Complex salt formulations of pharmaceutical compounds with low stoichiometric ratios

Abstract

Provided herein are pharmaceutical formulations and pharmaceutical compound salts that utilize complexing agents as counterions. Such formulations and salts can be used to treat a variety of diseases and conditions. Also provided herein are methods of treatment using the pharmaceutical compounds, pharmaceutical compositions, and pharmaceutically acceptable salts of the present disclosure.

Description

[0001] Cross-references to other applications This application claims the benefit of U.S. Provisional Application No. 63 / 602,269, filed November 22, 2023, the entire contents of which are incorporated herein by reference. Background Technology

[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) can be used for a variety of pharmaceutical purposes. These compounds can be used to treat conditions such as Parkinson's disease, migraines, cancer, viral infections, bacterial infections, autoimmune diseases, inflammatory diseases, opioid dependence, pain, or other conditions. However, compounds may have many physicochemical properties that make it difficult to formulate suitable agents for widespread use as pharmaceuticals, including the presence of basic amines, limited solubility, hydrophobicity, and inherent ionic functional groups. Summary of the Invention

[0003] In some aspects, this document provides pharmaceutical compositions comprising: (i) a pharmaceutical compound or an enantiomer, mixture of enantiomers or 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 including acidic groups that act as counterions of the protonated nitrogen atom of the pharmaceutical compound, wherein the molar ratio of the complexing agent to the pharmaceutical compound in the pharmaceutical composition is about 1:1 to about 1:10. In some aspects, this document provides pharmaceutical compositions comprising: (i) a pharmaceutical compound, its enantiomers or isotopic variants, 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 including acidic groups that act as counterions of the protonated nitrogen atom of the pharmaceutical compound, wherein the molar ratio of the complexing agent to the pharmaceutical compound in the pharmaceutical composition is from about 1:1 to about 1:10. In some aspects, this document provides pharmaceutical compositions comprising: (i) a pharmaceutical compound or an enantiomer thereof, 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, said plurality of acidic functional groups including acidic groups acting as counterions of the protonated nitrogen atom of the pharmaceutical compound, wherein the molar ratio of the complexing agent to the pharmaceutical compound in the pharmaceutical composition is about 1:1 to about 1:10. In some aspects, this document provides pharmaceutical compositions comprising: (i) a pharmaceutical compound or an enantiomer thereof,The pharmaceutical composition comprises an enantiomer mixture or isotopic variant, wherein the pharmaceutical compound contains 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, the plurality of acidic functional groups including acidic groups that act as counterions to the protonated nitrogen atom of the pharmaceutical compound, wherein the molar ratio of the complexing agent to the pharmaceutical compound in the pharmaceutical composition is 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 sulfobutyl ether-β-cyclodextrin (SBEBCD). In some embodiments, the pKa of the pharmaceutical compound is at least 1. In some embodiments, the pKa of the pharmaceutical compound is about 1 to about 7.5. In some embodiments, the pKa of the pharmaceutical compound is about 1 to about 5. In some embodiments, the pKa of the pharmaceutical compound is from about 7.5 to about 13. In some embodiments, the pharmaceutical compound includes 5'-deoxyribonucleoside, 6,7-benzomorphine, ajmaline-sarpagine alkaloid, organoalkaline earth metal compounds, amaryllidaceae alkaloids, anthracene, anthracene rings, aporphine, azaspirodecane, azacycloheptane, azobenzene, azole, azoidine, azoline, benzazazepine, benzene, and substituted benzene. and substituted), benzimidazole ribonucleoside and ribonucleotide, benzimidazole, benzocycloheptapyridine, benzodiazepine, benzodioxane, benzodioxole, benzofuran, benzopyran, benzopyrazole, benzothiazepine, benzothiazine, benzothiazolium, benzothiazolium, benzothiophene, benzothiaran, benzotriazole, benzoxadiazole, benzoxazepine, benzoxazine, benzoxepine, biotin, camptothecin, carboxylic acid, Cephalotaxus alkaloid, cinchona alkaloid alkaloids, cinnamic acid, coumarin, cycloheptaphene, condensed phenolic acids and condensed phenolic acid cyclic ethers, diarylheptanoids, diazanaphthalene, diazacyclohexane, diazine, dibenzocycloheptenene, dioxane, epoxides, ergoline, fatty acyl groups, flavin nucleotides,Flavonoids, fluorene, furans, furanopyrans, glycerophospholipids, other homogeneous nonmetallic compounds, hydroxy acids, ibogan-type alkaloids, imidazodiazepines, imidazoribonucleosides and ribonucleotides, imidazopyridines, imidazopyrimidines, imidazothiazoles, indene, indene and isoindene, indole, indolizidine, isocoumaranthene, isoindole, isoquinoline, lactams, linear 1,3-diarylpropane, lupin alkaloids Alkaloids, macrolactams, macrolide lactams, macrolide morphine, tetraphenyl, naphthalene, naphthofuran, naphthopyran, nucleosides and nucleotide analogs, organic carbonic acid, organophosphorus, organophosphonic acid, organic sulfonic acid, organic nitrogen compounds, organic oxygen compounds, organothiophosphorus compounds, oxazine, peptide analogs, phenanthrene, phenanthrene-rholine, phenol esters, phenol ethers, phenol, phenylpropionic acid, phthaloylisoquinoline, piperazine-azahexaenoic acid, piperidine, polypeptides, isopentenyl alcohol lipids, pteridine, purine nucleosides, purine nucleotides, pyridine Zolopyridine, pyrazolopyrimidine, pyridine, pyridopyrimidine, pyrimidine nucleoside, pyrrole, pyrrolidine, pyrrolopyrazine, pyrrolopyridine, pyrrolopyrimidine, quinoline, steroids and steroids, piracetam, tetracycline, tetrahydroisoquinoline, naphthiazine, thienodiazepine, thienopyridine, thienothiazine, thiochromene, thioether, thiol, thiophene, transition metal salts, triazacyclohexane, triazine, triazole ribonucleoside and ribonucleotide, triazolopyrimidine, triphenyl compounds, tropane alkaloids, vinca alkaloids, yohimbine alkaloids, or derivatives thereof or combinations thereof. In some embodiments, the pKa of the pharmaceutical compound is from about 1 to about 2. In some embodiments, the pharmaceutical compound includes 1,4-benzodiazepine, amine, amino acid, peptide, androstened steroid, benzenesulfonamide, benzoic acid, benzophenone, benzothiadiazine, biphenyl, carboxylic acid derivative, phenolic peptide, diphenylmethane, ether, halobenzene, isoindoline, nitrogen mustard compound, nitroquinoline, purine 2'-deoxyribonucleoside, purine, pyrazole, pyrimidine or derivatives thereof, retinoids, substituted pyrroles or combinations thereof. In some implementations, the pharmaceutical compounds include apadenoson, asunaprevir, azilsartan medoxomil, benzthiazide, bromfenac, candesartan cilexetil, carbazochrome, chlorambucil, chlorothiazide, cladribine, clofarabine, clonazepam, CVT-6883, CX516, dacarbazine, and diazoxide.Emodepside, fimasartan, flubendazole, flucytosine, fludiazepam, flunitrazepam, ganciclovir, gliclazide, glisoxepide, grazoprevir, guanosine, ibudilast, ibuproxam, iocetamicacid, iopamidol, iopanoic acid acid), isatoribine, ixazomib, MB-07803, nateglinide, nepafenac, OPC-51803, pleconaril, pomalidomide, pralnacasan, pyrvinium, regadenoson, rimonabant, selexipag, simeprevir, sulfonamide Sulfadimethoxine, sulfamerazine, sulfameter, sulfamethadiazole, sulfamethoxazole, sulfametopyrazine, sulfamoxole, taranabant, tazarotene, tiopronin, tolazamide, tramidil, uracil mustard, or combinations thereof. In some embodiments, the pKa of the drug compound is about 2 to about 3. In some embodiments, the pharmaceutical compound includes azobenzene, azole, benzodiazepine, benzene, benzodiazepine, benzothiazine, benzothiazolium, carboxylic acid, phenolic acid, diazonium, diazine, imidazopyrimidine, indole, isoindole, lactam, macrolide naphthalene, nucleoside and nucleotide analog, organooxide, piperidine, isopentenyl