pentacarboxylic acid, peptidomimetic, phenanthrene, phenethylamine, phenol ether, phenylmethylamine, phenylpiperidine, phenyltropane, piperazine, piperidinecarboxylic acid,piperidine, polypeptide, prenol lipid, pyridazines and derivative, pyridine, pyrimidine 2'-deoxyribonucleoside, pyrimidine nucleoside, pyrimidine, quinoline carboxylic acid, quinoline, steroid ester, steroid, tetracenequinone, tetracycline, tetrahydroisoquinoline, thienopyridine, thiophene, tropane alkaloid, xylene, yohimbine alkaloid, or derivatives thereof, or a combination thereof.

35. The pharmaceutical composition of claim 33, wherein the pharmaceutical compound comprises acarbose, ajmaline, alcaftadine, alfentanil, alfuzosin, alizapride, almitrine, almorexant, altretamine, altropane, alvocidib, amdinocillin, aminolevulinic acid, amisulpride, amoxicillin, ampicillin, amrubicin, antrafenine, aripiprazole, asenapine, atipamezole, AV-412, azaperone, azatadine, bacampicillin, barnidipine, benidipine, bifeprunox, bleomycin, blonanserin, bradanicline, brifentanil, bupivacaine, buspirone, cariporide, cariprazine, casopitant, cathinone, cefaclor, cefadroxil, cefdinir, cefprozil, cefradine, cephalexin, cephaloglycin, cethromycin, cetirizine, chlorcyclizine, chlordiazepoxide, chlortetracycline, cilansetron, clozapine, dalfopristin, dapiprazole, dasatinib, deserpidine, diethylpropion, domperidone, dorzolamide, dovitinib, doxapram, doxazosin, doxycycline, drotaverine, edonerpic, efinaconazole, elsamitrucin, eluxadoline, enalaprilat, enzastaurin, eprazinone, ergonovine, ergotamine, EVT-101, ezatiostat, facinicline, fenproporex, finafloxacin, flavoxate,Attorney Docket No.: 53160-716.601 flibanserin, flunarizine, flupirtine, hexaminolevulinate, hydroxyzine, iclaprim, iloperidone, imidafenacin, indinavir, josamycin, ketamine, ketotifen, lapatinib, larazotide, lesopitron, levobupivacaine, levocetirizine, lidocaine, linaclotide, lofexidine, loracarbef, lorpiprazole, loxapine, lysergic acid diethylamide, manidipine, mepiprazole, mepivacaine, methacycline, methyl aminolevulinate, methylergometrine, methysergide, miglitol, motesanib, moxonidine, naloxone, naluzotan, nefazodone, netupitant, oftasceine, olanzapine, onalespib, ondansetron, oxytetracycline, palonosetron, perospirone, phendimetrazine, phenoxybenzamine, pirenzepine, pivampicillin, pivmecillinam, pizotifen, pramocaine, prazosin, priralfinamide, prx-08066, pyrimethamine, quetiapine, RAF-265, raloxifene, ranolazine, reboxetine, remifentanil, rescinnamine, reserpine, rifampicin, rifapentine, rocuronium, ropivacaine, rupatadine, safinamide, saxagliptin, setiptiline, SNX-5422, solithromycin, sufugolix, SUVN-502, talactoferrin alpha, telithromycin, terazosin, tetrabenazine, ticlopidine, tipifarnib, tizanidine, tofacitinib, trabectedin, trazodone, trimethoprim, trimetrexate, tymazoline, valaciclovir, valganciclovir, valomaciclovir, valtorcitabine, venetoclax, voglibose, yohimbine, ziprasidone, zosuquidar, or a combination thereof.

36. The pharmaceutical composition of claims 2, wherein the pharmaceutical compound has a pKa of about 8 to about 9.

37. The pharmaceutical composition of claim 36, wherein the pharmaceutical compound comprises a 1-benzopyran, 1-benzothiopyran, 1-phenyltetrahydroisoquinoline, alcohol, polyol, amine, amino acid, peptide, aminoquinoline and derivative, androstane steroid, anilide, anisole, aryl thioether, benzenediol, benzenesulfonamide, benzo-1,4-dioxane, benzodiazine, benzoic acid and derivative, benzoquinoline, benzylamine, benzylether, benzylpiperidine, beta lactam, biphenyl and derivative, carbazole, carbohydrate and carbohydrate conjugate, carbonyl compound, carboxylic acid derivative, depsipeptide, dibenzazepine, dibenzothiepin, dibenzoxazepine, diphenylacetonitrile, diphenylfuran, diphenylmethane, ether, fatty acid and conjugate, fentanyl, galanthamine-type amaryllidaceae alkaloid, halobenzene, hydropyridine, imidazolidine, indazole, indole, indoloquinoline, isoquinolone and derivative, isoxazoline,lysergic acid and derivative, methoxybenzene, monoterpenoid, morpholine, n -alkylindole,naphthyridine, oxadiazole, pentacarboxylic acid and derivative, phenethylamine, phenothiazine, phenoxazine, phenoxy compound, phenylmethylamine, phenylnaphthalene, phenylpiperidine, phenylpropane, phenylpyridine, phenylpyrrolidine, phenylquinoline, piperazine, piperidinecarboxylic acid and derivative, purine and purine derivative, pyrimidine and pyrimidine derivative, pyrrolidinylpyridine, quinoline carboxamide, quinoline carboxylic acid, styrene, substituted pyrrole, sulfanilide, tetracarboxylic acid and derivative, thiazole, thiopheneAttorney Docket No.: 53160-716.601 carboxylic acid and derivative, trifluoromethylbenzene, xylene, or a derivative thereof, or a combination thereof.

38. The pharmaceutical composition of claim 36 or 37, wherein the pharmaceutical compound comprises aceprometazine, acetophenazine, aclarubicin, acrivastine, afatinib, afimoxifene, alanosine, amiodarone, ammonia n-13, ammonium molybdate, amonafide, amorolfine, amoxapine, amsacrine, amylocaine, anamorelin, anileridine, aplindore, apraclonidine, articaine, arzoxifene, asimadoline, aspartame, astemizole, atrasentan, azelastine, azimilide, bedaquiline, benzylfentanyl, bosutinib, brexpiprazole, brimonidine, bromodiphenhydramine, buclizine, budiodarone, bupivacaine, bupropion, butyrfentanyl, caldaret, captodiame, carbinoxamine, carfentanil, carvedilol, cefminox, cefotiam, celgosivir, cevimeline, chlorcyclizine, chloroprocaine, chloropyramine, chlorotoxin I-131, cinnarizine, ciprofloxacin, cisapride, clarithromycin, clofedanol, clomocycline, clonidine, cloperastine, CNS- 5161, cocaine, cyclacillin, cyclizine, cyclopentolate, cycloserine, cyproheptadine, darapladib, daunorubicin, DDP-225, demeclocycline, deramciclane, desvenlafaxine, dicyclomine, dihydroergotamine, diltiazem, dimenhydrinate, dimetotiazine, diphenhydramine, diphenoxylate,diphenylpyraline, dofetilide, donepezil, dotarizine, doxorubicin, doxylamine, droxidopa, d -serine, dyclonine, edetic acid, edivoxetine, elacridar, eletriptan, eliglustat, emedastine, enoxacin, eperisone, epinastine, epinephrine, epirubicin, erythromycin, ethoheptazine, famotidine, fasudil, fentanyl, flupentixol, fluphenazine, flurazepam, forodesine, friulimicin B, gaboxadol, gadoversetamide, galantamine, garenoxacin, gatifloxacin, glesatinib, glucosamine, glypromate, granisetron, grepafloxacin, haloperidol, hydrocodone, hydromorphone, idarubicin, imatinib, imolamine, indium In-111 pentetate, iroxanadine, isoaminile, isoprenaline, isothipendyl, isoxsuprine, istaroxime, itopride, ketobemidone, lasofoxifene, l-asparagine, levobupivacaine, levonordefrin, lincomycin, lobeline, lofentanil, lomefloxacin, l-threonine, lucanthone, lumateperone, lurasidone, LY-517717, managlinat dialanetil, masitinib, meclizine, melperone, mepyramine, mequitazine, mesoridazine, methdilazine, midodrine, migalastat, miglustat, mimosine, minocycline, moxisylyte, naloxegol, nebivolol, nelfinavir, nicardipine, nicergoline, nicotine, norepinephrine, norfloxacin, normethadone, ocaperidone, ohmefentanyl, orphenadrine, osimertinib, oxybuprocaine, oxybutynin, oxycodone, oxyphencyclimine, pafuramidine, palbociclib, paliperidone, paliroden, pargyline, PBT-1033, pelitinib, pentetate calcium trisodium, pentetate zinc trisodium, pentostatin, perphenazine, pethidine, p-fluorofentanyl, phenindamine, phenmetrazine, phenyltoloxamine, pimavanserin, pimozide, pipamperone, pipazethate, pipendoxifene, pipotiazine, pirlindole, ponatinib, PPI-1019, prilocaine, procaine, prochlorperazine, proflavine, proparacaine, propericiazine, propiomazine, propoxycaine,Attorney Docket No.: 53160-716.601 protokylol, prucalopride, PRX-07034, quinagolide, quinupristin, rabeximod, ranitidine, rasagiline, remacemide, remoxipride, renzapride, rifabutin, rifalazil, rilapladib, risperidone, rivastigmine, robalzotan, rolapitant, rolitetracycline, roxatidine acetate, saquinavir, sarafloxacin, sarizotan, selegiline, serine, sertindole, sincalide, sitagliptin, solifenacin, sparfloxacin, spinosad, sufentanil, sulpiride, tacrine, talabostat, tamoxifen, tariquidar, technetium tc-99m tetrofosmin, tegaserod, terbinafine, terconazole, tetracaine, tetracycline, tetrofosmin, thienylfentanyl, thioproperazine, thioridazine, thiothixene, thonzylamine, tianeptine, tigecycline, tocainide, tolperisone, toremifene, trifluoperazine, trimebutine, trimethobenzamide, tripelennamine, triprolidine, tromethamine, tubocurarine, udenafil, vanoxerine, veliparib, venlafaxine, vicriviroc, vilazodone, viloxazine, vinblastine, vincristine, vindesine, vinorelbine, voacamine, vortioxetine, xaliproden, xanthinol, zanapezil, zotepine, zuclopenthixol, α-methylfentanyl, α- methylthiofentanyl, β-hydroxythiofentanyl, or a combination thereof.

39. The pharmaceutical composition of any one of claims 2-4, wherein the pharmaceutical compound has a pKa of about 9 to about 10.

40. The pharmaceutical composition of claim 39, wherein the pharmaceutical compound comprises a 1-benzopyran, 1-benzothiopyran, 1-hydroxy-4-unsubstituted benzenoid, 4- quinolinemethanol, 5’-deoxy-5’-thionucleoside, amine, amino acid, peptide, aminophenyl ether,aminoquinoline, anilide, anisole, anthraquinone, benzenediol, benzenesulfonamide, benzo -1,4-dioxane, benzodiazine, benzoic acid, benzonitrile, benzoquinoline, benzoxazinone, benzoyl, benzyl alcohol, benzylether, benzylpiperidine, beta lactam, biphenyl, bisphosphonate, carbazole, carbohydrate and carbohydrate conjugate, cytisine, depsipeptide, dibenzazepine, dibenzothiepin, dibenzoxepine, dicarboxylic acid, diphenylacetonitrile, diphenylmethane, diterpenoid, ether, fentanyl, glycerophosphoserine, halobenzene, hybrid peptide, hydropyridine, hydroquinoline, hydroxypyridine, indazole, indolecarboxylic acid, indole, indoline, indoloquinoline, indolyl carboxylic acid, isoquinoline quinone, lysergic acid, methoxybenzene, naphthyridine, nitrobenzene, nitroquinoline, organosulfonic acid, pentacarboxylic acid, phenethylamine, pheniramine, phenothiazine, phenoxazine, phenoxy compound, phenoxyacetic acid, phenylacetamide, phenylbutylamine, phenylmethylamine, phenylpiperidine, phenylpropane, phenyltropane, piperazine, piperidinecarboxylic acid, pregnane steroid, purines and purine, pyridinium, quinoline carboxylic acid, quinolone, steroid ester, styrene, substituted pyrrole, sulfanilide, tametraline, thiophene carboxylic acid, toluene, trifluoromethylbenzene, tryptamine,tyrosol, or a derivative thereof, or a combination thereof .

41. The pharmaceutical composition of claim 39 or 40, wherein the pharmaceutical compound comprises (3S)-3-methyl-D-aspartic acid, isoxsuprine, 13-deoxydoxorubicin, 3-Attorney Docket No.: 53160-716.601 allylfentanyl, 3-methylfentanyl, 4-phenylfentanyl, 7-hydroxystaurosporine, acebutolol, ademetionine, aldoxorubicin, alendronic acid, alethine, alimemazine, aliskiren, almotriptan, alogliptin, alprenolol, ambroxol, amibegron, amikacin, amineptine, aminocandin, amitriptyline, amlodipine, amphotericin b, antazoline, apramycin, aprindine, arbaclofen, arbekacin, arbutamine, arformoterol, arimoclomol, arotinolol, arylacenamide, atenolol, atomoxetine, atosiban, atropine, azithromycin, bacitracin, baclofen, bambuterol, bazedoxifene, becatecarin, benfluorex, benzatropine, benzphetamine, benzydamine, benzylpenicilloyl polylysine, bepotastine, bepridil, besifloxacin, betahistine, betaxolol, betazole, bevantolol, bilastine, bimoclomol, biperiden, bisoprolol, bopindolol, brasofensine, bromhexine, bromopride, brompheniramine, bufuralol, bupranolol, butenafine, cabergoline, canfosfamide, carbocisteine, carteolol, caspofungin, cediranib, ceforanide, ceftolozane, celiprolol, chlorphenamine, chlorpromazine, chlorprothixene, cilastatin, cinchocaine, cinitapride, citalopram, clemastine, clenbuterol, clocapramine, clofazimine, clomifene, clomipramine, cobimetinib, codeine, colestipol, CP-122721, cyamemazine, cyclobenzaprine, cycrimine, cystine, cytisine, dalbavancin, dapoxetine, daptomycin, darinaparsin, declopramide, demexiptiline, desloratadine, dexbrompheniramine, dexchlorpheniramine maleate, dexmethylphenidate, dextromethorphan,dextropropoxyphene, dextrothyroxine, dezocine, difenoxin, dihydrocodeine, dim etacrine,dimetindene, diphenidol, dipivefrin, diprenorphine, dirithromycin, D-methionine, dobutamine, dopamine, doripenem, dosulepin, doxepin, dronedarone, duloxetine, encainide, enclomiphene, ephedrine, epicept NP-1, eribulin, ertapenem, escitalopram, esmolol, ethambutol, ethopropazine, ethylmorphine, etidocaine, etryptamine, fenoterol, fenspiride, ferrous bisglycinate, fexofenadine, filanesib, fingolimod, flecainide, fluoxetine, fluspirilene, fluvoxamine, formoterol, framycetin, gabapentin, gadobenic acid, gadofosveset trisodium, gadopentetate dimeglumine, gadoteridol, gadoxetic acid, gemifloxacin, glutamic acid, glutathione, glutathione disulfide, glycine, golotimod, gosogliptin, granisetron, halofuginone, heroin, hexetidine, hexylcaine, histamine, histidine, homatropine, huperzine A, huperzine B, hydroxyamphetamine, hydroxychloroquine, hyoscyamine, ibandronate, ifenprodil, imipramine, indacaterol, ioflupane I-123, irinotecan, isoetarine, ispinesib, ivabradine, K201, kanamycin, labetalol, L-alanine, L-aspartic acid, L- citrulline, L-cysteine, lercanidipine, leukotriene C4, levallorphan, levamlodipine, levobetaxolol, levobunolol, levodopa, levomethadyl acetate, levomilnacipran, levorphanol, levothyroxine, L- glutamine, linagliptin, liothyronine, liotrix, L-isoleucine, LJP 1082, L-leucine, lomitapide, loperamide, L-phenylalanine, L-threonine, L-tryptophan, L-tyrosine, lumefantrine, L-valine, lymecycline, mafenide, magnesium glycinate, mefloquine, melphalan, meropenem, metaraminol, methadone, methadyl acetate, methionine, methotrimeprazine, methoxamine,Attorney Docket No.: 53160-716.601 methyldopa, methylphenidate, metipranolol, metixene, metoclopramide, metoprolol, metyrosine, mexiletine, mibefradil, milnacipran, mirabegron, mitemcinal, mitoxantrone, mn-305, morphine, moxifloxacin, nadolol, naftifine, nalmefene, naratriptan, naronapride, natamycin, nemonoxacin, netilmicin, nitroarginine, NPS-2143, NS-2359, nystatin, oglufanide, olodaterol, olopatadine, omacetaxine mepesuccinate, OPC-28326, orciprenaline, osanetant, oseltamivir, oxamniquine, oxilofrine, oxitriptan, oxprenolol, pamidronate, paromomycin, paroxetine, penbutolol, penicillamine, pentoxyverine, pergolide, phenaridine, phenindamine, pheniramine, phentolamine, phenylephrine, phenylpropanolamine, pholcodine, phosphatidyl serine, piboserod, pindolol, piperazine, pirarubicin, pirbuterol, pixantrone, polaprezinc, pracinostat, practolol, procainamide, procaterol, procyclidine, promazine, promethazine, propafenone, propoxyphene napsylate, propranolol, PRX-03140, pseudoephedrine, PX-478, quarfloxin, quinidine, quinidine barbiturate, quinine, repinotan, retapamulin, ribostamycin, ritodrine, rizatriptan, ronacaleret, roxithromycin, salbutamol, salmeterol, saredutant, selenomethionine, seproxetine, serotonin, sertraline, sibutramine, silodosin, siramesine, solabegron, sotalol, spectinomycin, spiramycin, sumanirole, sumatriptan, sunitinib, tamsulosin, tandutinib, tapentadol, TAS-108, taurine, tedisamil, telavancin, terbutaline, terfenadine, tesmilifene, tesofensine, tetrodotoxin, TG-100801, tiagabine, ticalopride, tilmicosin, timolol, tobramycin, topotecan, tramadol, tranylcypromine, triethylenetetramine, triflupromazine, trihexyphenidyl, trimetazidine, trimipramine, trovafloxacin, tyramine, ubenimex, vancomycin, vandetanib, varenicline, vecuronium, verapamil, vernakalant, vigabatrin, vilanterol, vildagliptin, zolmitriptan, α-methylacetylfentanyl, α-methylfentanyl, β-methylfentanyl, or a combination thereof.

42. The pharmaceutical composition of any one of claims 2-4, wherein the pharmaceutical compound has a pKa of about 10 to about 13.

43. The pharmaceutical composition of claim 42, wherein the pharmaceutical compound comprises 2,6-dimethyl-3-benzazocine, alkaline earth metal oxide, alkylthiol, amine, amino acid, peptide, aminopyridine, aminoquinoline, benzenediol, benzoic acid, benzoquinoline, beta lactam, bile acid, alcohol, biphenyl, bisphosphonate, carbazole, carbohydrates and carbohydrate conjugate, carboxylic acid derivative, cyclohexylamine, depsipeptide, dibenzazepine, diphenylmethane, ether, fatty acids and conjugate, guanidine, halobenzene, hybrid peptide, indolecarboxylic acid, indole, indoline, monoterpenoid, n-arylamide, organosulfonic acid, peptoid-peptide hybrid, phenethylamine, pheniramine, phenylbutylamine, phenylmethylamine, phenylpiperidine, phenylpropane, phenylpropylamine, phenylpyridine, piperidinecarboxylicAttorney Docket No.: 53160-716.601 acid, purines and purine derivative, pyrazolylpyridine, pyrimidines and pyrimidine derivative, tetracarboxylic acid, tryptamine, urea, xylene, or a derivative thereof, or a combination thereof.

44. The pharmaceutical composition of claim 42 or 43, wherein the pharmaceutical compound comprises 2-iminobiotin, abarelix, ABT-510, afamelanotide, agmatine, alverine, alvimopan, amantadine, AMD-070, amifostine, aminocaproic acid, amodiaquine, amphetamine, anatibant, apomorphine, argatroban, arverapamil, atiprimod, aviptadil, bedoradrine, benzoctamine, bethanidine, bicifadine, bivalirudin, brostallicin, buformin, buprenorphine, butorphanol, butriptyline, capreomycin, carbamide peroxide, ceftobiprole, ceritinib, cetrorelix, chlorhexidine, chloroquine, chlorphentermine, cinacalcet, corticorelin ovine triflutate, cr665, creatine, crizotinib, cysteamine, CZEN 002, dalfampridine, darifenacin, debrisoquin, deferoxamine, degarelix, delcasertib, denibulin, desipramine, deslorelin, desmopressin, dexfenfluramine, dextroamphetamine, diethylnorspermine, dihydrostreptomycin, disopyramide,eflornithine, enviomycin, etorphine, felypressin, fencamfamine, fenethylline, fenfluramin e,fenoldopam, fesoterodine, fradafiban, frovatriptan, fursultiamine, gadoteric acid, gadoteridol, gamma-aminobutyric acid, ganirelix, gentamicin, gonadorelin, goserelin, guanadrel, guanethidine, guanidine, halofantrine, hexoprenaline, histrelin, hydroxyproline, hydroxystilbamidine isethionate, ibutilide, icatibant, imipenem, indalpine, indecainide, iobenguane, iobenguane sulfate I-123, isometheptene, labradimil, L-aminocarnityl-succinyl- leucyl-argininal-diethylacetal, lanreotide, L-arginine, L-eflornithine, levmetamfetamine, levocabastine, lisdexamfetamine, lisinopril, lixisenatide, L-lysine, lorcaserin, L-proline, magnesium oxide, maprotiline, maraviroc, mecamylamine, memantine, mephentermine, metformin, methamphetamine, midomafetamine, nafarelin, nalbuphine, naltrexone, naphazoline, neramexane, neridronic acid, nintedanib, nor-noha, nortriptyline, nylidrin, obinepitide, octreotide, olcegepant, oritavancin, ornithine, otamixaban, oxymetazoline, oxymorphone, panobinostat, pasireotide, pemetrexed, pentamidine, pentazocine, peramivir, perhexiline, phencyclidine, phenformin, phentermine, pimagedine, piracetam, plerixafor, polymyxin B sulfate, pozanicline, pramipexole, pregabalin, prezatide, primaquine, progabide, proguanil, propylhexedrine, protriptyline, pyrantel, quinacrine, ramoplanin, rifaximin, rimantadine, rivanicline, romidepsin, ropinirole, rotigotine, saralasin, satraplatin, serotonin, SGS-742, sitamaquine, SNS-032, somatostatin, spermine, SQ-109, squalamine, streptomycin, T131, tafenoquine, talotrexin, tanespimycin, tecastemizole, tenocyclidine, terlipressin, tesamorelin, tetracosactide, tetryzoline, tezampanel, tipiracil, tirofiban, tolazoline, tolterodine, tramiprosate, tranexamic acid, triptorelin, ularitide, urea C-13, vapitadine, vintafolide, viomycin, WX-UK1, xylometazoline, zanamivir, or a combination thereof.Attorney Docket No.: 53160-716.601 45. The pharmaceutical composition of any one of claims 1-44, wherein the pharmaceutical composition is a solid.

46. The pharmaceutical composition of claim 45, wherein the pharmaceutical compound has a pKa of at least 2.

47. The pharmaceutical composition of claim 45, wherein the pharmaceutical compound has a pKa of about 2 to about 7.

5.

48. The pharmaceutical composition of claim 45, wherein the pharmaceutical compound has a pKa of about 1 to about 5.

49. The pharmaceutical composition of claim 45, wherein the pharmaceutical compound has a pKa of about 7.5 to about 11.

50. The pharmaceutical composition of any one of claims 1-44, wherein the pharmaceutical composition is formulated as a liquid.

51. The pharmaceutical composition of claim 50, wherein the pharmaceutical compound has a pKa of at least 5.

52. The pharmaceutical composition of claim 50, wherein the pharmaceutical compound has a pKa of about 5 to about 7.

53. The pharmaceutical composition of any one of claims 1-52, wherein the pharmaceutical composition when formulated as a solution has a lower osmolality than a solution comprising the composition comprising a salt of the pharmaceutical compound and a salt of the complexing agent.

54. The pharmaceutical composition of any one of claims 1-53, wherein the pharmaceutical composition improves a solubility of the pharmaceutical compound by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or about 100% as compared to a composition (i) without the complexing agent or (ii) wherein the pharmaceutical compound does not complex with one of more of the acidic functional groups of the complexing agent.

55. The pharmaceutical composition of any one of claims 1-54, wherein the pharmaceutical composition improves a solubility of the pharmaceutical compound by about 2-fold, about 3- fold, about 4-fold, about 5-fold, about 6-fold, about 7-fold, about 8-fold, about 9-fold, about 10- fold, about 20-fold, about 30-fold, about 40-fold, or about 50-fold as compared to a composition (i) without the complexing agent or (ii) wherein the pharmaceutical compound does not complex with one of more of the acidic functional groups of the complexing agent.

56. The pharmaceutical composition of any one of claims 1-55, wherein the complexing agent comprises a substituted cyclodextrin.Attorney Docket No.: 53160-716.601 57. The pharmaceutical composition of claim 56, wherein the complexing agent comprises a cyclodextrin substituted with at least one acidic functional group.

58. The pharmaceutical composition of claim 57, wherein the cyclodextrin is substituted with 3 to 8 acidic functional groups.

59. The pharmaceutical composition of claim 53, wherein the cyclodextrin is sulfobutylether-β-cyclodextrin (SBEBCD).

60. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition when formulated as a solution has a lower osmolality than a solution comprising a composition comprising a salt of the pharmaceutical compound and a salt of the complexing agent.

61. The pharmaceutical composition of claim 1, wherein the pharmaceutical is formulated for subcutaneous, intramuscular, sublingual, oral, rectal, transvaginal, or intranasal administration.

62. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition when formulated as a solution has an osmolality of no more than about 850 mOsm / kg.

63. The pharmaceutical composition of claim 62, wherein the pharmaceutical composition has a pH of about 4 to about 7.

64. The pharmaceutical composition of claim 1, wherein the complexing agent is present in an amount of about 10 mg / mL to about 600 mg / mL.

65. The pharmaceutical composition of claim 1, wherein the complexing agent acts as the counterion to between 1 to 10 molecules of the pharmaceutical compound.

66. The pharmaceutical composition of claim 1, wherein the complexing agent further comprises a non-polar pore.

67. The pharmaceutical composition of claim 66, wherein the pharmaceutical composition further comprises an additional molar equivalent of the pharmaceutical compound, wherein the additional molar equivalent of the pharmaceutical compound is unionized and complexed to the non-polar pore.

68. The pharmaceutical composition of claim 1, wherein the ratio of complexing agent to the pharmaceutical compound is about 1:1.

1.

69. The pharmaceutical composition of claim 1, wherein the ratio of complexing agent to the pharmaceutical compound is about 1:

2.