alcohol lipid, pteridine, purine nucleoside, purine nucleotide, pyrazolopyrimidine, pyridine, pyrimidine nucleoside, pyrrolopyridine, quinoline, steroid, thienodiazepine, triazine, triazolopyrimidine, or combinations thereof. In some embodiments, the pharmaceutical compound includes 1,4-benzodiazepine, amino acids or peptides, aminotriazine, androstened steroids, acetanilide, aniline and substituted aniline,Benzoazapyridines, benzenesulfonamides, benzenesulfonyl compounds, benzodiazepines, benzoic acid and its derivatives, β-lactams, biphenyls and their derivatives, carbazoles, diphenyl ethers, diphenylmethanes, epothilosine estradiols, ethers, halobenzenes, isoindoline, milbemycin, monoterpenoids, nitroquinolines and their derivatives, oxosteroids, phenoxyacetic acid derivatives, phenylbutanylamine, phenylcarbamates, benzylamine, phenylpropane, phenylquinoline, pterin and its derivatives, purine 2',3'-dideoxyribonucleoside, purine ribonucleotides, purines and their derivatives, pyrazoles, pyrazolo[3,4-d]pyrimidines, pyridine carboxylic acids and their derivatives, pyrimidines and their derivatives, sulfonylaniline or combinations thereof. In some implementations, the pharmaceutical compounds include acyclovir, adipiplon, alisertib, allopurinol, ambrisentan, amelubant, aminobenzoic acid, aminopterin, aminosalicylic acid, amprenavir, anastrozole, arsanilic acid, asoprisnil, benzocaine, BMS-488043, becanavir, bromazepam, bumetanide, butamben, cangrelor, cefixime, cefpiramide, and chromium pyridinecarboxylate. Picolinate, cidofovir, ciluprevir, cinalukast, clazosentan, clotiazepam, cloxazolam, dabrafenib, dapsone, darunavir, delorazepam, diazepam, didanosine, dutasteride, edotecarin, efonidipine, elacytarabine, entecavir, epirizoole, epothilone D, finasteride, fluconazole, flumetamol (18F), folic acid, and 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, Motexafingadolinium, Motexafin lutetium, moxidectin, naxifylline, nitrazepam, nitroxoline, olaparib, ombitasvir, OT-551, papimate O, paritaprevir, patupilone, penciclovir, phenyl aminosalicylate, PPL-100, pralatrexate, quazepam, ravuconazole, regorafenib, regrelor, ritonavir, roflumilast, roxadustat, silver sulfadiazine sulfadiazine, sorafenib, stanozolol, sulfabenzamide, sulfacetamide, sulfacytine, sulfadiazine, sulfadoxine, sulfamerazine, sulfamethazine, sulfanilamide, sulfaphenazole, sulfapyridineSulfasalazine, sulfathiazole, sulfisoxazole, talnetant, tasosartan, technetium[99mTc]disofenin, technetium[99mTc]mebrofenin, tezosentan, ticagrelor, tirapazamine, troxacitabine, trypan blue, voriconazole, or combinations thereof. In some embodiments, the pKa of the drug compound is from about 3 to about 4. In some embodiments, the pharmaceutical compound includes 1,4-benzodiazepine, amino acids, peptides, acetanilide, aniline and substituted aniline, anisole, aryl thioether, benzodiazepine, benzofuranone, benzoic acid and its derivatives, benzophenone, β-lactam, biphenyl and its derivatives, bipyridine and oligopyridine, carbodiimide, diphenyl ether, diphenylmethane, epothilone estradiol, ether, haloquinoline, hexacarboxylic acid and its derivatives, imidazole, isoindole, milbemycin, morpholine, phenoxyacetic acid derivatives, benzylamine, phenylpyridine, piperazine, pterin and its derivatives, purine 2',3'-dideoxyribonucleoside, purine and its derivatives, purine and its derivatives, pyrazine, pyrazole, pyridine carboxaldehyde, pyridine carboxylic acid and its derivatives, pyridine sulfonamide, pyridyltriazole, steroid ester, sulfonyl acetanilide, sulfinylbenzimidazole or combinations thereof. In some embodiments, the pharmaceutical compounds include adenosine, amiloride, aminobenzoic acid, aminophenazone, anagrelide, aprepitant, para-aminobenzoic acid, azathioprine, aztreonam, benzocaine, benzonatate, bisacodyl, bromazepam, brotizolam, bumetanide, butanene, and calcium cyanamide. (carbimide), cefepime, cefixime, cefmenoxime, cefotaxime, cefpodoxime, cefftizoxime, ceftriaxone, chloroxine, chromium pyridinecarboxate, clioquinol, dabigatran etexilate, dabrafenib, dexlansoprazole, dexrazoxane, diazepam,Desoxyinosine, diiodohydroxyquinoline, entecavir, etofibrate, etravirine, ezogabine, flumazenil, flumetafol (18F), indocyanine, inosine, inositol nicotinate, iopodic acid, irbesartan, isocarboxazid, isoniazid, itraconazole, ixaspirin, lansoprazole, leucovorin, levofolinic acid, levomefolic acid (The following are listed as unrelated terms and phrases: acid), rosiglitazone, losartan, lumacaftor, mazindol, mebendazole, mercaptopurine, methotrexate, metronidazole, montelukast, moxifloxacin, nelarabine, niacin, nicorandil, nicotinamide, norelgestromin, norgestimate, oxfendazole, pardimethicone, pantoprazole, penciclovir, perampanel, picosulfuric acid) acid), piroxicam, posaconazole, prazepam, procainemerethoxylline, pyridoxal, pyridoxal phosphate, riociguat, ritonavir, stanozolol, talniflumate, tasosartan, tenofovir disoproxil, thiabendazole, thonzonium, ticagrelor, tinidazole, thioguanine, topiroxostat, torasemide, triamterene, vemurafenib, vemurafenibVismodegib or combinations thereof. In some embodiments, the pKa of the pharmaceutical compound is about 4 to about 5. In some embodiments, the pharmaceutical compound includes 1,4-benzodiazepine, 1-ribosyl-imidazolium carbamate, 2-benzimidazolyl carbamate, 8-hydroxyquinoline, amine, amino acid, peptide, androstened steroid, acetanilide, aniline and substituted aniline, anthraquinone, aryl sulfide, benzodiazepine, benzoic acid and derivatives, β-lactam, biphenyl and derivatives, bipyridine and oligopyridine, bisphosphonate, carbonyl compound, diphenylmethane, ether, hexachlorocyclohexane, etc. Carboxylic acids and their derivatives, imidazoles, imidazoquinones, indolequinones, naphthidines, oxosteroids, phenethylamine, phenylbenzimidazole, phenylhydrazine, phenylpiperidine, phenylpyridine, phenylquinoline, pterin and its derivatives, purine ribonucleotides, purines and purine derivatives, pyrazolo[1,5-a]pyrimidine, pyridine carboxylic acids and their derivatives, pyridine sulfonamides, pyridoindole, quinoline carboxylic acids, styrene, sulfinylbenzimidazole, trifluoromethylbenzene, or combinations thereof. In some embodiments, the pharmaceutical compounds include azathioprine, abiraterone, acadesine, adenosine 5'-phosphorylsulfate, adenosine monophosphate, AICA ribonucleotides, albendazole, amfecloral, aminoglutethimide, and aminohippuric acid. Acid), Amrinone, Atazanavir, Aztreonam, Banoxantrone, Binodenoson, Diacetyl, Carfilzomib, Cefditoren, Cefepime, Cefotaxime, Cefotaxime, Cefpodoxime, Ceftazidime, Ceftibuten, Ceftriaxone, Coenzyme A, Dexlansoprazole, Ensulizole, Erlotinib, Esomeprazole, Estazolam, Etizolam, Etomidate, Etocoxib, Itravirine, Fiboflapon, Flavin Adenine dinucleotide, florbetaben (18F), florbetapir (18F), geldanamycin, gentian violet, hexocyclium, idelalisib.Impitapide, Indium In-111O-quinoline, Nicotinic Acid Inositol Ester, Iophobic Acid, Irbesartan, Lansoprazole, Levosimendan, Loratadine, Lornoxicam, Losartan, LX-2931, Methoxyamine, Metyrapone, Mifepristone, Milrinone, Minoxidil, Nalidixic Acid (acid), nicotinic acid, ocinaplon, omeprazole, OSI-930, oxibendazole, oxyquinoline, perampanel, piclidenoson, picosulfate, pitavastatin, porfiromycin, PX-12, pyridoxal, pyridoxal phosphate, rabeprazole, repaglinide, resiquimod, retaspimycin, ridogrel, riluzole, risedronate, riglitazone glitazone), rosoxacin, S-8510, sapropterin, tecadenoson, tenofovir disoproxil fumarate, tenoxicam, thiabendazole, torasemide, triazolam, tucidinostat, ulipristal, varlitinib, vatalanib, verteporfin, verubulin, vidarabine, vipadenant, vorapaxar, or combinations thereof. In some embodiments, the pKa of the drug compound is about 5 to about 6. In some embodiments, the pharmaceutical compounds include 1,4-benzodiazepine, 1-ribosyl-imidazolium carbamate, 2-benzimidazolyl carbamate, 8-hydroxyquinoline, amine, amino acid, peptide, androstened steroid, acetanilide, aniline and substituted aniline, anthraquinone, aryl sulfide, benzodiazepine, benzoic acid, β-lactam, biphenyl, bipyridine and oligopyridine, bisphosphonates, diphenylmethane, ether, hexacarboxylic acid, imidazole, imidazoquinoline, indolequinone, naphthidine, oxosteroid, phenethylamine, phenylbenzimidazole, phenylhydrazine, phenylpiperidine, phenylpyridine, phenylquinoline, pterin, purine