70. The pharmaceutical composition of claim 1, wherein the ratio of complexing agent to the pharmaceutical compound is about 1:

3.

71. The pharmaceutical composition of claim 1, wherein the ratio of complexing agent to the pharmaceutical compound is about 1:4.Attorney Docket No.: 53160-716.601 72. The pharmaceutical composition of claim 1, wherein the ratio of complexing agent to the pharmaceutical compound is about 1:

5.

73. The pharmaceutical composition of claim 1, wherein the ratio of complexing agent to the pharmaceutical compound is about 1:6.

5.

74. The pharmaceutical composition of claim 1, wherein the pharmaceutical compound has a solubility of less than about 50 mg / ml as salt in an aqueous medium.

75. The pharmaceutical composition of claim 1, wherein the pharmaceutical compound has a solubility of less than about 10 mg / ml as salt in an aqueous medium.

76. The pharmaceutical composition of claim 1, wherein the pharmaceutical compound has a solubility of less than about 5 mg / ml as salt in an aqueous medium.

77. The pharmaceutical composition of claim 1, wherein the pharmaceutical compound has a solubility of less than about 0.5 mg / ml as salt in an aqueous medium.

78. The pharmaceutical composition of claim 1, wherein the pharmaceutical compound has a solubility of less than about 0.1 mg / ml as salt in an aqueous medium.

79. The pharmaceutical composition of any one of claims 74-78, wherein the pharmaceutical compound is ionized.

80. The pharmaceutical composition of claim 1, wherein the pharmaceutical compound comprises rotigotine, eletriptan, DXM, midazolam, remdesivir, copanlisib, melevodopa, tigecycline, naloxone, amikacin, 1-amantadine, 2-amantadine, rimantadine, amifampridine, rapamycin, clonidine, morphine, hydrocodone, sumatriptan, ropivacaine, bupivacaine, diphenhydramine, granistetron, deschloroketamine, 2-fluoro-deschloroketamine, or caspofungin.

81. The pharmaceutical composition of any one of claims 1-80, wherein the pharmaceutical compound comprises a GABA-ergic.

82. The pharmaceutical composition of claim 81, wherein the GABA-ergic comprises Baclofen, Gaboxidol, or Muscimol, or a combination thereof.

83. The pharmaceutical composition of any one of claims 1-80, wherein the pharmaceutical compound comprises an alpha-2 agonist.

84. The pharmaceutical composition of claim 83, wherein the alpha-2 agonist comprises Clonidine, Guanfacine, or Tizanidine, or a combination thereof.

85. The pharmaceutical composition of any one of claims 1-80, wherein the pharmaceutical compound is an ophthalmic.

86. The pharmaceutical composition of claim 85, wherein the ophthalmic comprises aceclidine, atropine, azelastine, brimonidine, cyclopentolate, ketotifen, levobunolol, olopatadine, pilocarpine, proparacaine, tetracaine, timolol, or tropicamide.Attorney Docket No.: 53160-716.601 87. The pharmaceutical composition of any one of claims 1-80, wherein the pharmaceutical compound is a bisphosphonate.

88. The pharmaceutical composition of claim 87, wherein the bisphosphonate is alendronate, ibandronate, pamidronate, risedronate, or zoledronic acid, or a combination or two or more thereof.

89. The pharmaceutical composition of any one of claims 1-80, wherein the pharmaceutical compound is an antibiotic.

90. The pharmaceutical composition of claim 89, wherein the antibiotic comprises amikacin, amoxicillin, ampicillin, azithromycin, aztreonam, cefaclor, cefadroxil, cefalexin, cefazolin, cefdinir, cefditoren, cefepime, cefiderocol, cefixime, cefmetazole, cefoperazone, cefotaxime, cefotetan, cefovecin, cefoxitin, cefpodoxime, cefprozil, ceftaroline, ceftazidime, ceftibuten, ceftizoxime, ceftolozane, ceftriaxone, cefuroxime, cephalexin, cephalothin, cephapirin, cephradine, ciprofloxacin, clarithromycin, clindamycin, colistin, dalbavancin, dalfopristin, daptomycin, doripenem, doxycycline, ertapenem, eravacycline, erythromycin, fosfomycin, gentamicin, imipenem, kanamycin, lefamulin, levofloxacin, linezolid, lincomycin, meropenem, metronidazole, minocycline, moxifloxacin, nalidixic acid, neomycin, nitrofurantoin, oritavancin, penicillin, piperacillin, polymyxin B, quinupristin, retapamulin, rifampicin, streptomycin, sulfacetamide, sulfadiazine, sulfamethizole, sulfamethoxazole, sulfasalazine, sulfisoxazole, teicoplanin, telavancin, tetracycline, tigecycline, tobramycin, trimethoprim, or vancomycin, or a combination thereof.

91. The pharmaceutical composition of any one of claims 1-80, wherein the pharmaceutical compound is an anticoagulant or a thrombolytic.

92. The pharmaceutical composition of claim 91, wherein the anticoagulant or thrombolytic comprises alteplase, argatroban, bivalirudin, fondaparinux, lepirudin, streptokinase, or urokinase, or a combination or two or more thereof.

93. The pharmaceutical composition of any one of claims 1-80, wherein the pharmaceutical compound is an antifungal.

94. The pharmaceutical composition of claim 93, wherein the antifungal comprises an azole antifungal.

95. The pharmaceutical composition of claim 93, wherein the antifungal comprises albendazole, clotrimazole, econazole, fluconazole, isavuconazole, itraconazole, ketoconazole, miconazole, posaconazole, tebuconazole, thiabendazole, or voriconazole, or a combination or two or more thereof.Attorney Docket No.: 53160-716.601 96. The pharmaceutical composition of claim 93, wherein the antifungal is amphotericin B, anidulafungin, caspofungin, flucytosine, micafungin, natamycin, or voriconazole, or a combination or two or more thereof.

97. The pharmaceutical composition of any one of claims 1-80, wherein the pharmaceutical compound is an antineoplastic.

98. The pharmaceutical composition of claim 97, wherein the antineoplastic is afatinib, alectinib, alisertib, axitinib, bosutinib, cabozantinib, canertinib, carfilzomib, cediranib, ceritinib, cimicoxib, cobimetinib, dabrafenib, darapladib, dasatinib, delcasertib, dovitinib, erlotinib, etoricoxib, filanesib, glesatinib, ibrutinib, idelalisib, imatinib, ispinesib, ixazomib, lapatinib, lenvatinib, linsitinib, lonafarnib, masitinib, motesanib, nilotinib, nintedanib, odanacatib, olaparib, onalespib, osimertinib, palbociclib, pazopanib, pelitinib, ponatinib, regorafenib,rilapladib, ruxolitinib, seliciclib, sonidegib, sorafenib, sunitinib, tandutinib , tipifarnib,tofacitinib, vandetanib, varlitinib, varlitinib, vatalanib, veliparib, vemurafenib, vismodegib, or acombination or two or more thereof .

99. The pharmaceutical composition of any one of claims 1-80, wherein the pharmaceutical compound is an antiviral.

100. The pharmaceutical composition of claim 99, wherein the antiviral comprises abacavir, acyclovir, adefovir, amantadine, amprenavir, atazanavir, bictegravir, cidofovir, darunavir, dasabuvir, delavirdine, didanosine, dolutegravir, efavirenz, elvitegravir, emtricitabine, enfuvirtide, entecavir, famciclovir, foscarnet, ganciclovir, grazoprevir, imiquimod, indinavir, lamivudine, laninamivir, ledipasvir, lopinavir, maraviroc, nelfinavir, nevirapine, ombitasvir, oseltamivir, paritaprevir, penciclovir, peramivir, plerixafor, podofilox, raltegravir, ribavirin, rilpivirine, ritonavir, saquinavir, sofosbuvir, stavudine, tenofovir, tipranavir, trifluridine, valaciclovir, valganciclovir, zanamivir, or zidovudine, or a combination thereof.

101. The pharmaceutical composition of any one of claims 1-80, wherein the pharmaceutical compound comprises a cardiovascular medication.

102. The pharmaceutical composition of claim 101, wherein the cardiovascular medication comprises Bretylium, Dobutamine, Dopexamine, Epoprostenol, Esmolol, Iloprost, Nesiritide,Nitroglycerin, Norepinephrine, or Phenylephrine, or a combination or two or more thereof .

103. The pharmaceutical composition of any one of claims 1-80, wherein the pharmaceutical compound comprises a central nervous system depressant.

104. The pharmaceutical composition of claim 103, wherein the central nervous system depressant comprises alprazolam, chlordiazepoxide, clonazepam, diazepam, dexmedetomidine,Attorney Docket No.: 53160-716.601 dextromethorphan, flurazepam, gabapentin, ketamine, lorazepam, midazolam, oxazepam,propofol, temazepam, or triazolam, or a combination or two or more thereof.

105. The pharmaceutical composition of any one of claims 1-80, wherein the pharmaceutical compound comprises a central nervous system stimulant.

106. The pharmaceutical composition of claim 105, wherein the central nervous system stimulant comprises amphetamine, cocaine, dexmethylphenidate, dextroamphetamine, ephedrine, lisdexamfetamine, methamphetamine, methylphenidate, modafinil, phenylephrine,pseudoephedrine, or sibutramine, or a combination or two or more thereof.

107. The pharmaceutical composition of any one of claims 1-80, wherein the pharmaceutical compound comprises a local anesthetic.

108. The pharmaceutical composition of claim 107, wherein the local anesthetic comprises articaine, benzocaine, bupivacaine, chloroprocaine, cocaine, dibucaine, etidocaine, levobupivacaine, lidocaine, mepivacaine, prilocaine, procaine, proparacaine, ropivacaine, or tetracaine, or a combination thereof.

109. The pharmaceutical composition of any one of claims 1-80, wherein the pharmaceutical compound comprises an anti-nausea medicine.

110. The pharmaceutical composition of claim 109, wherein the anti-nausea medicine comprises dolasetron, granisetron, ondansetron, or palonosetron, or a combination thereof.

111. The pharmaceutical composition of any one of claims 1-80, wherein the pharmaceutical compound is an anti-migraine.

112. The pharmaceutical composition of claim 111, wherein the anti-migraine comprises almotriptan, avitriptan, donitriptan, eletriptan, frovatriptan, lasmiditan, naratriptan, rizatriptan, sumatriptan, or zolmitriptan, or a combination thereof.

113. The pharmaceutical composition of any one of claims 1-80, wherein the pharmaceutical compound comprises an anti-Parkinson’s medicine.

114. The pharmaceutical composition of claim 113, wherein the anti-Parkinson’s medicine comprises amantadine, apomorphine, benztropine, benserazide, bromocriptine, cabergoline, carbidopa, entacapone, foscarbidopa, foslevodopa, levodopa, melvodopa, pramipexole, rasagiline, ropinirole, rotigotine, safinamide, selegiline, tolcapone, or trihexyphenidyl, or a combination thereof.

115. The pharmaceutical composition of any one of claims 1-80, wherein the pharmaceutical compound comprises an antihistamine.

116. The pharmaceutical composition of claim 115, wherein the antihistamine comprises acrivastine, brompheniramine, cetirizine, chlorpheniramine, clemastine, cyproheptadine,Attorney Docket No.: 53160-716.601 desloratadine, dexchlorpheniramine, diphenhydramine, doxylamine, fexofenadine, hydroxyzine, levocetirizine, loratadine, meclizine, promethazine, or tripelennamine, or a combination thereof.

117. The pharmaceutical composition of any one of claims 1-80, wherein the pharmaceutical compound comprises an H2 histamine receptor blocker.

118. The pharmaceutical composition of claim 117, wherein the H2 histamine receptor blocker is cimetidine, famotidine, nizatidine, or ranitidine, or a combination thereof.

119. The pharmaceutical composition of any one of claims 1-80, wherein the pharmaceutical compound comprises an opioid.

120. The pharmaceutical composition of claim 119, wherein the opioid comprises buprenorphine, butorphanol, codeine, fentanyl, heroin, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, naloxone, naltrexone, nalmefene, oxycodone, oxymorphone, pentazocine, sufentanil, tapentadol, or tramadol, or a combination or two or more thereof.

121. The pharmaceutical composition of any one of claims 1-80, wherein the pharmaceutical compound is a tyrosine kinase inhibitor.

122. The pharmaceutical composition of claim 121, wherein the tyrosine kinase inhibitor comprises bosutinib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, ponatinib, sorafenib, or sunitinib or two or more thereof.

123. The pharmaceutical composition of any one of claims 1-80, wherein the pharmaceutical compound comprises amifampridine, amifostine, aminocaproic acid, argatroban, asenapine, atropine, bivalirudin, cisatracurium, deferoxamine, desmopressin, gabapentin, lurasidone, milrinone, nicotine, octreotide, pregabalin, rocuronium, terbutaline, tirofiban, tranexamic acid, vecuronium, nepafenac, or any combination thereof.

124. A pharmaceutically acceptable salt of a compound pharmaceutical comprising: (i) a pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the pharmaceutical compound comprises a protonated nitrogen atom and a pKa of about 1 to about 7; and (ii) a conjugate base of a complexing agent comprising a plurality of acidic functional groups, wherein at least one acidic functional group of the plurality of acidic functional groups acts as a counterion of the pharmaceutical compound, wherein the molar ratio of the conjugatebase of the complexing agent to the pharmaceutical compound is from about 1:1 to about 1:10.

125. A pharmaceutically acceptable salt of a compound pharmaceutical comprising:Attorney Docket No.: 53160-716.601 (i) a pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein thepharmaceutical compound comprises a protonated nitrogen atom and a pKa of at least 1; and(ii) a conjugate base of a complexing agent comprising a plurality of acidic functional groups, wherein at least one acidic functional group of the plurality of acidic functional groups acts as a counterion of the pharmaceutical compound, wherein the molar ratio of the conjugate base of thecomplexing agent to the pharmaceutical compound is from about 1:1 to about 1:10.

126. A pharmaceutically acceptable salt of a compound pharmaceutical comprising: (i) a pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the pharmaceutical compound comprises a protonated nitrogen atom and a pKa of about 1 to about 13; and (ii) a conjugate base of a complexing agent comprising a plurality of acidic functional groups, wherein at least one acidic functional group of the plurality of acidic functional groups acts as a counterion of the pharmaceutical compound, wherein the molar ratio of the conjugate base of thecomplexing agent to the pharmaceutical compound is from about 1:1 to about 1:10.

127. A pharmaceutically acceptable salt of a compound pharmaceutical comprising: (i) a pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the pharmaceutical compound comprises a protonated nitrogen atom and a pKa of about 4 to about 13; and (ii) a conjugate base of a complexing agent comprising a plurality of acidic functional groups, wherein at least one acidic functional group of the plurality of acidic functional groups acts as a counterion of the pharmaceutical compound, wherein the molar ratio of the conjugate base of the complexing agent to the pharmaceutical compound is from about 1:1 to about 1:

10.

128. The pharmaceutically acceptable salt of any one of claims 124-127, wherein the complexing agent comprises a substituted cyclodextrin.

129. The pharmaceutically acceptable salt of any one of claims 124-128, wherein thecomplexing agent comprises a cyclodextrin substituted with at least one acidic functional group.

130. The pharmaceutically acceptable salt of any one of claims 124-129, wherein the cyclodextrin is substituted with 3 to 8 acidic functional groups.

131. The pharmaceutically acceptable salt of any one of claims 124-130, wherein the cyclodextrin is sulfobutylether-β-cyclodextrin (SBEBCD).Attorney Docket No.: 53160-716.601 132. The pharmaceutically acceptable salt of any one of claims 124-131, wherein the pharmaceutical compound has a pKa of at least 1.

133. The pharmaceutically acceptable salt of any one of claims 124-132, wherein thepharmaceutical compound has a pKa of about 1 to about 7.5.

134. The pharmaceutically acceptable salt of any one of claims 124-133, wherein the pharmaceutical compound has a pKa of about 1 to about 5.

135. The pharmaceutically acceptable salt of any one of claims 124-134, wherein thepharmaceutical compound has a pKa of about 7.5 to about 13.

136. The pharmaceutically acceptable salt of any one of claims 124-135, wherein the pharmaceutical compound comprises 5'-deoxyribonucleosides, 6,7-benzomorphans, ajmaline- sarpagine alkaloids, alkaline earth metal organides, amaryllidaceae alkaloids, anthracenes, anthracyclines, aporphines, azaspirodecane, azepanes, azobenzenes, azoles, azolidines, azolines, benzazepines, benzene and substituted, benzimidazole ribonucleosides and ribonucleotides, benzimidazoles, benzocycloheptapyridines, benzodiazepines, benzodioxanes, benzodioxoles, benzofurans, benzopyrans, benzopyrazoles, benzothiadiazoles, benzothiazepines, benzothiazines, benzothiazoles, benzothiepins, benzothiophenes, benzothiopyrans,benzotriazoles, benzoxadiazoles, benzoxazepines, benzoxazines, benzoxepines, biotin ,camptothecins, carboxylic acids, cephalotaxus alkaloids, cinchona alkaloids, cinnamic acids, coumarans, cycloheptathiophenes, depsides and depsidones, diarylheptanoids,diazanaphthalenes, diazinanes, diazines, dibenzocycloheptenes, dioxanes, epoxides, ergoline ,fatty acyls, flavin nucleotides, flavonoids, fluorenes, furans, furopyrans, glycerophospholipids, homogeneous other non-metal compounds, hydroxy acids, ibogan-type alkaloids, imidazodiazepines, imidazole ribonucleosides and ribonucleotides, imidazopyridines, imidazopyrimidines, imidazothiazoles, indanes, indenes and isoindenes, indoles, indolizidines, isocoumarans, isoindoles, isoquinolines, lactams, linear 1,3-diarylpropanoids, lupin alkaloids, macrolactams, macrolide lactams, macrolides morphinans, naphthacenes, naphthalenes,naphthofurans, naphthopyrans, nucleoside and nucleotide analogues , organic carbonic acids,organic phosphines, organic phosphonic acids, organic sulfonic acids, organonitrogen compounds, organooxygen compounds, organothiophosphorus compounds, oxazinanes, peptidomimetics, phenanthrenes, phenanthrolines, phenol esters, phenol ethers, phenols, phenylpropanoic acids, phthalide isoquinolines, piperazinoazepines, piperidines, polypeptides, prenol lipids, pteridines, purine nucleosides, purine nucleotides, pyrazolopyridines, pyrazolopyrimidines, pyridines, pyridopyrimidines, pyrimidine nucleosides, pyrroles,pyrrolidines, pyrrolopyrazines, pyrrolopyridines, pyrrolopyrimidines, quinolines , steroids andAttorney Docket No.: 53160-716.601 steroid, stilbenes, tetracyclines, tetrahydroisoquinolines, tetralins, thiadiazines, thienodiazepines, thienopyridines, thienothiazines, thiochromenes, thioethers, thiols, thiophenes, transition metal salts, triazinanes, triazines, triazole ribonucleosides and ribonucleotides, triazolopyrimidines,triphenyl compounds, tropane alkaloids, vinca alkaloids, yohimbine alkaloids, or a der ivativethereof, or a combination thereof.

137. The pharmaceutically acceptable salt of any one of claims 124-134, wherein thepharmaceutical compound has a pKa of about 1 to about 2.

138. The pharmaceutically acceptable salt of claim 137, wherein the pharmaceutical compound comprises a 1,4-benzodiazepine, amine, amino acid, peptide, androstane steroid, benzenesulfonamide, benzoic acids, benzophenone, benzothiadiazine, biphenyls, carboxylic acid derivative, depsipeptide, diphenylmethane, ether, halobenzene, isoindoline, nitrogen mustard compound, nitroquinolines, purine 2’-deoxyribonucleoside, purines, pyrazole, pyrimidines orderivative thereof, retinoid, substituted pyrrole, or a combination thereof.

139. The pharmaceutically acceptable salt of claim 138, wherein the pharmaceutical compound comprises apadenoson, asunaprevir, azilsartan medoxomil, benzthiazide, bromfenac, candesartan cilexetil, carbazochrome, chlorambucil, chlorothiazide, cladribine, clofarabine, clonazepam, CVT-6883, CX516, dacarbazine, diazoxide, emodepside, fimasartan, flubendazole, flucytosine, fludiazepam, flunitrazepam, ganciclovir, gliclazide, glisoxepide, grazoprevir, guanosine, ibudilast, ibuproxam, iocetamic acid, iopamidol, iopanoic acid, isatoribine, ixazomib, MB-07803, nateglinide, nepafenac, OPC-51803, pleconaril, pomalidomide, pralnacasan, pyrvinium, regadenoson, rimonabant, selexipag, simeprevir, sulfadimethoxine, sulfamerazine,sulfameter, sulfamethizole, sulfamethoxazole, sulfametopyrazine, sulfamoxole, taranaban t,tazarotene, tiopronin, tolazamide, trapidil, uracil mustard, or a combination thereof.

140. The pharmaceutically acceptable salt of any one of claims 124-134, wherein thepharmaceutical compound has a pKa of about 2 to about 3.

141. The pharmaceutically acceptable salt of claim 140, wherein the pharmaceutical compound comprises azobenzene, azole, benzazepine, benzene, benzodiazepine, benzothiazine, benzothiazole, carboxylic acid, depside, diazanaphthalene, diazine, imidazopyrimidine, indole, isoindole, lactam, macrolides naphthalene, nucleoside and nucleotide analogue, organooxygen compound, piperidine, prenol lipid, pteridine, purine nucleoside, purine nucleotide, pyrazolopyrimidine, pyridine, pyrimidine nucleoside, pyrrolopyridine, quinoline, steroid, thienodiazepine, triazine, triazolopyrimidine, or a combination thereof.

142. The pharmaceutically acceptable salt of claim 141, wherein the pharmaceutical compound comprises 1,4-benzodiazepine, amino acid, peptide, aminotriazine, androstaneAttorney Docket No.: 53160-716.601 steroid, anilide, aniline, benzazepine, benzenesulfonamide, benzenesulfonyl compound, benzodiazine, benzoic acids, beta lactam, biphenyl, carbazole, diphenylether, diphenylmethane, epothilones estrane steroid, ether, halobenzene, isoindoline, milbemycin, monoterpenoid, nitroquinolines, oxosteroid, phenoxyacetic acid derivative, phenylbutylamine, phenylcarbamicacid ester, phenylmethylamine, phenylpropane, phenylquinoline, pterins, purine 2',3' -dideoxyribonucleoside, purine ribonucleotide, purines and purine derivative, pyrazole, pyrazolo[3,4-d]pyrimidine, pyridinecarboxylic acids, pyrimidines and pyrimidine derivative, sulfanilide, or a combination thereof.

143. The pharmaceutically acceptable salt of claim 141 or 142, wherein the pharmaceutical compound comprises aciclovir, adipiplon, alisertib, allopurinol, ambrisentan, amelubant, aminobenzoic acid, aminopterin, aminosalicylic acid, amprenavir, anastrozole, arsanilic acid, asoprisnil, benzocaine, BMS-488043, brecanavir, bromazepam, bumetanide, butamben, cangrelor, cefixime, cefpiramide, chromium picolinate, cidofovir, ciluprevir, cinalukast, clazosentan, clotiazepam, cloxazolam, dabrafenib, dapsone, darunavir, delorazepam, diazepam, didanosine, dutasteride, edotecarin, efonidipine, elacytarabine, entecavir, epirizole, epothilone d, finasteride, fluconazole, flutemetamol (18F), folic acid, fomepizole, fosamprenavir, ganstigmine, GW-501516, halazepam, indocyanine green, inosine, iodamide, iopromide, isavuconazole, ixabepilone, KOS-1584, KP-1461, lenalidomide, letrozole, leucovorin, levoleucovorin, macitentan, meradimate, mercaptopurine, methotrexate, methylene blue, methylthioninium, motexafin gadolinium, motexafin lutetium, moxidectin, naxifylline, nitrazepam, nitroxoline, olaparib, ombitasvir, OT-551, padimate O, paritaprevir, patupilone, penciclovir, phenyl aminosalicylate, PPL-100, pralatrexate, quazepam, ravuconazole, regorafenib, regrelor, ritonavir, roflumilast, roxadustat, silver sulfadiazine, sorafenib, stanozolol, sulfabenzamide, sulfacetamide, sulfacytine, sulfadiazine, sulfadoxine, sulfamerazine, sulfamethazine, sulfanilamide, sulfaphenazole, sulfapyridine, sulfasalazine, sulfathiazole, sulfisoxazole, talnetant, tasosartan, technetium tc-99m disofenin, technetium tc-99m mebrofenin, tezosentan, ticagrelor, tirapazamine, troxacitabine, trypan blue, voriconazole, or a combination thereof.

144. The pharmaceutically acceptable salt of any one of claims 124-134, wherein thepharmaceutical compound has a pKa of about 3 to about 4.

145. The pharmaceutically acceptable salt of claim 144, wherein the pharmaceutical compound comprises a 1,4-benzodiazepine, amino acid, peptide, anilide, aniline and substituted aniline, anisole, aryl thioether, benzodiazine, benzofuranone, benzoic acids and derivative, benzophenone, beta lactam, biphenyls and derivative, bipyridines and oligopyridine, carbodiimide, diphenylether, diphenylmethane, epothilones estrane steroid, ether, haloquinoline,Attorney Docket No.: 53160-716.601 hexacarboxylic acids and derivative, imidazole, isoindole, milbemycin, morpholine, phenoxyacetic acid derivative, phenylmethylamine, phenylpyridine, piperazine, pterins and derivative, purine 2’,3’-dideoxyribonucleoside, purines and purine derivative, purines and purine derivative, pyrazine, pyrazole, pyridine carboxaldehyde, pyridinecarboxylic acids and derivative, pyridinesulfonamide, pyridyltriazole, steroid ester, sulfanilide, sulfinylbenzimidazole, or a combination thereof.

146. The pharmaceutically acceptable salt of claim 144 or 145, wherein the pharmaceutical compound comprises adenosine, amiloride, aminobenzoic acid, aminophenazone, anagrelide, aprepitant, arsanilic acid, azathioprine, aztreonam, benzocaine, benzonatate, bisacodyl, bromazepam, brotizolam, bumetanide, butamben, calcium carbimide, cefepime, cefixime, cefmenoxime, cefotaxime, cefpodoxime, ceftizoxime, ceftriaxone, chloroxine, chromium picolinate, clioquinol, dabigatran etexilate, dabrafenib, dexlansoprazole, dexrazoxane, diazepam, didanosine, diiodohydroxyquinoline, entecavir, etofibrate, etravirine, ezogabine, flumazenil, flutemetamol (18F), indocyanine, inosine, inositol nicotinate, iopodic acid, irbesartan, isocarboxazid, isocarboxazid, isoniazid, itraconazole, ixabepilone, lansoprazole, leucovorin, levoleucovorin, levomefolic acid, lobeglitazone, losartan, lumacaftor, mazindol, mebendazole, mercaptopurine, mercaptopurine, methotrexate, metronidazole, metronidazole, montelukast, montelukast, moxidectin, nelarabine, niacin, nicorandil, nicotinamide, norelgestromin, norgestimate, oxfendazole, padimate o, pantoprazole, penciclovir, perampanel, picosulfuric acid, piroxicam, posaconazole, pralatrexate, prazepam, procaine merethoxylline, pyridoxal, pyridoxal phosphate, riociguat, ritonavir, stanozolol, talniflumate, tasosartan, tenofovir disoproxil, thiabendazole, thonzonium, ticagrelor, tinidazole, tioguanine, topiroxostat, torasemide,triamterene, triamterene, vemurafenib, vemurafenib, vismodegib, or a combination thereof.