ribonucleotide, purine and purine derivatives, pyrazolo[1,5-a]pyrimidine, pyridine carboxaldehyde,Pyridine carboxylic acid, pyridine sulfonamide, pyridoindole, quinoline carboxylic acid, styrene, sulfinylbenzimidazole, trifluoromethylbenzene or its derivatives or combinations thereof. In some embodiments, the pharmaceutical compound includes 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, 5-methyltetrahydrofolate, abacavir, adefovir dipivoxil, adenine, alprazolam, ALT-2074, amdoxovir, apimod, adenosine triphosphate, avanafil, axitinib, azelnidipine, benazepril, benzimidazole, bisisate, and biricodar dicitrate. dicitrate), Brilliant Green, cabozantinib, capravirine, carbidopa, cefapirin, cerivastatin, cilazapril, cisplatin, clevidipine, clonixin, clopidogrel, cocarboxylase, dapivirine, delamanid, dersalazine, dolasetron Setron, Elbasvir, Enalapril, Ethionamide, Etefoxine, Etozoline, Famciclovir, Felodipine, Floctafenine, Fominoben, Fosaprepitant, GTS-21, Hetacillin, Imidacloprid, Imiquimod, Incadronic acid, Indibulin, Isoselan blue, Iradipine, Kinetin, Lamotrigine, Leadipasvir, Linsitinib, Meclinertant, Mesalazine, Methenamine.Moexipril, morniflumate, NADH, nevirapine, nifedipine, niflumicacid, nimodipine, nisoldipine, nitrendipine, olmesartan, pazopanib, peldesine, perindopril, phenelzine, picoplatin, pinacidil, pioglitazone, pipecuronium, pradefovir mesylate mesylate, prasugrel, prinomastat, procarbazine, pyridoxine, quinapril, ramipril, rilpivirine, rostaporfin, ruxolitinib, seliciclib, sildenafil, sonidegib, spirapril, stannsoporfin, talmapimod, taribavirin, temocapril, temoporfin, tenofovir alafenamide The drug compound may contain alafenamide, thiamine, trandolapril, tropicamide, velpatasvir, ximelagatran, zinc picolinate, zolpidem, or combinations thereof. In some embodiments, the pKa of the drug compound is about 6 to about 7. In some embodiments, the pharmaceutical compounds include 1,4-benzodiazepine, 1-ribosyl-imidazolium carbamate, 2-benzimidazolyl carbamate, 8-hydroxyquinoline, amine, amino acid, peptide, androstened steroid, acetanilide, aniline and substituted aniline, anthraquinone, aryl sulfide, benzodiazepine, benzoic acid, β-lactam, biphenyl, bipyridine and oligopyridine, bisphosphonates, carbonyl compounds, diphenylmethane, ether, hexacarboxylic acid, imidazole, imidazoquinone, indolequinone, naphthidine, oxosteroid, phenethylamine, phenylbenzimidazole, phenylhydrazine, etc.Phenylpiperidine, phenylpyridine, phenylquinoline, pterin, purine ribonucleotide, purine and purine derivatives, pyrazolo[1,5-a]pyrimidine, pyridine carboxylic acid, pyridine sulfonamide, pyridoindole, quinoline carboxylic acid, styrene, sulfinylbenzimidazole, trifluoromethylbenzene or its derivatives or combinations thereof. In some embodiments, the pharmaceutical compounds include 2-amino-1-methyl-6-phenylimidozolo(4,5-b)pyridine, 5-methyltetrahydrofolate, abacavir, adefovir dipivoxil, adenine, alprazolam, ALT-2074, amdoxavir, apimod, avanafil, azledipine, benazepril, benzimidazole, bisacodyl, bicoxadazole dicitrate, Brilliant Green, capvirline, carbidopa, cerivastatin, cilazapril, cisplatin, clovidipine, clonidine, clopidogrel, cocarboxylase, dapoxetine, delamani, desarazine, dolasetron, elbasvir, enalapril, etofosine, etorazoline, famciclovir, felodipine, flavoxine, and flavoxine. Fenipin, Fominoben, Fosapitan, GTS-21, Hetacillin, Imidacloprid, Imiquimod, Incadronic acid, Indebulin, Isoostatin, Iradipine, Kinetin, Lamotrigine, Leadipasvir, Melanathan, Mesalazine, Urotropine, Moxipril, Mornifluoxetine, Nevirapine, Nifedipine, Nifluoxetine, Nimodipine, Nisodipine, Nifedipine, Olmesartan, Pazopanib, Pedesine, Perindopril, Phenylezil, Pyrapoplatin, Pinafenadil, Pioglitazone, Piperacillin, Pradefovir Mesylate, Prasugrel, Prinstat, Procarbazine, Pyridoxine, Quinapril, Ramipril, Rilpivirine, Ropepoxetine, Ruxolitinib, Celicillin, Sildenafil Non-Sonidazole, Ropril, Sipofen, Tapimod, Talivirine, Temopril, Temopofen, Tenofovir Acetonide, Thiamine, Qundopril, Topiramate, Velpatasvir, Cimetidine, Zinc Pyridinecarboxate, Zolpidem, Acarbose, Ajmaline, Alcaftadine, Alfentanil, Alfuzosin, Almitrine, Amisulpride, Amoxicillin, Ampicillin Amrubicin, antrafenine, aripiprazole, asenapine, atipamezole, azaperone, bacampicillin, cefaclor, cefadroxil, cefdinir, cefprozil, cefalexin, cephaloglycin.The following medications are listed: chlordiazepoxide, clozapine, dalfopristin, dasatinib, diethylpropion, domperidone, dorzolamide, doxapram, doxazosin, drotaverine, efinaconazole, eprazoline, flavoxate, flibanserin, flupirtine, imidafenacin, indinavir, ketamine, ketotifen, lapatinib, loxapine, mepivacaine, methacycline, and misosine. The pharmaceutical compound may contain oxonidine, nefazodone, oftasceine, olanzapine, ondansetron, phendimetrazine, pivampicillin, pramocaine, prazosin, quetiapine, ranolazine, rupatadine, setiptiline, terazosin, tetrabenazine, ticlopidine, tizanidine, tofacitinib, trazodone, trimethoprim, valaciclovir, valganciclovir, ziprasidone, or combinations thereof. In some embodiments, the pKa of the pharmaceutical compound is about 7 to about 8. In some embodiments, the pharmaceutical compounds include amaryl-snake root alkaloids, 1,4-benzodiazepines, 2,3,5-trisubstituted thiophenes, alcohols and polyols, amines, amino acids or peptides, acetoanilides, anisoles, benzodiazepines, benzo[a]arene, benzene, benzimazole, benzocycloheptapyridine, benzodiazepines, benzodiazine, benzofuran, benzoic acid, benzothiadiazole, benzothiazole, benzo[a]thiazole, benzo[a]triazole, benzo[a]oxazine, benzo[a]oxazine, benzylamine, benzylisoquinoline, benzylpiperidine,β-lactams, biphenyls, carbazoles, carbohydrates, carbonyl compounds, carboxylic acids, cycloheptaphenes, diarylheptane compounds, diazanaphthalenes, diazacyclohexanes, diazines, dibenzocycloheptenene, dibenzodiazepines, dibenzothioazepines, dibenzooxazines, dibenzooxazines, diphenylmethane, ergolin, flavonoids, flavonoids, halobenzenes, heteropeptides, hydropyridine, indene, indole, indoline, isoquinoline, isoquinolinones, lactams, linear diarylheptane compounds, lysergic acid, macrolactams, macrolide lactams, monoterpenoids, morpholine. n-Acylpiperidine, n-alkylindole, tetraphenyl, naphthopyranone, naphthopyran, n-phenylurea, organic nitrogen compounds, organic oxygen compounds, oxazine, pentacarboxylic acid, peptide mimics, phenanthrene, phenethylamine, phenol ether, benzylamine, phenylpiperidine, phenylhyoscyamine, piperazine, piperidine carboxylic acid, piperidine, polypeptides, isopentenol lipids, pyridazine and its derivatives, pyridine, pyrimidine 2'-deoxyribonucleoside, pyrimidine nucleoside, pyrimidine, quinoline carboxylic acid, quinoline, steroid esters, steroids, tetrabenzoquinone, tetracycline, tetrahydroisoquinoline, thienopyridine, thiophene, hyoscyamine alkaloids, xylene, yohimbine alkaloids or their derivatives or combinations thereof. In some implementations, the pharmaceutical compounds include acarbose, amorin, acalacatta, alfentanil, alfuzosin, alizapride, amitriazine, almorexant, hexamethylmelamine, altropane, alvocidib, amdinocillin, aminolevulinic acid, amisulpride, amoxicillin, ambicillin, amrubicin, triamcinolone, aripiprazole, asenapine, atemetazole, AV-412, azapirolone, azatadine, bamectin, barnidipine, benidipine, bifeprunox, bleomycin, blonanserin, and blannicline. Radanicline, bifentanil, bupivacaine, buspirone, cariporide, cariprazine, caspopitant, cathinone, cefaclor, cefadroxil, cefdinir, cefprozil, cefradine, cefalexin, cefotaxime, cethromycin, cetirizine, chlorcyclizine, chlortetracycline, cilansetron, clozapine, dapoxetine, dapiprazole.Dasatinib, deserpidine, diethylamine benzophenone, domperidone, dazozoline, dovitinib, doxaprim, doxazosin, doxycycline, drotaverine, edonerpic, elfluconazole, elsamitrucin, eluxadoline, enalaprilat, enzastaurin, edaprazone, ergonovine, ergotamine, EVT-101, ezatiostat, facinicline, fenproporex, finafloxacin, flavoxetine, flubancerine, flunarizine unarizine, flupiridin, hexaminolevulinate, hydroxyzine, iclaprim, iloperidone, midazoline, indinavir, josamycin, ketamine, ketotifen, lapatinib, larazotide, lesopitron, levobupivacaine, levocetirizine, lidocaine, linaclotide, lofexidine, loracarbef, lorpiprazole, loxapine, lysergic acid diethylamide acid