147. The pharmaceutically acceptable salt of any one of claims 124-130, wherein thepharmaceutical compound has a pKa of about 4 to about 5.

148. The pharmaceutically acceptable salt of claim 147, wherein the pharmaceutical compound comprises 1,4-benzodiazepine, 1-ribosyl-imidazolecarboxamide, 2- benzimidazolylcarbamic acid ester, 8-hydroxyquinoline, amine, amino acid, peptide, androstane steroid, anilide, aniline and substituted aniline, anthraquinone, aryl thioether, benzodiazine,benzoic acids and derivative, beta lactam, biphenyls and derivative, bipyridine , oligopyridine,bisphosphonate, carbonyl compound, diphenylmethane, ether, hexacarboxylic ac ids andderivative, imidazole, imidazoquinoline, indolequinone, naphthyridine, oxosteroid, phenethylamine, phenylbenzimidazole, phenylhydrazine, phenylpiperidine, phenylpyridine,phenylquinoline, pterins and derivative, purine ribonucleotide, purines and p urine derivative,Attorney Docket No.: 53160-716.601 pyrazolo[1,5-a]pyrimidine, pyridine carboxaldehyde, pyridinecarboxylic acids and derivative, pyridinesulfonamide, pyridoindole, quinoline carboxylic acid, styrene, sulfinylbenzimidazole, trifluoromethylbenzene, or a combination thereof.

149. The pharmaceutically acceptable salt of claim 147 or 148, wherein the pharmaceuticalcompound comprises azathioprine, abiraterone, acadesine, adenosine 5' -phosphosulfate,adenosine monophosphate, AICA ribonucleotide, albendazole, amfecloral, aminoglutethimide, aminohippuric acid, amrinone, atazanavir, aztreonam, banoxantrone, binodenoson, bisacodyl, carfilzomib, cefditoren, cefepime, cefmenoxime, cefotaxime, cefpodoxime, ceftazidime,ceftibuten, ceftizoxime, ceftriaxone, coenzyme A, dexlansoprazole, ensulizo le, erlotinib,esomeprazole, estazolam, etizolam, etomidate, etoricoxib, etravirine, fiboflapon, flavin adenine dinucleotide, florbetaben (18F), florbetapir (18F), geldanamycin, gentian violet, hexocyclium, idelalisib, implitapide, indium In-111 oxyquinoline, inositol nicotinate, iopodic acid, irbesartan, lansoprazole, levosimendan, loratadine, lornoxicam, losartan, LX-2931, methoxyamine, metyrapone, mifepristone, milrinone, minoxidil, nalidixic acid, niacin, ocinaplon, omeprazole, OSI-930, oxibendazole, oxyquinoline, perampanel, piclidenoson, picosulfuric acid, pitavastatin, porfiromycin, PX-12, pyridoxal, pyridoxal phosphate, rabeprazole, repaglinide, resiquimod, retaspimycin, ridogrel, riluzole, risedronate, rivoglitazone, rosoxacin, S-8510, sapropterin, tecadenoson, tenofovir disoproxil, tenoxicam, thiabendazole, torasemide, triazolam, tucidinostat, ulipristal, varlitinib, vatalanib, verteporfin, verubulin, vidarabine, vipadenant, vorapaxar, or a combination thereof.

150. The pharmaceutically acceptable salt of any one of claims 124-134, wherein thepharmaceutical compound has a pKa of about 5 to about 6.

151. The pharmaceutically acceptable salt of claim 150, wherein the pharmaceutical compound comprises a 1,4-benzodiazepine, 1-ribosyl-imidazolecarboxamide, 2- benzimidazolylcarbamic acid ester, 8-hydroxyquinoline, amine, amino acid, peptide, androstane steroid, anilide, aniline and substituted aniline, anthraquinone, aryl thioether, benzodiazine, benzoic acid, beta lactam, biphenyl, bipyridines and oligopyridine, bisphosphonate, diphenylmethane, ether, hexacarboxylic acid, imidazole, imidazoquinoline, indolequinone, naphthyridine, oxosteroid, phenethylamine, phenylbenzimidazole, phenylhydrazine, phenylpiperidine, phenylpyridine, phenylquinoline, pterin, purine ribonucleotide, purines and purine derivative, pyrazolo[1,5-a]pyrimidine, pyridine carboxaldehyde, pyridinecarboxylic acid, pyridinesulfonamide, pyridoindole, quinoline carboxylic acid, styrene, sulfinylbenzimidazole, trifluoromethylbenzene, or a derivative thereof, or a combination thereof.Attorney Docket No.: 53160-716.601 152. The pharmaceutically acceptable salt of claim 150 or 151, wherein the pharmaceutical compound comprises 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, 5- methyltetrahydrofolic acid, abacavir, adefovir dipivoxil, adenine, alprazolam, ALT-2074, amdoxovir, apilimod, adenosine triphosphate, avanafil, axitinib, azelnidipine, benazepril, benzimidazole, bicisate, biricodar dicitrate, brilliant green, cabozantinib, capravirine, carbidopa, cefapirin, cerivastatin, cilazapril, cisplatin, clevidipine, clonixin, clopidogrel, cocarboxylase, dapivirine, delamanid, dersalazine, dolasetron, elbasvir, enalapril, ethionamide, etifoxine, etozoline, famciclovir, felodipine, floctafenine, fominoben, fosaprepitant, GTS-21, hetacillin, imidacloprid, imiquimod, incadronic acid, indibulin, isosulfan blue, isradipine, kinetin, lamotrigine, ledipasvir, linsitinib, meclinertant, mesalazine, methenamine, moexipril, morniflumate, NADH, nevirapine, nifedipine, niflumic acid, nimodipine, nisoldipine, nitrendipine, olmesartan, pazopanib, peldesine, perindopril, phenelzine, picoplatin, pinacidil, pioglitazone, pipecuronium, pradefovir mesylate, prasugrel, prinomastat, procarbazine,pyridoxine, quinapril, ramipril, rilpivirine, rostaporfin, ruxolitinib, seliciclib , sildenafil,sonidegib, spirapril, stannsoporfin, talmapimod, taribavirin, temocapril, temoporfin, tenofovir alafenamide, thiamine, trandolapril, tropicamide, velpatasvir, ximelagatran, zinc picolinate, zolpidem, or a combination thereof.

153. The pharmaceutically acceptable salt of any one of claims 124-129, wherein thepharmaceutical compound has a pKa of about 6 to about 7.

154. The pharmaceutically acceptable salt of claim 153, wherein the pharmaceutical compound comprises 1,4-benzodiazepine, 1-ribosyl-imidazolecarboxamide, 2- benzimidazolylcarbamic acid ester, 8-hydroxyquinoline, amine, amino acid, peptide, androstane steroid, anilide, aniline and substituted aniline, anthraquinone, aryl thioether, benzodiazine, benzoic acid, beta lactam, biphenyl, bipyridines and oligopyridine, bisphosphonate, carbonyl compound, diphenylmethane, ether, hexacarboxylic acid, imidazole, imidazoquinoline, indolequinone, naphthyridine, oxosteroid, phenethylamine, phenylbenzimidazole, phenylhydrazine, phenylpiperidine, phenylpyridine, phenylquinoline, pterin, purine ribonucleotide, purines and purine derivative, pyrazolo[1,5-a]pyrimidine, pyridine carboxaldehyde, pyridinecarboxylic acid, pyridinesulfonamide, pyridoindole, quinoline carboxylic acid, styrene, sulfinylbenzimidazole, trifluoromethylbenzene, or a derivative thereof, or a combination thereof.

155. The pharmaceutically acceptable salt of claim 153 or 154, wherein the pharmaceutical compound comprises 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, 5- methyltetrahydrofolic acid, abacavir, adefovir dipivoxil, adenine, alprazolam, ALT-2074,Attorney Docket No.: 53160-716.601 amdoxovir, apilimod, avanafil, azelnidipine, benazepril, benzimidazole, bicisate, biricodardicitrate, brilliant green, capravirine, carbidopa, cerivastatin, cilazapril, cisplatin, clevid ipine,clonixin, clopidogrel, cocarboxylase, dapivirine, delamanid, dersalazine, dolasetron, elbasvir, enalapril, etifoxine, etozoline, famciclovir, felodipine, floctafenine, fominoben, fosaprepitant, GTS-21, hetacillin, imidacloprid, imiquimod, incadronic acid, indibulin, isosulfan blue, isradipine, kinetin, lamotrigine, ledipasvir, meclinertant, mesalazine, methenamine, moexipril, morniflumate, nevirapine, nifedipine, niflumic acid, nimodipine, nisoldipine, nitrendipine, olmesartan, pazopanib, peldesine, perindopril, phenelzine, picoplatin, pinacidil, pioglitazone, pipecuronium, pradefovir mesylate, prasugrel, prinomastat, procarbazine, pyridoxine, quinapril, ramipril, rilpivirine, rostaporfin, ruxolitinib, seliciclib, sildenafil, sonidegib, spirapril, stannsoporfin, talmapimod, taribavirin, temocapril, temoporfin, tenofovir alafenamide, thiamine, trandolapril, tropicamide, velpatasvir, ximelagatran, zinc picolinate, zolpidem, acarbose, ajmaline, alcaftadine, alfentanil, alfuzosin, almitrine, amisulpride, amoxicillin, ampicillin, amrubicin, antrafenine, aripiprazole, asenapine, atipamezole, azaperone, bacampicillin, cefaclor, cefadroxil, cefdinir, cefprozil, cephalexin, cephaloglycin, chlordiazepoxide, clozapine, dalfopristin, dasatinib, diethylpropion, domperidone, dorzolamide, doxapram, doxazosin, drotaverine, efinaconazole, eprazinone, flavoxate, flibanserin, flupirtine, imidafenacin, indinavir, ketamine, ketotifen, lapatinib, loxapine, mepivacaine, methacycline, moxonidine, nefazodone, oftasceine, olanzapine, ondansetron, phendimetrazine, pivampicillin, pramocaine, prazosin, quetiapine, ranolazine, rupatadine, setiptiline, terazosin, tetrabenazine, ticlopidine, tizanidine, tofacitinib, trazodone, trimethoprim, valaciclovir, valganciclovir, ziprasidone, or a combination thereof.

156. The pharmaceutically acceptable salt of claim 125-132, wherein the pharmaceutical compound has a pKa of about 7 to about 8.

157. The pharmaceutically acceptable salt of claim 156, wherein the pharmaceutical compound comprises an ajmaline-sarpagine alkaloid, 1,4-benzodiazepine, 2,3,5-trisubstituted thiophene, alcohols and polyol, amine, amino acid or peptide, anilide, anisole, benzazepine, benzazocine, benzene, benzimidazole, benzocycloheptapyridine, benzodiazepine, benzodiazine, benzofuran, benzoic acid, benzothiadiazole, benzothiazepine, benzotriazole, benzoxazepine, benzoxepine, benzylamine, benzylisoquinoline, benzylpiperidine, beta lactam, biphenyl, carbazole, carbohydrate, carbonyl compound, carboxylic acid, cycloheptathiophene, diarylheptanoid, diazanaphthalene, diazinane, diazine, dibenzocycloheptene, dibenzodiazepine, dibenzothiazepine, dibenzoxazepine, dibenzoxepine, diphenylmethane, ergolin, flavone, flavonoid, halobenzene, hybrid peptide, hydropyridine, indane, indole, indoline, isoquinoline,Attorney Docket No.: 53160-716.601 isoquinolone, lactam, linear diarylheptanoid, lysergic acid, macrolactam, macrolide lactam, monoterpenoid, morpholine, n-acylpiperidine, n-alkylindole, naphthacene, naphthopyranone, naphthopyran, n-phenylurea, organonitrogen compound, organooxygen compound, oxazinane, pentacarboxylic acid, peptidomimetic, phenanthrene, phenethylamine, phenol ether, phenylmethylamine, phenylpiperidine, phenyltropane, piperazine, piperidinecarboxylic acid, piperidine, polypeptide, prenol lipid, pyridazines and derivative, pyridine, pyrimidine 2'- deoxyribonucleoside, pyrimidine nucleoside, pyrimidine, quinoline carboxylic acid, quinoline, steroid ester, steroid, tetracenequinone, tetracycline, tetrahydroisoquinoline, thienopyridine, thiophene, tropane alkaloid, xylene, yohimbine alkaloid, or derivatives thereof, or a combination thereof.

158. The pharmaceutically acceptable salt of claim 156 or 157, wherein the pharmaceuticalcompound comprises acarbose, ajmaline, alcaftadine, alfentanil, alfuzosin, alizapride, almitrine ,almorexant, altretamine, altropane, alvocidib, amdinocillin, aminolevulinic acid, amisulpride, amoxicillin, ampicillin, amrubicin, antrafenine, aripiprazole, asenapine, atipamezole, AV-412, azaperone, azatadine, bacampicillin, barnidipine, benidipine, bifeprunox, bleomycin, blonanserin, bradanicline, brifentanil, bupivacaine, buspirone, cariporide, cariprazine, casopitant, cathinone, cefaclor, cefadroxil, cefdinir, cefprozil, cefradine, cephalexin, cephaloglycin, cethromycin, cetirizine, chlorcyclizine, chlordiazepoxide, chlortetracycline, cilansetron, clozapine, dalfopristin, dapiprazole, dasatinib, deserpidine, diethylpropion, domperidone, dorzolamide, dovitinib, doxapram, doxazosin, doxycycline, drotaverine, edonerpic, efinaconazole, elsamitrucin, eluxadoline, enalaprilat, enzastaurin, eprazinone, ergonovine, ergotamine, EVT-101, ezatiostat, facinicline, fenproporex, finafloxacin, flavoxate, flibanserin, flunarizine, flupirtine, hexaminolevulinate, hydroxyzine, iclaprim, iloperidone, imidafenacin, indinavir, josamycin, ketamine, ketotifen, lapatinib, larazotide, lesopitron, levobupivacaine, levocetirizine, lidocaine, linaclotide, lofexidine, loracarbef, lorpiprazole,loxapine, lysergic acid diethylamide, manidipine, mepiprazole, mepivacaine, methacycline,methyl aminolevulinate, methylergometrine, methysergide, miglitol, motesanib, moxonidine, naloxone, naluzotan, nefazodone, netupitant, oftasceine, olanzapine, onalespib, ondansetron, oxytetracycline, palonosetron, perospirone, phendimetrazine, phenoxybenzamine, pirenzepine,pivampicillin, pivmecillinam, pizotifen, pramocaine, prazosin, priralfinamide, prx -08066,pyrimethamine, quetiapine, RAF-265, raloxifene, ranolazine, reboxetine, remifentanil, rescinnamine, reserpine, rifampicin, rifapentine, rocuronium, ropivacaine, rupatadine, safinamide, saxagliptin, setiptiline, SNX-5422, solithromycin, sufugolix, SUVN-502, talactoferrin alpha, telithromycin, terazosin, tetrabenazine, ticlopidine, tipifarnib, tizanidine,Attorney Docket No.: 53160-716.601 tofacitinib, trabectedin, trazodone, trimethoprim, trimetrexate, tymazoline, valaciclovir, valganciclovir, valomaciclovir, valtorcitabine, venetoclax, voglibose, yohimbine, ziprasidone, zosuquidar, or a combination thereof.

159. The pharmaceutically acceptable salt of any one of claims 125-132, wherein thepharmaceutical compound has a pKa of about 8 to about 9.

160. The pharmaceutically acceptable salt of claim 159, wherein the pharmaceutical compound comprises 1-benzopyran, 1-benzothiopyran, 1-phenyltetrahydroisoquinoline, alcohol, polyol, amine, amino acid, peptide, aminoquinoline and derivative, androstane steroid, anilide, anisole, aryl thioether, benzenediol, benzenesulfonamide, benzo-1,4-dioxane, benzodiazine, benzoic acid and derivative, benzoquinoline, benzylamine, benzylether, benzylpiperidine, beta lactam, biphenyl and derivative, carbazole, carbohydrate and carbohydrate conjugate, carbonyl compound, carboxylic acid derivative, depsipeptide, dibenzazepine, dibenzothiepin, dibenzoxazepine, diphenylacetonitrile, diphenylfuran, diphenylmethane, ether, fatty acid and conjugate, fentanyl, galanthamine-type amaryllidaceae alkaloid, halobenzene, hydropyridine, imidazolidine, indazole, indole, indoloquinoline, isoquinolone and derivative, isoxazoline, lysergic acid and derivative, methoxybenzene, monoterpenoid, morpholine, n-alkylindole, naphthyridine, oxadiazole, pentacarboxylic acid and derivative, phenethylamine, phenothiazine, phenoxazine, phenoxy compound, phenylmethylamine, phenylnaphthalene, phenylpiperidine, phenylpropane, phenylpyridine, phenylpyrrolidine, phenylquinoline, piperazine, piperidinecarboxylic acid and derivative, purine, pyrimidine and pyrimidine derivative, pyrrolidinylpyridine, quinoline carboxamide, quinoline carboxylic acid, styrene, substituted pyrrole, sulfanilide, tetracarboxylic acid and derivative, thiazole, thiophene carboxylic acid andderivative, trifluoromethylbenzene, xylene, or a derivative thereof, or a combination thereof.

161. The pharmaceutically acceptable salt of claim 159 or 160, wherein the pharmaceutical compound comprises aceprometazine, acetophenazine, aclarubicin, acrivastine, afatinib, afimoxifene, alanosine, amiodarone, ammonia n-13, ammonium molybdate, amonafide, amorolfine, amoxapine, amsacrine, amylocaine, anamorelin, anileridine, aplindore, apraclonidine, articaine, arzoxifene, asimadoline, aspartame, astemizole, atrasentan, azelastine, azimilide, bedaquiline, benzylfentanyl, bosutinib, brexpiprazole, brimonidine, bromodiphenhydramine, buclizine, budiodarone, bupivacaine, bupropion, butyrfentanyl, caldaret, captodiame, carbinoxamine, carfentanil, carvedilol, cefminox, cefotiam, celgosivir, cevimeline, chlorcyclizine, chloroprocaine, chloropyramine, chlorotoxin I-131, cinnarizine, ciprofloxacin, cisapride, clarithromycin, clofedanol, clomocycline, clonidine, cloperastine, CNS- 5161, cocaine, cyclacillin, cyclizine, cyclopentolate, cycloserine, cyproheptadine, darapladib,Attorney Docket No.: 53160-716.601 daunorubicin, DDP-225, demeclocycline, deramciclane, desvenlafaxine, dicyclomine, dihydroergotamine, diltiazem, dimenhydrinate, dimetotiazine, diphenhydramine, diphenoxylate,diphenylpyraline, dofetilide, donepezil, dotarizine, doxorubicin, doxylamine, droxidopa, d -serine, dyclonine, edetic acid, edivoxetine, elacridar, eletriptan, eliglustat, emedastine, enoxacin, eperisone, epinastine, epinephrine, epirubicin, erythromycin, ethoheptazine, famotidine, fasudil, fentanyl, flupentixol, fluphenazine, flurazepam, forodesine, friulimicin B, gaboxadol, gadoversetamide, galantamine, garenoxacin, gatifloxacin, glesatinib, glucosamine, glypromate, granisetron, grepafloxacin, haloperidol, hydrocodone, hydromorphone, idarubicin, imatinib, imolamine, indium In-111 pentetate, iroxanadine, isoaminile, isoprenaline, isothipendyl, isoxsuprine, istaroxime, itopride, ketobemidone, lasofoxifene, l-asparagine, levobupivacaine, levonordefrin, lincomycin, lobeline, lofentanil, lomefloxacin, l-threonine, lucanthone, lumateperone, lurasidone, LY-517717, managlinat dialanetil, masitinib, meclizine, melperone,mepyramine, mequitazine, mesoridazine, methdilazine, midodrine, migalastat, miglustat,mimosine, minocycline, moxisylyte, naloxegol, nebivolol, nelfinavir, nicardipine, nicergoline, nicotine, norepinephrine, norfloxacin, normethadone, ocaperidone, ohmefentanyl, orphenadrine, osimertinib, oxybuprocaine, oxybutynin, oxycodone, oxyphencyclimine, pafuramidine, palbociclib, paliperidone, paliroden, pargyline, PBT-1033, pelitinib, pentetate calciumtrisodium, pentetate zinc trisodium, pentostatin, perphenazine, pethidine, p -fluorofentanyl,phenindamine, phenmetrazine, phenyltoloxamine, pimavanserin, pimozide, pipamperone, pipazethate, pipendoxifene, pipotiazine, pirlindole, ponatinib, PPI-1019, prilocaine, procaine, prochlorperazine, proflavine, proparacaine, propericiazine, propiomazine, propoxycaine, protokylol, prucalopride, PRX-07034, quinagolide, quinupristin, rabeximod, ranitidine, rasagiline, remacemide, remoxipride, renzapride, rifabutin, rifalazil, rilapladib, risperidone, rivastigmine, robalzotan, rolapitant, rolitetracycline, roxatidine acetate, saquinavir, sarafloxacin, sarizotan, selegiline, serine, sertindole, sincalide, sitagliptin, solifenacin, sparfloxacin, spinosad, sufentanil, sulpiride, tacrine, talabostat, tamoxifen, tariquidar, technetium tc-99m tetrofosmin, tegaserod, terbinafine, terconazole, tetracaine, tetracycline, tetrofosmin, thienylfentanyl, thioproperazine, thioridazine, thiothixene, thonzylamine, tianeptine, tigecycline, tocainide, tolperisone, toremifene, trifluoperazine, trimebutine, trimethobenzamide, tripelennamine, triprolidine, tromethamine, tubocurarine, udenafil, vanoxerine, veliparib, venlafaxine, vicriviroc, vilazodone, viloxazine, vinblastine, vincristine, vindesine, vinorelbine, voacamine, vortioxetine, xaliproden, xanthinol, zanapezil, zotepine, zuclopenthixol, α-methylfentanyl, α- methylthiofentanyl, β-hydroxythiofentanyl, or a combination thereof.Attorney Docket No.: 53160-716.601 162. The pharmaceutically acceptable salt of any one of claims 125-132, wherein thepharmaceutical compound has a pKa of about 9 to about 10.

163. The pharmaceutically acceptable salt of claim 162, wherein the pharmaceutical compound comprises a 1-benzopyran, 1-benzothiopyran, 1-hydroxy-4-unsubstituted benzenoid, 4-quinolinemethanol, 5’-deoxy-5’-thionucleoside, amine, amino acid, peptide, aminophenyl ether, aminoquinoline, anilide, anisole, anthraquinone, benzenediol, benzenesulfonamide, benzo-1,4-dioxane, benzodiazine, benzoic acid, benzonitrile, benzoquinoline, benzoxazinone, benzoyl, benzyl alcohol, benzylether, benzylpiperidine, beta lactam, biphenyl, bisphosphonate, carbazole, carbohydrate and carbohydrate conjugate, cytisine, depsipeptide, dibenzazepine, dibenzothiepin, dibenzoxepine, dicarboxylic acid, diphenylacetonitrile, diphenylmethane, diterpenoid, ether, fentanyl, glycerophosphoserine, halobenzene, hybrid peptide, hydropyridine, hydroquinoline, hydroxypyridine, indazole, indolecarboxylic acid, indole, indoline, indoloquinoline, indolyl carboxylic acid, isoquinoline quinone, lysergic acid, methoxybenzene, naphthyridine, nitrobenzene, nitroquinoline, organosulfonic acid, pentacarboxylic acid, phenethylamine, pheniramine, phenothiazine, phenoxazine, phenoxy compound, phenoxyacetic acid, phenylacetamide, phenylbutylamine, phenylmethylamine, phenylpiperidine,phenylpropane, phenyltropane, piperazine, piperidinecarboxylic acid, pregnane steroid, purinesand purine, pyridinium, quinoline carboxylic acid, quinolone, steroid ester, styrene, substituted pyrrole, sulfanilide, tametraline, thiophene carboxylic acid, toluene, trifluoromethylbenzene, tryptamine, tyrosol, or a derivative thereof, or a combination thereof.