diethylamide), manidipine, mepiprazole, malbifocaine, methoxytetracycline, methyl aminolevulinate, methyl ergonovine, mesysergide, miglitol, motesanib, mosonidin, naloxone, naluzotan, nefazodone, netupitant, olanzapine, onalespib, ondansetron, oxytetracycline, palonosetron, perospirone, benzotriazine, phenoxybenzamine, pirenzepine, pivmecillinam, pizothifen, promocaine, prazosin.priralfinamide, prx-08066, pyrimethamine, quetiapine, RAF-265, raloxifene, ranolazine, reboxetine, remifentanil, rescinnamine, reserpine, rifampicin, rifapentine, rocuronium, ropivacaine, rupatadine, safinamide, saxagliptin, spretiline, SNX-5422, solitromycin, sufugolix, SUVN-502, talactoferrin Alpha), telithromycin, terazosin, buphenazine, ticlopidine, tipifanib, tizanidine, tofacitinib, trabectedin, trazodone, trimethoprim, trimetrexate, tymazoline, valacyclovir, valganciclovir, valomaciclovir, valtorcitabine, venetoclax, voglibose, yohimbine, ziprasidone, zosuquidar, or combinations thereof. In some embodiments, the pKa of the drug compound is about 8 to about 9. In some embodiments, the pharmaceutical compounds include 1-benzopyran, 1-benzothiaran, 1-phenyltetrahydroisoquinoline, alcohols, polyols, amines, amino acids, peptides, aminoquinoline and derivatives, androstened steroids, acetanilide, anisole, aryl sulfides, hydroquinone, benzenesulfonamide, benzo-1,4-dioxane, benzodiazepine, benzoic acid and derivatives, benzoquinoline, benzylamine, benzyl ether, benzylpiperidine, β-lactam, biphenyl and derivatives, carbazole, carbohydrates and carbohydrate conjugates, carbonyl compounds, carboxylic acid derivatives, phenolic peptides, and dibenzo[a]azine. Hybrids, dibenzothiohexane, dibenzooxynitrogenate, diphenylacetonitrile, diphenylfuran, diphenylmethane, ethers, fatty acids and conjugates, fentanyl, snowflake amine type Amaryllidacetic alkaloids, halobenzenes, hydrogenated pyridine, imidazoline, indazole, indole, indoloquinoline, isoquinolinones and derivatives, isoxazoline, lysergic acid and derivatives, methoxybenzene, monoterpenoids, morpholine, n-alkylindole, naphthidine, oxadiazole, pentacarboxylic acid and derivatives, phenethylamine, phenothiazine, phenothiazine, phenoxy compounds, benzylamine, phenylnaphthalene, phenylpiperidine, phenylpropane, phenylpyridinePhenylpyrrolidine, phenylquinoline, piperazine, piperidine carboxylic acid and its derivatives, purines and purine derivatives, pyrimidines and pyrimidine derivatives, pyrrolylpyridine, quinoline carboxamide, quinoline carboxylic acid, styrene, substituted pyrroles, sulfonylaniline, tetracarboxylic acid and its derivatives, thiazoles, thiophene carboxylic acid and its derivatives, trifluoromethylbenzene, xylene or its derivatives or combinations thereof. In some embodiments, the pharmaceutical compounds include aceprometazine, acetophenazine, aclarubicin, acrivastine, afatinib, afimoxifen, alanosine, amiodarone, amino-N-13, ammonium molybdate, amonafide, amorolfine, amoxapine, and acetaminophen. Amsacrine, amylocaine, anamorelin, anileridine, aprindore, aclonidine, articaine, azoxifene, asimadoline, aspartame, astemizole, atrasentan, azelastine, azimilide. Bedaquiline, benzylfentanyl, bosutinib, brexpiprazole, brimonidine, bromodiphenhydramine, buclizine, budiodarone, bupivacaine, bupropion, butyrfentanyl, caldaret, captopril odiame, carbinoxamine, carfentanil, carvedilol, cefminox, cefotiam, celgosivir, cevimeline, chlorcyclophosphamide, chloroprocaine, chloropyramine, chloramphenicol I-131, cinnarizine, ciprofloxacin, cisapride.Clarithromycin, clofedanol, clomocycline, clonidine, cloperastine, CNS-5161, cocaine, cyclopenicillin, cyclizine, cyclopentolate, cycloserine, cyproheptadine, darapladib, daunorubicin, DDP-225, demeclocycline, deramciclane, desvenlafaxine, dicyclomine, dihydroergotamine ihydroergotamine, diltiazem, dimenhydrinate, dimetotiazine, diphenhydramine, diphenoxylate, diphenylpyraline, dofetilide, donepezil, dotarizine, doxorubicin, doxylamine, droxidopa, d-serine, dyclonine, edetic acid acid), edivoxetine, elacridar, eletriptan, eliglustat, emedastine, enoxacin, eperisone, epinastine, adrenaline, epirubicin, erythromycin, ethoheptazine, famotidine, fasudil, fentanyl, flupentixol, fluphenazine, flurazepam, forodesine, friulimicin B B) Gaboxadol, gadooversetamide, galantamine, garenoxacin, gatifloxacin, and glesatinib.Glucosamine, glypromate, granisetron, grepafloxacin, haloperidol, hydrocodone, hydromorphone, idarubicin, imatinib, imolamine, indium pentetate (In-111), iroxanadine, isoaminile, isoprenaline, isothipendyl, isoxsup rine), istaroxime, itopride, ketobemidone, lasofoxifene, L-asparagine, 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, naloxego l), nebivolol, nelfinavir, nicardipine, nicergoline, nicotine, norepinephrine, norfloxacin, normethadone, ocaperidone, ohmefentanyl, orphenadrine, osimertinib, oxybubucaine, oxybutynin, oxycodone.oxyphencyclimine, palfuramidine, palbociclib, paliperidone, paliroden, pargyline, PBT-1033, pelitinib, penetate calcium trisodium, penetate zinc trisodium trisodium, pentostatin, perphenazine, pethidine, phenindamine, phenmetrazine, phenyltoloxamine, pimavanserin, pimozide, pipamperone, pipazethate, pipendoxifene, pipotiazine, pirlindole, ponatinib, PPI-1019, prilocaine, procaine, prochlorperazine, proflavine, proparacaine, and properciazine. e) 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.Salfloxacin, sarizotan, selegiline, serine, sertindole, sincalide, sitagliptin, solifenacin, sparfloxacin, spinosad, sufentanil, sulpiride, tacrine, talabostat, tamoxifen ), tariquidar, technetium TC-99M tegaserod, terbinafine, terconazole, tetracaine, tetracycline, tegaserod, thioproperazine, thioridazine, thiothixene, thonzylamine, tianeptine, tigecycline cline, tocainide, tolperisone, toremifene, trifluoperazine, trimebutine, trimethobenzamide, tripelennamine, triprolidine, tromethamine, tubocurarine, udenafil, vanoxerine, velipanib ( veliparib, venlafaxine, vicriviroc, vilazodone, viloxazine, vinblastine, vincristine, vindesine, vinorelbine, voacamine, vortioxetine, xaliproden, xanthinol, zanapezil, zotepine, zuclopenthixol, α-methylfentanyl, α-methylthiofentanylβ-hydroxythiofentanyl or combinations thereof. In some embodiments, the pKa of the pharmaceutical compound is about 9 to about 10. In some embodiments, the pharmaceutical compounds include 1-benzopyran, 1-benzothiaran, 1-hydroxy-4-unsubstituted benzene compounds, 4-quinoline methanol, 5'-deoxy-5'-thionucleoside, amines, amino acids, peptides, aminophenyl ethers, aminoquinoline, acetanilide, anisole, anthraquinones, hydroquinone, benzyl sulfonamide, benzo-1,4-dioxane, benzodiazepine, benzoic acid, benzyl nitrile, benzoquinoline, benzoxazinone, benzoyl, benzyl alcohol, benzyl ether, benzylpiperidine, β-lactam, biphenyl, bisphosphonates, carbazole, carbohydrates and carbohydrate conjugates, cytisine, phenolic peptides, dibenzodiazepines, dibenzothiocyanates, dibenzooxazines, dicarboxylic acids, diphenylacetonitrile, diphenylmethane, diterpenoids, ethers, fentanyl, and glycerophosphates. Amino acids, halogenated benzenes, heteropeptides, hydrogenated pyridines, hydrogenated quinolines, hydroxypyridines, indazoles, indole carboxylic acids, indole, indoline, indoroquinoline, indole carboxylic acids, isoquinoline quinones, lysergic acid, methoxybenzene, naphthidine, nitrobenzene, nitroquinoline, organic sulfonic acids, pentacarboxylic acids, phenethylamine, pheniramine, phenothiazine, phenoxazine, phenoxy compounds, phenoxyacetic acid, phenylacetamide, phenylbutylamine, benzylamine, phenylpiperidine, phenylpropane, phenylhyoscyamine, piperazine, piperidine carboxylic acids, pregnane steroids, purines and purines, pyridinium, quinoline carboxylic acids, quinolones, steroid esters, styrene, substituted pyrroles, sulfonylaniline, tametraline, thiophene carboxylic acids, toluene, trifluoromethylbenzene, tryptamine, tyrosol, or derivatives thereof, or combinations thereof. In some embodiments, the pharmaceutical compounds include (3S)-3-methyl-D-aspartic acid, isocoxetine, 13-deoxydoxorubicin, 3-allyl fentanyl, 3-methylfentanyl, 4-phenylfentanyl, 7-hydroxystreakine, acebutolol, ademetionine, aldoxorubicin, and alendronic acid. Acid, alethine, alimemazine, aliskiren, amotriptan, alogliptin, alprenolol, ambroxol, amibegron, amikacin, amineptine, aminocandin, amitriptyline, amlodipine, amphotericin B, antazoline, apramycin, apririndine.Arbekacin, Arbutamine, Arimoclomol, Arotinolol, Atenolol, Atomoxetine, Atosiban, Atropine, Azithromycin, Bacitracin, Baclofen, Bambuterol, Bazedoxifene, Becatecar benfluorex, benzatropine, benzphetamine, benzzydamine, benzylpenicillin, bepotastine, bepridil, besifloxacin, betastine, betaxolol, betazole, bevantolol, bilastine, bimoclomol, bipiperidine Rieden, Bisoprolol, Bopindolol, Brasofensine, Bromhexine, Bromopride, Brompheniramine, Bufuralol, Bupranolol, Butenafine, Cabergoline, Canfosfamide, Carbocisteine, Carteolol, Caspofungin pofungin, 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, indigoline, dalbavancin, dapoxetine, daptomycin, darinaparsin, declopramide, demetriptyline, desloratadine, dexbrompheniramine, dexbrompheniramine maleate, dextromethorphan, dextromethorphan tromethorphan, dextropropoxyphene, dextrothyroxine, dezocine, difenoxin, dihydrocodeine, dimetacrine, dimetindene, diphenidol, dipivefrin, diprenorphine, diithromycin, D-methionine, dobutamine, dopamine, doripenem, dosulepin, doxepin, dronedarone, duloxetine, encainide, enclomiphene, ephedrine, epicept NP-1, eribulin, ertapenem, escitalopram, esmolol, ethambutol, ethopropazine, ethylmorphine, eticaine, etryptamine, fenoterol, fenspiride, ferrous glycinate, fexofenadine, filanesib, fingolimod, flecainide.Fluoxetine, fluspirilene, fluvoxamine, formoterol, framycetin, gabapentin, gadobenicacid, gadofosveset trisodium, gadopentetated meglumine, gadoteridol, gadoxetic acid (acid), gemifloxacin, glutamic acid, glutathione, glutathione disulfide, glycine, golotimod, gosogliptin, granisetron, halofuginone, heroin, heexetidine, hexylcaine, histamine, histidine, homatropine, huperzine A, huperzine B, hydroxyamphetamine, hydroxychloroquine, hyoscyamine, ibandronate, ifenprodil, imipramine, indacaterol, iodine fluoride Pan I-123, Irinotecan, Isoterine, Ispinesib, Ivabradine, K201, Kanamycin, Labetalol, L-Alanine, L-Aspartic Acid, L-Citrile Acid, L-Cysteine, L-Clercanidipine, Leukotriene C4, Levallorphan, Levaamlodipine, 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 glycine, mefloquine, melphalan, mereopenem, metataraminol, methadone, methadyl acetate, methionine, levomethoprazine, methoxamine, methyldopa, methylphenidate, metipranolol, metixene, metoclopramide, metoprolol, metyrosine, mexiletine, mibefradil, milnacipran, mirabegron, mitemcinal, mitoxantrone toxantrone, MN-305, morphine, moxifloxacin, nadolol, naftifine, nalmefene, naratriptan, naronapride, natamycin, nemonoxacin, netilmicin, nitroarginine, NPS-2143, NS-2359, nystatin, oglufanide, olodaterol, olopatadine, omacetaxel Mepesuccinate), OPC-28326, orciprenaline, osanetant, oseltamivir, oxamniquine, oxilofrine, oxitriptan, oxprenolol, pamidronate, paromomycin, paroxetine, penbutolol, penicillamine, pentoxyverine, pergolide, phenaridine, phenylindole.Phentolamine, phenylephrine, phenylpropanolamine, pholcodine, phosphatidylserine, piboserod, pindolol, piperazine, pirarubicin, pirbuterol, pixantrone, polaprezinc, pracinostat, practolol, procainamide ainamide, procaterol, procyclidine, promazine, promethazine, propafenone, propoxyphenenapsylate, propranolol, PRX-03140, pseudoephedrine, PX-478, quarfloxin, quinidine, quinidine barbiturate barbiturate, quinine, repinotan, retapamulin, ribostamycin, ritodrine, rizatriptan, ronacaleret, roxithromycin, salbutamol, salmeterol, saredutant, selenomethionine, seproxetine, serotonin, sertraline, sibutramine, silodosi n), siramesine, soraberon, sotalol, spectinomycin, spiramycin, sumanirole, sumatriptan, sunitinib, tamsulosin, tandutinib, tapentadol, TAS-108, taurine, tedisamil, telavancin, terbutaline, terfenadine, tesmilifeneTesofensine, tetrodotoxin, TG-100801, tiagabine, ticalopride, tilmicosin, timolol, tobramycin, topotecan, tramadol, tranylcypromine, triethylenetetramine, trifluoropromethazine, trihexyphenidyl, trimetazidine, trimethaprine Mipramine, trovafloxacin, tyramine, ubenimex, vancomycin, vandetanib, varenicline, vecuronium, verapamil, vernakalant, vigabatrin, vilanterol, vildagliptin, zolmitriptan, α-methylacetylfentanyl, α-methylfentanyl, β-methylfentanyl, or combinations thereof. In some embodiments, the pKa of the drug compound is from about 10 to about 13. In some embodiments, the pharmaceutical compounds include 2,6-dimethyl-3-benzo[a]arene, alkaline earth metal oxides, alkyl thiols, amines, amino acids, peptides, aminopyridine, aminoquinoline, hydroquinone, benzoic acid, benzo[a]quinoline, β-lactam, cholic acid, alcohols, biphenyl, bisphosphonates, carbazole, carbohydrates and carbohydrate conjugates, carboxylic acid derivatives, cyclohexylamine, phenolic peptides, dibenzo[a]azine, diphenylmethane, ethers, fatty acids and conjugates, guanidine, halobenzenes, heteropeptides, indole carboxylic acids, indole, indoline, monoterpenoids, n-arylamides, organic sulfonic acids, peptide-peptide hybrids, phenethylamine, fenilam, phenylbutylamine, benzylamine, phenylpiperidine, phenylpropane, phenylpropylamine, phenylpyridine, piperidine carboxylic acid, purines and purine derivatives, pyrazolylpyridine, pyrimidines and pyrimidine derivatives, tetracarboxylic acids, tryptamine, urea, xylene or its derivatives or combinations thereof. In some implementations, the pharmaceutical compounds include 2-iminobiotin, abarelix, ABT-510, afamelanotide, agmatine, alverine, alvimopan, amantadine, AMD-070, aifostine, aminocaproic acid, amodiaquine, and amphetamine.Anatibant, apomorphine, argatroban, arverapamil, atipremod, aviptadil, bedoradrine, benzoctamine, bethanidine, bicifadine, bivalirudin, brostallicin, buformin, buprenorphine, butorphanol, butriptyline, capreomycin, carbamide peroxide, ceftobiprole, ceritinib, cetrorelix, chlorhexidine, chloroquine, chlorpheniramine, cinacalcet, corticorelin ovinetriflutate, Cr665, creatine, crizotinib, cysteine, CZEN 002. Dalfampridine, darifenacin, debrisoquin, deferoxamine, degarelix, delcasertib, denibulin, desipramine, deslorelin, desmopressin, dexfenfluramine, dextroamphetamine, diethylnormethyl Spermine, dihydrostreptomycin, disopyramide, efornithine, envenom, etorphine, felypressin, fencamfamine, fenethylline, fenfluramine, fenoldopam, fesoterodine, fradifan, frovatriptan, fursultiamine, gadoteric acid, gadoterol, γ-aminobutyric acid,Ganirelix, gentamicin, gonadorelin, goserelin, guanadrel, guanethidine, halofantrine, hexoprenaline, histrelin, hydroxyproline, hydroxystilbamidine isethionate, ibutilide, icatibant, imipenem, indalpine, indecainide, iobenguane, iobenguane sulfate I-123, isometheptene, labradimil, L-aminocarnitine-succinyl-leucyl-arginine-diethylacetal, lanreotide, L-arginine, L-ornithine, levmetamfetamine, levocabastine, lisdexamfetamine Lisinopril, lixisenatide, L-lysine, lorcaserin, L-proline, magnesium oxide, maprotiline, maraviroc, mecamylamine, memantine, mefenamic acid, metformin, methamphetamine, midomafetamine, nafarelin, nalbuphine, naltrexone, naphazoline, neramexane, neridronic acid 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, pregab alin, prezatide, primaquine, progabide, proguanil, propylhexedrine, protriptyline, pyrantel, quinacrine, ramoplanin, rifaximin, rimantadine, rivanicline, romidepsin, ropinirole, rotigo Rotigotine, Saralasin, Satraplatin, Serotonin, SGS-742, Sitamaquine, SNS-032, Somatostatin, Spermine, SQ-109, Squalamine, Streptomycin, T131, Tafenoquine, Talotrexin, Tanespimycin, Tecastemizole, Tenocyclidine, Terlipressin (in), tesamorelin, tetracosactide, tetryzoline, tezampanel, tipiracil, tirofiban, tolazoline, tolterodine, taurine, tranexamic acid, triptorelin, ularitide, urea C-13, vapitadine, vintafolide, purpuric acid, WX-UK1Xylometazoline, zanamivir, or combinations thereof. In some embodiments, the pharmaceutical composition is a solid. In some embodiments, the pKa of the pharmaceutical compound is at least 2. In some embodiments, the pKa of the pharmaceutical compound is from about 2 to about 7.5. In some embodiments, the pKa of the pharmaceutical compound is from about 1 to about 5. In some embodiments, the pKa of the pharmaceutical compound is from about 7.5 to about 11. In some embodiments, the pharmaceutical composition is formulated as a liquid. In some embodiments, the pKa of the pharmaceutical compound is at least 5. In some embodiments, the pKa of the pharmaceutical