164. The pharmaceutically acceptable salt of claim 162 or 163, wherein the pharmaceutical compound comprises (3S)-3-methyl-D-aspartic acid, isoxsuprine, 13-deoxydoxorubicin, 3- allylfentanyl, 3-methylfentanyl, 4-phenylfentanyl, 7-hydroxystaurosporine, acebutolol, ademetionine, aldoxorubicin, alendronic acid, alethine, alimemazine, aliskiren, almotriptan, alogliptin, alprenolol, ambroxol, amibegron, amikacin, amineptine, aminocandin, amitriptyline, amlodipine, amphotericin b, antazoline, apramycin, aprindine, arbaclofen, arbekacin, arbutamine, arformoterol, arimoclomol, arotinolol, arylacenamide, atenolol, atomoxetine, atosiban, atropine, azithromycin, bacitracin, baclofen, bambuterol, bazedoxifene, becatecarin, benfluorex, benzatropine, benzphetamine, benzydamine, benzylpenicilloyl polylysine, bepotastine, bepridil, besifloxacin, betahistine, betaxolol, betazole, bevantolol, bilastine, bimoclomol, biperiden, bisoprolol, bopindolol, brasofensine, bromhexine, bromopride, brompheniramine, bufuralol, bupranolol, butenafine, cabergoline, canfosfamide, carbocisteine, carteolol, caspofungin, cediranib, ceforanide, ceftolozane, celiprolol, chlorphenamine, chlorpromazine, chlorprothixene, cilastatin, cinchocaine, cinitapride, citalopram, clemastine,Attorney Docket No.: 53160-716.601 clenbuterol, clocapramine, clofazimine, clomifene, clomipramine, cobimetinib, codeine, colestipol, CP-122721, cyamemazine, cyclobenzaprine, cycrimine, cystine, cytisine,dalbavancin, dapoxetine, daptomycin, darinaparsin, declopramide, demexiptiline, desloratadine ,dexbrompheniramine, dexchlorpheniramine maleate, dexmethylphenidate, dextromethorphan, dextropropoxyphene, dextrothyroxine, dezocine, difenoxin, dihydrocodeine, dimetacrine, dimetindene, diphenidol, dipivefrin, diprenorphine, dirithromycin, D-methionine, dobutamine, dopamine, doripenem, dosulepin, doxepin, dronedarone, duloxetine, encainide, enclomiphene, ephedrine, epicept NP-1, eribulin, ertapenem, escitalopram, esmolol, ethambutol, ethopropazine, ethylmorphine, etidocaine, etryptamine, fenoterol, fenspiride, ferrous bisglycinate, fexofenadine, filanesib, fingolimod, flecainide, fluoxetine, fluspirilene, fluvoxamine, formoterol, framycetin, gabapentin, gadobenic acid, gadofosveset trisodium, gadopentetate dimeglumine, gadoteridol, gadoxetic acid, gemifloxacin, glutamic acid, glutathione, glutathione disulfide, glycine, golotimod, gosogliptin, granisetron, halofuginone, heroin, hexetidine, hexylcaine, histamine, histidine, homatropine, huperzine A, huperzine B, hydroxyamphetamine, hydroxychloroquine, hyoscyamine, ibandronate, ifenprodil, imipramine, indacaterol, ioflupane I-123, irinotecan, isoetarine, ispinesib, ivabradine, K201, kanamycin, labetalol, L-alanine, L-aspartic acid, L- citrulline, L-cysteine, lercanidipine, leukotriene C4, levallorphan, levamlodipine, levobetaxolol, levobunolol, levodopa, levomethadyl acetate, levomilnacipran, levorphanol, levothyroxine, L- glutamine, linagliptin, liothyronine, liotrix, L-isoleucine, LJP 1082, L-leucine, lomitapide, loperamide, L-phenylalanine, L-threonine, L-tryptophan, L-tyrosine, lumefantrine, L-valine, lymecycline, mafenide, magnesium glycinate, mefloquine, melphalan, meropenem, metaraminol, methadone, methadyl acetate, methionine, methotrimeprazine, methoxamine, methyldopa, methylphenidate, metipranolol, metixene, metoclopramide, metoprolol, metyrosine, mexiletine, mibefradil, milnacipran, mirabegron, mitemcinal, mitoxantrone, mn-305, morphine, moxifloxacin, nadolol, naftifine, nalmefene, naratriptan, naronapride, natamycin, nemonoxacin, netilmicin, nitroarginine, NPS-2143, NS-2359, nystatin, oglufanide, olodaterol, olopatadine, omacetaxine mepesuccinate, OPC-28326, orciprenaline, osanetant, oseltamivir, oxamniquine, oxilofrine, oxitriptan, oxprenolol, pamidronate, paromomycin, paroxetine, penbutolol, penicillamine, pentoxyverine, pergolide, phenaridine, phenindamine, pheniramine, phentolamine, phenylephrine, phenylpropanolamine, pholcodine, phosphatidyl serine, piboserod, pindolol, piperazine, pirarubicin, pirbuterol, pixantrone, polaprezinc, pracinostat, practolol, procainamide, procaterol, procyclidine, promazine, promethazine, propafenone, propoxyphene napsylate, propranolol, PRX-03140, pseudoephedrine, PX-478, quarfloxin, quinidine, quinidine barbiturate, quinine, repinotan, retapamulin, ribostamycin, ritodrine,Attorney Docket No.: 53160-716.601 rizatriptan, ronacaleret, roxithromycin, salbutamol, salmeterol, saredutant, selenomethionine, seproxetine, serotonin, sertraline, sibutramine, silodosin, siramesine, solabegron, sotalol, spectinomycin, spiramycin, sumanirole, sumatriptan, sunitinib, tamsulosin, tandutinib, tapentadol, TAS-108, taurine, tedisamil, telavancin, terbutaline, terfenadine, tesmilifene, tesofensine, tetrodotoxin, TG-100801, tiagabine, ticalopride, tilmicosin, timolol, tobramycin, topotecan, tramadol, tranylcypromine, triethylenetetramine, triflupromazine, trihexyphenidyl, trimetazidine, trimipramine, trovafloxacin, tyramine, ubenimex, vancomycin, vandetanib, varenicline, vecuronium, verapamil, vernakalant, vigabatrin, vilanterol, vildagliptin, zolmitriptan, α-methylacetylfentanyl, α-methylfentanyl, β-methylfentanyl, or a combination thereof.

165. The pharmaceutically acceptable salt of any one of claims 125-132, wherein thepharmaceutical compound has a pKa of about 10 to about 13.

166. The pharmaceutically acceptable salt of claim 165, wherein the pharmaceutical compound comprises 2,6-dimethyl-3-benzazocine, alkaline earth metal oxide, alkylthiol, amine, amino acid, peptide, aminopyridine, aminoquinoline, benzenediol, benzoic acid, benzoquinoline, beta lactam, bile acid, alcohol, biphenyl, bisphosphonate, carbazole, carbohydrates and carbohydrate conjugate, carboxylic acid derivative, cyclohexylamine, depsipeptide, dibenzazepine, diphenylmethane, ether, fatty acids and conjugate, guanidine, halobenzene, hybrid peptide, indolecarboxylic acid, indole, indoline, monoterpenoid, n-arylamide, organosulfonic acid, peptoid-peptide hybrid, phenethylamine, pheniramine, phenylbutylamine, phenylmethylamine, phenylpiperidine, phenylpropane, phenylpropylamine, phenylpyridine, piperidinecarboxylic acid, purines and purine derivative, pyrazolylpyridine, pyrimidines and pyrimidine derivative, tetracarboxylic acid, tryptamine, urea, xylene, or a derivative thereof, or a combination thereof.

167. The pharmaceutically acceptable salt of claim 165 or 166, wherein the pharmaceutical compound comprises 2-iminobiotin, abarelix, ABT-510, afamelanotide, agmatine, alverine, alvimopan, amantadine, AMD-070, amifostine, aminocaproic acid, amodiaquine, amphetamine, anatibant, apomorphine, argatroban, arverapamil, atiprimod, aviptadil, bedoradrine, benzoctamine, bethanidine, bicifadine, bivalirudin, brostallicin, buformin, buprenorphine, butorphanol, butriptyline, capreomycin, carbamide peroxide, ceftobiprole, ceritinib, cetrorelix, chlorhexidine, chloroquine, chlorphentermine, cinacalcet, corticorelin ovine triflutate, cr665, creatine, crizotinib, cysteamine, CZEN 002, dalfampridine, darifenacin, debrisoquin, deferoxamine, degarelix, delcasertib, denibulin, desipramine, deslorelin, desmopressin, dexfenfluramine, dextroamphetamine, diethylnorspermine, dihydrostreptomycin, disopyramide,Attorney Docket No.: 53160-716.601 eflornithine, enviomycin, etorphine, felypressin, fencamfamine, fenethylline, fenfluramine, fenoldopam, fesoterodine, fradafiban, frovatriptan, fursultiamine, gadoteric acid, gadoteridol, gamma-aminobutyric acid, ganirelix, gentamicin, gonadorelin, goserelin, guanadrel, guanethidine, guanidine, halofantrine, hexoprenaline, histrelin, hydroxyproline, hydroxystilbamidine isethionate, ibutilide, icatibant, imipenem, indalpine, indecainide, iobenguane, iobenguane sulfate I-123, isometheptene, labradimil, L-aminocarnityl-succinyl- leucyl-argininal-diethylacetal, lanreotide, L-arginine, L-eflornithine, levmetamfetamine, levocabastine, lisdexamfetamine, lisinopril, lixisenatide, L-lysine, lorcaserin, L-proline, magnesium oxide, maprotiline, maraviroc, mecamylamine, memantine, mephentermine, metformin, methamphetamine, midomafetamine, nafarelin, nalbuphine, naltrexone, naphazoline, neramexane, neridronic acid, nintedanib, nor-noha, nortriptyline, nylidrin, obinepitide, octreotide, olcegepant, oritavancin, ornithine, otamixaban, oxymetazoline, oxymorphone, panobinostat, pasireotide, pemetrexed, pentamidine, pentazocine, peramivir, perhexiline, phencyclidine, phenformin, phentermine, pimagedine, piracetam, plerixafor, polymyxin B sulfate, pozanicline, pramipexole, pregabalin, prezatide, primaquine, progabide, proguanil, propylhexedrine, protriptyline, pyrantel, quinacrine, ramoplanin, rifaximin, rimantadine, rivanicline, romidepsin, ropinirole, rotigotine, saralasin, satraplatin, serotonin, SGS-742, sitamaquine, SNS-032, somatostatin, spermine, SQ-109, squalamine, streptomycin, T131, tafenoquine, talotrexin, tanespimycin, tecastemizole, tenocyclidine, terlipressin, tesamorelin, tetracosactide, tetryzoline, tezampanel, tipiracil, tirofiban, tolazoline, tolterodine, tramiprosate, tranexamic acid, triptorelin, ularitide, urea C-13, vapitadine, vintafolide, viomycin, WX-UK1, xylometazoline, zanamivir, or a combination thereof.

168. The pharmaceutically acceptable salt of any one of claims 124-167, wherein the pharmaceutically acceptable salt is a solid.

169. The pharmaceutically acceptable salt of claim 168, wherein the pharmaceutical compound has a pKa of at least 2.

170. The pharmaceutically acceptable salt of claim 168, wherein the pharmaceutical compound has a pKa of about 2 to about 7.

5.

171. The pharmaceutically acceptable salt of claim 168, wherein the pharmaceutical compound has a pKa of about 1 to about 5.

172. The pharmaceutically acceptable salt of claim 168, wherein the pharmaceutical compound has a pKa of about 7.5 to about 11, 173. The pharmaceutically acceptable salt of any one of claims 124-167, wherein the pharmaceutically acceptable salt is formulated as a liquid.Attorney Docket No.: 53160-716.601 174. The pharmaceutically acceptable salt of claim 173, wherein the pharmaceutical compound has a pKa of at least 5.

175. The pharmaceutically acceptable salt of claim 173, wherein the pharmaceutical compound has a pKa of about 5 to about 7.

176. The pharmaceutically acceptable salt of any one of claims 124-175, wherein the pharmaceutically acceptable salt when formulated as a solution has a lower osmolality than a solution comprising the composition comprising a salt of the pharmaceutical compound and a salt of the complexing agent.

177. The pharmaceutically acceptable salt of any one of claims 124-176, wherein the pharmaceutically acceptable salt improves a solubility of the pharmaceutical compound by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or about 100% as compared to a composition (i) without the complexing agent or (ii) wherein the pharmaceutical compound does not complex with one of more of the acidic functional groups of the complexing agent.

178. The pharmaceutically acceptable salt of any one of claims 124-177, wherein the pharmaceutically acceptable salt improves a solubility of the pharmaceutical compound by about 2-fold, about 3-fold, about 4-fold, about 5-fold, about 6-fold, about 7-fold, about 8-fold, about 9- fold, about 10-fold, about 20-fold, about 30-fold, about 40-fold, or about 50-fold as compared to a composition (i) without the complexing agent or (ii) wherein the pharmaceutical compounddoes not complex with one of more of the acidic functional groups of the complexing agent .

179. The pharmaceutically acceptable salt of any one of claims 124-178, wherein the complexing agent comprises a substituted cyclodextrin.

180. The pharmaceutically acceptable salt of claim 179, wherein the complexing agent comprises a cyclodextrin substituted with at least one acidic functional group.

181. The pharmaceutically acceptable salt of claim 180, wherein the cyclodextrin is substituted with 3 to 8 acidic functional groups.

182. The pharmaceutically acceptable salt of claim 181, wherein the cyclodextrin is sulfobutylether-β-cyclodextrin (SBEBCD).

183. The pharmaceutically acceptable salt of claim 124, wherein the pharmaceutically acceptable salt when formulated as a solution has a lower osmolality than a solution comprising a composition comprising a salt of the pharmaceutical compound and a salt of the complexing agent.Attorney Docket No.: 53160-716.601 184. The pharmaceutically acceptable salt of claim 124, wherein the pharmaceutical is formulated for subcutaneous, intramuscular, sublingual, oral, rectal, transvaginal, or intranasal administration.

185. The pharmaceutically acceptable salt of claim 124, wherein the pharmaceutically acceptable salt when formulated as a solution has an osmolality of no more than about 850 mOsm / kg.

186. The pharmaceutically acceptable salt of claim 62, wherein the pharmaceutically acceptable salt has a pH of about 4 to about 7.

187. The pharmaceutically acceptable salt of claim 124, wherein the complexing agent is present in an amount of about 10 mg / mL to about 600 mg / mL.

188. The pharmaceutically acceptable salt of claim 124, wherein the complexing agent acts asthe counterion to between 1 to 10 molecules of the pharmaceutical compound.

189. The pharmaceutically acceptable salt of claim 124, wherein the complexing agent further comprises a non-polar pore.

190. The pharmaceutically acceptable salt of claim 189, wherein the pharmaceutically acceptable salt further comprises an additional molar equivalent of the pharmaceutical compound, wherein the additional molar equivalent of the pharmaceutical compound is unionized and complexed to the non-polar pore.

191. The pharmaceutically acceptable salt of claim 124, wherein the ratio of complexing agent to the pharmaceutical compound is about 1:1.

1.

192. The pharmaceutically acceptable salt of claim 124, wherein the ratio of complexing agent to the pharmaceutical compound is about 1:

2.

193. The pharmaceutically acceptable salt of claim 124, wherein the ratio of complexing agent to the pharmaceutical compound is about 1:

3.

194. The pharmaceutically acceptable salt of claim 124, wherein the ratio of complexing agent to the pharmaceutical compound is about 1:

4.

195. The pharmaceutically acceptable salt of claim 124, wherein the ratio of complexing agent to the pharmaceutical compound is about 1:

5.

196. The pharmaceutically acceptable salt of claim 124, wherein the ratio of complexing agent to the pharmaceutical compound is about 1:6.

5.

197. The pharmaceutically acceptable salt of claim 124, wherein the pharmaceuticalcompound has a solubility of less than about 50 mg / ml as salt in an aqueous medium.