compound is from about 5 to about 7. In some embodiments, when formulated as a solution, the pharmaceutical composition has a lower weight osmotic molar concentration than a solution containing a salt comprising the pharmaceutical compound and a complexing agent. In some embodiments, compared to compositions (i) without a chelating agent or (ii) wherein the pharmaceutical compound does not complex with one or more acidic functional groups of the chelating agent, the pharmaceutical composition improves the 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%. In some embodiments, compared to compositions (i) without a chelating agent or (ii) wherein the pharmaceutical compound does not complex with one or more acidic functional groups of the chelating agent, the pharmaceutical composition improves the 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. In some embodiments, the chelating agent comprises a substituted cyclodextrin. In some embodiments, the chelating 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 sulfobutyl ether-β-cyclodextrin (SBEBCD). In some embodiments, the pharmaceutical composition, when formulated as a solution, has a lower weight osmotic molar concentration than a solution containing a salt comprising the pharmaceutical compound and a salt containing a complexing agent. In some embodiments, the drug is formulated for subcutaneous, intramuscular, sublingual, oral, rectal, or intradermal administration.The drug is administered vaginally or intranasally. In some embodiments, when formulated as a solution, the weight osmotic molar concentration of the pharmaceutical composition does not exceed about 850 mOsm / kg. In some embodiments, the pH of the pharmaceutical composition is about 4 to about 7. In some embodiments, the chelating agent is present in an amount of about 10 mg / mL to about 600 mg / mL. In some embodiments, the chelating agent acts as a counterion between 1 to 10 pharmaceutical compound molecules. In some embodiments, the chelating agent further comprises a nonpolar 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 with the nonpolar pore. In some embodiments, the ratio of the chelating agent to the pharmaceutical compound is about 1:1.1. In some embodiments, the ratio of the chelating agent to the pharmaceutical compound is about 1:2. In some embodiments, the ratio of the chelating agent to the pharmaceutical compound is about 1:3. In some embodiments, the ratio of the chelating agent to the pharmaceutical compound is about 1:4. In some embodiments, the ratio of the chelating agent to the pharmaceutical compound is about 1:5. In some embodiments, the ratio of the complexing agent to the drug compound is about 1:6.5. In some embodiments, the solubility of the drug compound as a salt in an aqueous medium is less than about 50 mg / ml. In some embodiments, the solubility of the drug compound as a salt in an aqueous medium is less than about 10 mg / ml. In some embodiments, the solubility of the drug compound as a salt in an aqueous medium is less than about 5 mg / ml. In some embodiments, the solubility of the drug compound as a salt in an aqueous medium is less than about 0.5 mg / ml. In some embodiments, the solubility of the drug compound as a salt in an aqueous medium is less than about 0.1 mg / ml. In some embodiments, the drug compound is ionized. In some embodiments, the pharmaceutical compound includes rotigotine, eletriptan, DXM, midazolam, remdesivir, copanlixetine, levodopa, tigecycline, naloxone, amikacin, 1-amantadine, 2-amantadine, rimantadine, amipridine, rapamycin, clonidine, morphine, hydrocodone, sumatriptan, ropivacaine, bupivacaine, diphenhydramine, granisetron, dechlorin, 2-fluoro-dechlorin, or caspofungin. In some embodiments, the pharmaceutical compound includes a GABAergic agent. In some embodiments, the GABAergic agent includes baclofen, gabosadol, or muscimol, or combinations thereof. In some embodiments, the pharmaceutical compound includes an α-2 agonist. In some embodiments, the α-2 agonist includes clonidine, guanfacine, or tizanidine, or combinations thereof. In some embodiments, the pharmaceutical compound is an ophthalmic agent. In some implementations, ophthalmic agents include aceclidine, atropine, azelastine, brimonidine, cyclopentolate, ketotifen, levobenolol, olopatadine, and others.Pilocarpine, promecaine, tetracaine, timolol, or tropicamide. In some embodiments, the pharmaceutical compound is a bisphosphonate. In some embodiments, the bisphosphonate is alendronate, ibandronate, pamidronate, risedronate, or zoledronic acid, or a combination thereof, or two or more thereof. In some embodiments, the pharmaceutical compound is an antibiotic. In some implementation schemes, the antibiotics include amikacin, amoxicillin, ampicillin, azithromycin, aztreonam, cefaclor, cefadroxil, cefalexin, cefazolin, cefdinir, ceftoran, cefepime, cefdil, cefixime, cefmetazole, cefoperazone, cefotaxime, cefotetan, cefotaxime, cefoxitin, cefpodoxime, cefprozil, cefuroxime, ceftazidime, cefotaxime, cefuroxime, ceftriaxone, cefuroxime, cefalexin, cefepime, cefepime, cefradine, ciprofloxacin, clarithromycin, cloquinolones, colistin, dapavancin, dapoxetine, dapoxetine, and dapoxetine. The drug may contain styramine, doxycycline, ertapenem, eracycline, erythromycin, fosfomycin, gentamicin, imipenem, kanamycin, lefamolin, levofloxacin, linezolid, lincomycin, meropenem, metronidazole, minocycline, moxifloxacin, nalidixic acid, neomycin, nitrofurantoin, orivoxil, penicillin, piperacillin, polymyxin B, quinupristin, retaparin, rifampin, streptomycin, sulfacetamide, sulfadiazine, sulfadiazine, sulfamethoxazole, sulfasalazine, sulfasalazine, teicoplanin, tervacancin, tetracycline, tigecycline, tobramycin, trimethoprim, or vancomycin, or combinations thereof. In some embodiments, the drug compound is an anticoagulant or thrombolytic agent. In some embodiments, the anticoagulant or thrombolytic agent includes alteplase, argatroban, bivalirudin, fondaparinux sodium, lepirudin, streptokinase, or urokinase, or combinations thereof, or two or more thereof. In some embodiments, the pharmaceutical compound is an antifungal agent. In some embodiments, the antifungal agent includes azole antifungal agents. In some embodiments, the antifungal agent includes albendazole, clotrimazole, econazole, fluconazole, isaconazole, itraconazole, ketoconazole, miconazole, posaconazole, tebuconazole, thiabendazole, or voriconazole, or combinations thereof, or two or more thereof. In some embodiments, the antifungal agent is amphotericin B, anidulafungin, caspofungin, flucytosine, micafungin, natamycin, or voriconazole, or combinations thereof, or two or more thereof. In some implementations, the pharmaceutical compound is an antitumor drug. In some implementations, the antitumor drug is afatinib.Alectinib, aristetinib, axitinib, bosutinib, cabozantinib, canertinib, carfilzomib, sildenafil, ceritinib, cimicoxib, cobitinib, dabrafenib, darazatinib, decarsetinib, dovitinib, erlotinib, etorcoxib, felanib, grelasatinib, ibrutinib, ederaglix, imatinib, espinib, ixazomib, lapatinib, lenvatinib The drug may contain, but is not limited to, linxitinib, lonafarnib, masatitinib, motishanib, nilotinib, nintedanib, odanacatib, olaparib, onasipride, osimertinib, palbociclib, pazopanib, peritinib, ponatinib, regorafenib, renalapade, ruxolitinib, celicilib, sorafenib, sunitinib, tandutinib, tepififib, tofacitinib, vandetanib, varitinib, varitinib, valitanib, veripabib, vemectinib, or combinations thereof, or two or more thereof. In some embodiments, the drug compound is an antiviral agent. In some implementation schemes, antiviral agents include abacavir, acyclovir, adefovir, amantadine, ampravir, atazanavir, bictegravir, cidofovir, darunavir, dasabuvir, delavirdine, norinosine, dolutegravir, efavirenz, elvitegravir, emtricitabine, enfuvirtide, entecavir, famciclovir, foscarnet, ganciclovir, grazoprevir, imiquimod, and others. Indinavir, lamivudine, laninamivir, ledipasvir, lopinavir, maraviro, nalfinavir, nevirapine, olbitasvir, oseltamivir, parizol, penciclovir, peramivir, prasafone, podophyllotoxin, raltegravir, ribavirin, rilpivirine, ritonavir, saquinavir, sofosbuvir, stavudine, tenofovir, tipranavirvir, trifluridine, valacyclovir, valganciclovir.Zanamivir or zidovudine, or combinations thereof. In some embodiments, the pharmaceutical compound includes a cardiovascular drug. In some embodiments, the cardiovascular drug includes bretylium, dobutamine, dopexamine, epoprostenol, esmolol, iloprost, nesiritide, nitroglycerin, norepinephrine or phenylephrine, or combinations thereof, or two or more of them. In some embodiments, the pharmaceutical compound includes a central nervous system depressant. In some embodiments, the central nervous system depressant includes alprazolam, nitrazepam, clonazepam, diazepam, dexmedetomidine, dextromethorphan, flurazepam, gabapentin, ketamine, lorazepam, midazolam, oxazepam, propofol, temazepam, or triazolam, or combinations thereof, or two or more thereof. In some embodiments, the drug compound includes a central nervous system stimulant. In some embodiments, the central nervous system stimulant includes amphetamine, cocaine, dextromethorphan, dextroamphetamine, ephedrine, lysine amphetamine, methylamphetamine, methylphenidate, modafinil, phenylephrine, pseudoephedrine, or sibutramine, or combinations thereof, or two or more thereof. In some embodiments, the drug compound includes a local anesthetic. In some embodiments, the local anesthetic includes articaine, benzocaine, bupivacaine, chloroprocaine, cocaine, dibucaine, eticaine, levobupivacaine, lidocaine, malbifocaine, prilocaine, procaine, imicaine, ropivacaine, or tetracaine, or combinations thereof. In some embodiments, the pharmaceutical compound includes an antiemetic. In some embodiments, the antiemetic includes dolasetron, granisetron, ondansetron, or palonosetron, or combinations thereof. In some embodiments, the pharmaceutical compound is an anti-migraine drug. In some embodiments, the anti-migraine drug includes amotriptan, avitriptan, donitriptan, eletriptan, fultriptan, lasmiditan, nalatriptan, rizatriptan, sumatriptan, or zolmitriptan, or combinations thereof. In some embodiments, the pharmaceutical compound includes an anti-Parkinson's disease drug. In some implementation schemes, anti-Parkinson's disease drugs include amantadine, apomorphine, benztropine, benzethrazide, bromocriptine, cabergoline, carbidopa, entacapone, and foscarbidopa.The pharmaceutical compound comprises foslevodopa, levodopa, melevapexole, rasagiline, ropinirole, rotigotine, safenamide, selegiline, tolcapone, or trihexyphenidyl, or combinations thereof. In some embodiments, the pharmaceutical compound includes an antihistamine. In some embodiments, the antihistamine includes avastin, brompheniramine, cetirizine, chlorpheniramine, clomastine, cyproheptadine, desloratadine, dextrochlorpheniramine, diphenhydramine, doxylamine, fexofenadine, hydroxyzine, levocetirizine, loratadine, meclomethasone, promirtine, or tropineamine, or combinations thereof. In some embodiments, the pharmaceutical compound includes an H2 histamine receptor blocker. In some embodiments, the H2 histamine receptor blocker is cimetidine, famotidine, nizatidine, or ranitidine, or combinations thereof. In some embodiments, the pharmaceutical compound includes an opioid substance. In some embodiments, the opioid substance includes buprenorphine, butorphanol, codeine, fentanyl, heroin, hydrocodone, hydromorphone, levonorphine, meperidine, methadone, morphine, naloxone, naltrexone, nalmefenoxate, oxycodone, oxymorphone, pentazocine, sufentanil, tapentadone, or tramadol, or combinations thereof, or two or more thereof. In some embodiments, the pharmaceutical compound is a tyrosine kinase inhibitor. In some embodiments, the tyrosine kinase inhibitor includes bosutinib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, ponatinib, sorafenib, or sunitinib, or two or more thereof. In some embodiments, the pharmaceutical compounds include amipyridine, amifostine, aminocaproic acid, argatroban, asenapine, atropine, bivalirudin, cisatracurium, deferoxamine, desmopressin, gabapentin, lurasidone, milrinone, nicotine, octreotide, pregabalin, rocuronium bromide, terbutaline, tirofiban, tranexamic acid, vecuronium bromide, naprafenamide, or any combination thereof.

[0004] In some respects, this article provides pharmaceutically acceptable salts of compound drugs, including: drug compounds or their enantiomers, mixtures of enantiomers or isotopic variants; or pharmaceutically acceptable salts, solvates or hydrates thereof, wherein the drug compound contains a protonated nitrogen atom and has a pKa of about 1 to about 7; and conjugate bases of complexing agents comprising a plurality of acidic functional groups, wherein at least one of the plurality of acidic functional groups acts as a counter ion of the drug compound, wherein the molar ratio of the conjugate base of the complexing agent to the drug compound is about 1:1 to about 1:10. In some respects, this article provides pharmaceutically acceptable salts of compound drugs, including: drug compounds or their enantiomers, mixtures of enantiomers or isotopic variants; or pharmaceutically acceptable salts, solvates or hydrates thereof, wherein the drug compound contains a protonated nitrogen atom and has a pKa of at least 1; and conjugate bases of complexing agents comprising a plurality of acidic functional groups, wherein at least one of the plurality of acidic functional groups acts as a counter ion of the drug compound, wherein the molar ratio of the conjugate base of the complexing agent to the drug compound is from about 1:1 to about 1:10. In some respects, this article provides pharmaceutically acceptable salts of compound drugs, including: drug compounds or their enantiomers, mixtures of enantiomers or isotopic variants thereof; or pharmaceutically acceptable salts, solvates or hydrates thereof, wherein the drug compound contains a protonated nitrogen atom and has a pKa of about 1 to about 13; and conjugate bases of complexing agents comprising a plurality of acidic functional groups, wherein at least one of the plurality of acidic functional groups acts as a counter ion of the drug compound, wherein the molar ratio of the conjugate base of the complexing agent to the drug compound is about 1:1 to about 1:10. In some aspects, this document provides pharmaceutically acceptable salts of pharmaceutical compounds, including: pharmaceutical compounds or their enantiomers, mixtures of enantiomers, or isotopic variants; or pharmaceutically acceptable salts, solvates, or hydrates thereof, wherein the pharmaceutical compound contains a protonated nitrogen atom and has a pKa of about 4 to about 13; and conjugate bases of complexing agents comprising a plurality of acidic functional groups, wherein at least one of the plurality of acidic functional groups acts as a counter ion of the pharmaceutical compound, wherein the molar ratio of the conjugate base of the complexing agent to the pharmaceutical compound is 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 sulfobutyl ether-β-cyclodextrin (SBEBCD). In some embodiments, the pKa of the pharmaceutical compound is at least 1. In some embodiments, the pKa of the pharmaceutical compound is about 1 to about 7.5. In some embodiments, the pKa of the drug compound is from about 1 to about 5. In some embodiments, the pKa of the drug compound is from about 7.5 to about 13.In some embodiments, the pharmaceutical compounds include 5'-deoxyribonucleoside, 6,7-benzomorphine, amaryl-snake root alkaloids, alkaline earth metal organometallic compounds, Amaryllidaceae alkaloids, anthracene, anthracene rings, apophene, azaspirodecane, azacycloheptane, azobenzene, azole, azoleidine, azoleline, benzo[a]azazide, benzene and substituted benzene, benzimidazole ribonucleoside and ribonucleotide, benzimidazole, benzocycloheptapridine, benzodiazepine, benzo[dioxane], benzo[dioxane], benzo[dioxane], benzo[dioxane], benzo[furan], benzo[pyran], benzo[pyrazole], benzo[thiadiazole], benzo[thiazide], benzo[thiazolium], benzo[thiazolium], benzo[thiazolium], benzo[thiaphene] Benzothiran, benzotriazole, benzoxadiazole, benzoxazine, benzoxazine, benzoxoxazine, biotin, camptothecin, carboxylic acid, Cephalotaxus alkaloids, cinchona alkaloids, cinnamic acid, coumaranthium, cycloheptaphene, condensed phenolic acids and condensed phenolic acid cyclic ethers, diarylheptane compounds, diazanaphthalene, diazacyclohexane, diazine, dibenzocycloheptenene, dioxane, epoxides, ergoline, fatty acyl