198. The pharmaceutically acceptable salt of claim 124, wherein the pharmaceuticalcompound has a solubility of less than about 10 mg / ml as salt in an aqueous medium.Attorney Docket No.: 53160-716.601 199. The pharmaceutically acceptable salt of claim 124, wherein the pharmaceutical compound has a solubility of less than about 5 mg / ml as salt in an aqueous medium.

200. The pharmaceutically acceptable salt of claim 124, wherein the pharmaceuticalcompound has a solubility of less than about 0.5 mg / ml as salt in an aqueous medium.

201. The pharmaceutically acceptable salt of claim 124, wherein the pharmaceuticalcompound has a solubility of less than about 0.1 mg / ml as salt in an aqueous medium.

202. The pharmaceutically acceptable salt of any one of claims 74-78, wherein the pharmaceutical compound is ionized.

203. The pharmaceutically acceptable salt of claim 124, wherein the pharmaceutical compound comprises rotigotine, eletriptan, DXM, midazolam, remdesivir, copanlisib, melevodopa, tigecycline, naloxone, amikacin, 1-amantadine, 2-amantadine, rimantadine, amifampridine, rapamycin, clonidine, morphine, hydrocodone, sumatriptan, ropivacaine, bupivacaine, diphenhydramine, granistetron, deschloroketamine, 2-fluoro-deschloroketamine, or caspofungin.

204. The pharmaceutically acceptable salt of any one of claims 124-203, wherein the pharmaceutical compound comprises a GABA-ergic.

205. The pharmaceutically acceptable salt of claim 204, wherein the GABA-ergic comprises Baclofen, Gaboxidol, or Muscimol, or a combination thereof.

206. The pharmaceutically acceptable salt of any one of claims 124-203, wherein the pharmaceutical compound comprises an alpha-2 agonist.

207. The pharmaceutically acceptable salt of claim 206, wherein the alpha-2 agonist comprises Clonidine, Guanfacine, or Tizanidine, or a combination thereof.

208. The pharmaceutically acceptable salt of any one of claims 124-203, wherein the pharmaceutical compound is an ophthalmic.

209. The pharmaceutically acceptable salt of claim 208, wherein the ophthalmic comprises aceclidine, atropine, azelastine, brimonidine, cyclopentolate, ketotifen, levobunolol, olopatadine, pilocarpine, proparacaine, tetracaine, timolol, or tropicamide.

210. The pharmaceutically acceptable salt of any one of claims 124-203, wherein the pharmaceutical compound is a bisphosphonate.

211. The pharmaceutically acceptable salt of claim 210, wherein the bisphosphonate is alendronate, ibandronate, pamidronate, risedronate, zoledronic acid, or a combination or two or more thereof.

212. The pharmaceutically acceptable salt of any one of claims 124-203, wherein the pharmaceutical compound is an antibiotic.Attorney Docket No.: 53160-716.601 213. The pharmaceutically acceptable salt of claim 212, wherein the antibiotic comprises amikacin, amoxicillin, ampicillin, azithromycin, aztreonam, cefaclor, cefadroxil, cefalexin, cefazolin, cefdinir, cefditoren, cefepime, cefiderocol, cefixime, cefmetazole, cefoperazone, cefotaxime, cefotetan, cefovecin, cefoxitin, cefpodoxime, cefprozil, ceftaroline, ceftazidime, ceftibuten, ceftizoxime, ceftolozane, ceftriaxone, cefuroxime, cephalexin, cephalothin, cephapirin, cephradine, ciprofloxacin, clarithromycin, clindamycin, colistin, dalbavancin, dalfopristin, daptomycin, doripenem, doxycycline, ertapenem, eravacycline, erythromycin, fosfomycin, gentamicin, imipenem, kanamycin, lefamulin, levofloxacin, linezolid, lincomycin,meropenem, metronidazole, minocycline, moxifloxacin, nalidixic acid, neomycin,nitrofurantoin, oritavancin, penicillin, piperacillin, polymyxin B, quinupristin, retapamulin, rifampicin, streptomycin, sulfacetamide, sulfadiazine, sulfamethizole, sulfamethoxazole, sulfasalazine, sulfisoxazole, teicoplanin, telavancin, tetracycline, tigecycline, tobramycin, trimethoprim, or vancomycin, or a combination thereof.

214. The pharmaceutically acceptable salt of any one of claims 124-203, wherein thepharmaceutical compound is an anticoagulant or a thrombolytic.

215. The pharmaceutically acceptable salt of claim 214, wherein the anticoagulant or thrombolytic comprises alteplase, argatroban, bivalirudin, fondaparinux, lepirudin,streptokinase, or urokinase, or a combination or two or more thereof.

216. The pharmaceutically acceptable salt of any one of claims 124-203, wherein the pharmaceutical compound is an antifungal.

217. The pharmaceutically acceptable salt of claim 216, wherein the antifungal comprises an azole antifungal.

218. The pharmaceutically acceptable salt of claim 216, wherein the antifungal comprises albendazole, clotrimazole, econazole, fluconazole, isavuconazole, itraconazole, ketoconazole, miconazole, posaconazole, tebuconazole, thiabendazole, or voriconazole, or a combination or two or more thereof.

219. The pharmaceutically acceptable salt of claim 216, wherein the antifungal is amphotericin B, anidulafungin, caspofungin, flucytosine, micafungin, natamycin, or voriconazole, or a combination or two or more thereof.

220. The pharmaceutically acceptable salt of any one of claims 124-203, wherein the pharmaceutical compound is an antineoplastic.

221. The pharmaceutically acceptable salt of claim 220, wherein the antineoplastic is afatinib, alectinib, alisertib, axitinib, bosutinib, cabozantinib, canertinib, carfilzomib, cediranib, ceritinib, cimicoxib, cobimetinib, dabrafenib, darapladib, dasatinib, delcasertib, dovitinib, erlotinib,Attorney Docket No.: 53160-716.601 etoricoxib, filanesib, glesatinib, ibrutinib, idelalisib, imatinib, ispinesib, ixazomib, lapatinib,lenvatinib, linsitinib, lonafarnib, masitinib, motesanib, nilotinib, nintedanib, odanacatib,olaparib, onalespib, osimertinib, palbociclib, pazopanib, pelitinib, ponatinib, regorafenib, rilapladib, ruxolitinib, seliciclib, sonidegib, sorafenib, sunitinib, tandutinib, tipifarnib, tofacitinib, vandetanib, varlitinib, varlitinib, vatalanib, veliparib, vemurafenib, vismodegib, or a combination or two or more thereof.

222. The pharmaceutically acceptable salt of any one of claims 124-203, wherein the pharmaceutical compound is an antiviral.

223. The pharmaceutically acceptable salt of claim 222, wherein the antiviral comprises abacavir, acyclovir, adefovir, amantadine, amprenavir, atazanavir, bictegravir, cidofovir, darunavir, dasabuvir, delavirdine, didanosine, dolutegravir, efavirenz, elvitegravir, emtricitabine, enfuvirtide, entecavir, famciclovir, foscarnet, ganciclovir, grazoprevir, imiquimod, indinavir, lamivudine, laninamivir, ledipasvir, lopinavir, maraviroc, nelfinavir, nevirapine, ombitasvir, oseltamivir, paritaprevir, penciclovir, peramivir, plerixafor, podofilox, raltegravir, ribavirin, rilpivirine, ritonavir, saquinavir, sofosbuvir, stavudine, tenofovir, tipranavir, trifluridine, valaciclovir, valganciclovir, zanamivir, or zidovudine, or a combination thereof.

224. The pharmaceutically acceptable salt of any one of claims 124-203, wherein the pharmaceutical compound comprises a cardiovascular medication.

225. The pharmaceutically acceptable salt of claim 224, wherein the cardiovascular medication comprises Bretylium, Dobutamine, Dopexamine, Epoprostenol, Esmolol, Iloprost, Nesiritide, Nitroglycerin, Norepinephrine, or Phenylephrine, or a combination or two or more thereof.

226. The pharmaceutically acceptable salt of any one of claims 124-203, wherein thepharmaceutical compound comprises a central nervous system depressant.

227. The pharmaceutically acceptable salt of claim 226, wherein the central nervous system depressant comprises alprazolam, chlordiazepoxide, clonazepam, diazepam, dexmedetomidine, dextromethorphan, flurazepam, gabapentin, ketamine, lorazepam, midazolam, oxazepam,propofol, temazepam, or triazolam, or a combination or two or more thereof.

228. The pharmaceutically acceptable salt of any one of claims 124-203, wherein thepharmaceutical compound comprises a central nervous system stimulant.

229. The pharmaceutically acceptable salt of claim 228, wherein the central nervous system stimulant comprises amphetamine, cocaine, dexmethylphenidate, dextroamphetamine, ephedrine, lisdexamfetamine, methamphetamine, methylphenidate, modafinil, phenylephrine, pseudoephedrine, or sibutramine, or a combination or two or more thereof.Attorney Docket No.: 53160-716.601 230. The pharmaceutically acceptable salt of any one of claims 124-203, wherein the pharmaceutical compound comprises a local anesthetic.

231. The pharmaceutically acceptable salt of claim 230, wherein the local anesthetic comprises articaine, benzocaine, bupivacaine, chloroprocaine, cocaine, dibucaine, etidocaine, levobupivacaine, lidocaine, mepivacaine, prilocaine, procaine, proparacaine, ropivacaine, or tetracaine, or a combination thereof.

232. The pharmaceutically acceptable salt of any one of claims 124-203, wherein the pharmaceutical compound comprises an anti-nausea medicine.

233. The pharmaceutically acceptable salt of claim 232, wherein the anti-nausea medicine comprises dolasetron, granisetron, ondansetron, or palonosetron, or a combination thereof.

234. The pharmaceutically acceptable salt of any one of claims 124-203, wherein the pharmaceutical compound is an anti-migraine.

235. The pharmaceutically acceptable salt of claim 234, wherein the anti-migraine comprises almotriptan, avitriptan, donitriptan, eletriptan, frovatriptan, lasmiditan, naratriptan, rizatriptan, sumatriptan, or zolmitriptan, or a combination thereof.

236. The pharmaceutically acceptable salt of any one of claims 124-203, wherein the pharmaceutical compound comprises an anti-Parkinson’s medicine.

237. The pharmaceutically acceptable salt of claim 236, wherein the anti-Parkinson’s medicine comprises amantadine, apomorphine, benztropine, benserazide, bromocriptine, cabergoline, carbidopa, entacapone, foscarbidopa, foslevodopa, levodopa, melvodopa, pramipexole, rasagiline, ropinirole, rotigotine, safinamide, selegiline, tolcapone, or trihexyphenidyl, or a combination thereof.

238. The pharmaceutically acceptable salt of any one of claims 124-203, wherein the pharmaceutical compound comprises an antihistamine.

239. The pharmaceutically acceptable salt of claim 238, wherein the antihistamine comprises acrivastine, brompheniramine, cetirizine, chlorpheniramine, clemastine, cyproheptadine, desloratadine, dexchlorpheniramine, diphenhydramine, doxylamine, fexofenadine, hydroxyzine, levocetirizine, loratadine, meclizine, promethazine, or tripelennamine, or a combination thereof.

240. The pharmaceutically acceptable salt of any one of claims 124-203, wherein the pharmaceutical compound comprises an H2 histamine receptor blocker.

241. The pharmaceutically acceptable salt of claim 240, wherein the H2 histamine receptor blocker is cimetidine, famotidine, nizatidine, or ranitidine, or a combination thereof.

242. The pharmaceutically acceptable salt of any one of claims 124-203, wherein thepharmaceutical compound comprises an opioid.Attorney Docket No.: 53160-716.601 243. The pharmaceutically acceptable salt of claim 242, wherein the opioid comprises buprenorphine, butorphanol, codeine, fentanyl, heroin, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, naloxone, naltrexone, nalmefene, oxycodone, oxymorphone, pentazocine, sufentanil, tapentadol, or tramadol, or a combination or two or more thereof.

244. The pharmaceutically acceptable salt of any one of claims 124-203, wherein the pharmaceutical compound is a tyrosine kinase inhibitor.

245. The pharmaceutically acceptable salt of claim 244, wherein the tyrosine kinase inhibitor comprises bosutinib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, ponatinib, sorafenib, or sunitinib or two or more thereof.

246. The pharmaceutically acceptable salt of any one of claims 124-203, wherein the pharmaceutical compound comprises amifampridine, amifostine, aminocaproic acid, argatroban, asenapine, atropine, bivalirudin, cisatracurium, deferoxamine, desmopressin, gabapentin, lurasidone, milrinone, nicotine, octreotide, pregabalin, rocuronium, terbutaline, tirofiban, tranexamic acid, vecuronium, nepafenac, or any combination thereof.

247. The pharmaceutical composition of any one of claims 1-123, wherein at least one of the acidic functional groups is complexed with a cation comprising Na+, K+, Mg2+, Ca2+, H3O+, or a combination thereof.

248. The pharmaceutically acceptable salt of any one of claims 124-246, wherein at least one of the acidic functional groups is complexed with a cation comprising Na+, K+, Mg2+, Ca2+, H3O+, or a combination thereof.

249. A method of preparing a pharmaceutical composition, comprising combining in a suitable liquid medium: a) a free base form of a pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof, wherein the pharmaceutical compound comprises at least one basic nitrogen atom and a pKa of at least 1; and b) a free acid form of a complexing agent comprising at least one acidic functional group, wherein the molar ratio of the complexing agent to the pharmaceutical compound is from about 1:1 to about 1:

10.

250. A method of treating a disease or disorder comprising administering a pharmaceutical composition of any one of claims 1-123, 247 or a pharmaceutically acceptable salt of claims 124-246, 248.

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