groups, flavonoid nucleotides, flavonoids, fluorene, furan, furanopyran, glycerophospholipids, other homogeneous nonmetallic compounds, hydroxy acids, ibogan-type alkaloids, imidazodiaza, imidazoribonucleosides and ribonucleotides, imidazodiaza, imidazoribonucleosides, imidazodiaza ... Azopyridine, imidazopyrimidine, imidazothiazole, indene, indene and isindene, indole, indolizidine, isocoumarin, isoindole, isoquinoline, lactam, linear 1,3-diarylpropane, lupin alkaloids, macrolactam, macrolide lactam, macrolide morphine, tetraphenyl, naphthalene, naphthofuran, naphthopyran, nucleoside and nucleotide analogs, organic carbonic acid, organophosphoric acid, organophosphonic acid, organic nitrogen compounds, organic oxygen compounds, organothiophosphoric acid compounds, oxazine, peptide mimics, phenanthrene, phenanthroline, phenol esters, phenol ethers, phenol, phenylpropionic acid, phthaloylisoquinoline, piperazinezazazonium, piperidine, polypeptides Isoprene lipids, pteridine, purine nucleosides, purine nucleotides, pyrazolopyridine, pyrazolopyrimidine, pyridine, pyridopyrimidine, pyrimidine nucleosides, pyrrole, pyrrolidine, pyrrolopyrazine, pyrrolopyridine, pyrrolopyrimidine, quinoline, steroids and steroids, piracetam, tetracycline, tetrahydroisoquinoline, naphthiazine, thienodiazepine, thienopyridine, thienothiazine, thiochromene, thioethers, thiols, thiophene, transition metal salts, triazacyclohexane, triazine, triazole ribonucleosides and ribonucleotides, triazole pyrimidine, triphenyl compounds, hyoscyamine alkaloids, vinca alkaloids, yohimbine alkaloids, or derivatives thereof or combinations thereof. In some embodiments, the pKa of the pharmaceutical compound is from about 1 to about 2.In some embodiments, the pharmaceutical compound includes 1,4-benzodiazepine, amine, amino acid, peptide, androstened steroid, benzenesulfonamide, benzoic acid, benzophenone, benzothiadiazine, biphenyl, carboxylic acid derivative, phenolic peptide, diphenylmethane, ether, halobenzene, isoindoline, nitrogen mustard compound, nitroquinoline, purine 2'-deoxyribonucleoside, purine, pyrazole, pyrimidine or derivatives thereof, retinoids, substituted pyrroles or combinations thereof. In some implementations, the pharmaceutical compounds include apatideson, asunaprevir, azilsartan medoxomil, benzylthiazide, bromfenac, candesartan medoxomil, epinephrine, chlorambucil, chlorothiazide, cladribine, clofarabine, clonazepam, CVT-6883, CX516, dacarbazine, diazoxide, ammodendron, femasartan, flubendazole, flucytosine, fludiazepam, flunitrazepam, ganciclovir, gliclazide, glimepiride, grapravir, guanosine, isobutyllast, isobutylproxen, iodosiloxane. Iopamidol, iopamidol, essatoribine, ixazomib, MB-07803, nateglinide, nepafenamide, OPC-51803, preclinamide, pomalidomide, punicaxin, prilocrine, rengadrosol, rimonaban, selexicam, smetapivir, sulfadimethoxypyrimidine, sulfamethoxypyrimidine, sulfamethoxazole, sulfamethoxazole, sulfadiazine, sulfamethoxazole, sulfadiazine, sulfamethoxazole, tiranaban, tazarotene, thioproline, tolasulfonylurea, tramidil, uracil nitrogen mustard, or combinations thereof. In some embodiments, the pKa of the drug compound is about 2 to about 3. In some embodiments, the pharmaceutical compounds include azobenzene, azole, benzodiazepine, benzene, benzodiazepine, benzothiazine, benzothiazolium, carboxylic acid, phenolic acid, diazonium, diazine, imidazopyrimidine, indole, isoindole, lactam, macrolide naphthalene, nucleoside and nucleotide analogs, organic oxygen compounds, piperidine, isopentenyl alcohol lipids, pteridine, purine nucleoside, purine nucleotide, pyrazolopyrimidine, pyridine, pyrimidine nucleoside, pyrrolopyridine, quinoline, steroid, thienodiazepine, triazine, triazolopyrimidine, or combinations thereof. In some embodiments, the pharmaceutical compound includes 1,4-benzodiazepine, amino acid, peptide, aminotriazine, androstened steroid, sulfaniline, aniline, benzodiazepine, benzenesulfonamide, benzenesulfonyl compound, benzodiazepine, benzoic acid, β-lactam, biphenyl, carbazole, diphenyl ether, diphenylmethane, epothilone estradiol, ether, halobenzene, isoindoline, milbemycin, monoterpenoid, nitroquinoline, oxosteroid, phenoxyacetic acid derivative, phenylbutylamine, phenylcarbamate, benzylamine, phenylpropane, phenylquinoline, pterin, purine 2',3'-dideoxyribonucleoside, purine ribonucleotide, purine and purine derivative, pyrazole, pyrazolo[3,4-d]pyrimidine, pyridinecarboxylic acid, pyrimidine and pyrimidine derivative, sulfaniline, or combinations thereof.In some implementation schemes, the pharmaceutical compounds include acyclovir, adecidyllon, aristotelin, allopurinol, ambrisentan, amerulbant, aminobenzoic acid, aminopterin, aminosalicylic acid, ampravir, anastrozole, para-aminobenzoic acid, asoprilinide, benzocaine, BMS-488043, becanavalin, bromazepam, bumetanide, butanben, cangreloxel, cefixime, cefpirome, chromium picolinate, cidofovir, cilupvir, cinastastat, clarsentan, and chlorhexidine. Diazepam, chloroxazolam, dabrafenib, dapsone, darunavir, diloxapam, diazepam, doxorubicin, dutasteride, edotecan, edofodipine, ecirapine, entecavir, ipilazole, epothilone D, finasteride, fluconazole, flumettafen (18F), folic acid, mepiazole, fosanavir, ganstigmine, GW-501516, halazepam, indocyanine green, inosine, iodamide, iopromide, essaconazole, ixaspirin, KOS-1584, KP-14 61. Lenalidomide, Letrozole, Leucovorin, Levofolinic Acid, Macitentan, Meladiazine, Mercaptopurine, Methotrexate, Methylene Blue, Methionine, Motexafen Gadolinium, Motexafen Lactobionate, Moxiquitin, Nasicarpine, Nitrazepam, Nitrohydroxyquinoline, Olaparib, Obipatamivir, OT-551, Padimafenoxate O, Paliprevir, Patupilone, Penciclovir, Phenylaminosalicylate, PPL-100, Prandtolexa, Quazepam, Rivaconazole, Regorafenib, Regrelor, Ritonavir Roflulast, Roxadustat, Silver Sulfadiazine, Sorafenib, Stanozolol, Sulfabenzoyl, Sulfaacetyl, Sulfaxine, Sulfamethoxine, Sulfamethoxazole, Sulfadoxime, Sulfamethazine, Sulfamethazine, Sulfamethazine, Sulfabenpyrazole, Sulfapyridine, Sulfasalazine, Sulfathiazole, Sulfaisoxazole, Tanetan, Tasosartan, Technetium[99mTc]Desofenine, Technetium[99mTc]Mebrofennin, Tezosentan, Ticagrelor, Terazamine, Traxatabine, Trypan blue, Voriconazole, or combinations thereof. In some embodiments, the pKa of the drug compound is from about 3 to about 4. In some embodiments, the pharmaceutical compound includes 1,4-benzodiazepine, amino acids, peptides, acetanilide, aniline and substituted aniline, anisole, aryl thioether, benzodiazepine, benzofuranone, benzoic acid and its derivatives, benzophenone, β-lactam, biphenyl and its derivatives, bipyridine and oligopyridine, carbodiimide, diphenyl ether, diphenylmethane, epothilone estradiol, ether, haloquinoline, hexacarboxylic acid and its derivatives, imidazole, isoindole, milbemycin, morpholine, phenoxyacetic acid derivatives, benzylamine, phenylpyridine, piperazine, pterin and its derivatives, purine 2',3'-dideoxyribonucleoside, purine and its derivatives, purine and its derivatives, pyrazine, pyrazole, pyridine carboxaldehyde, pyridine carboxylic acid and its derivatives, pyridine sulfonamide, pyridyltriazole, steroid ester, sulfonyl acetanilide, sulfinylbenzimidazole or combinations thereof.In some embodiments, the pharmaceutical compounds include adenosine, amiloride, aminobenzoic acid, aminopyrine, anagrelide, aprepitant, para-aminobenzoic acid, azathioprine, aztreonam, benzocaine, benzonatate, diacetylbenzoic acid, bromazepam, bromotezolam, bumetanide, butanone, calcium cyanamide, cefepime, cefixime, cefotaxime, cefotaxime, cefpodoxime, cefazolin, ceftriaxone, and chlorhexidine. Oxacin, Chromium pyridinecarboxylate, Cloiodohydroxyquine, Dabigatran etexilate, Dabrafenib, Dexlansoprazole, Dexrazoxen, Diazepam, Doxorubicin, Diiodohydroxyquinoline, Entecavir, Etofibrate, Itravirine, Ezogabin, Flumazenil, Flumetazidine (18F), Indigo, Inosine, Nicotinic Acid Inositol Ester, Iophobic Acid, Irbesartan, Iscarbohydrazine, Isoniazid, Itraconazole, Ixaspirone, Lansoprazole Levofloxacin, Levofloxacin, Levomica, Rosiglitazone, Losartan, Lumacartocin, Maindole, Mebendazole, Mercaptopurine, Mercaptopurine, Methotrexate, Metronidazole, Montelukast, Montelukast, Moxifloxacin, Nerapine, Nicotinic acid, Nicorandil, Nicotinamide, Norgestrel, Norgestrel, Olfendazole, Padimazone, Pantoprazole, Penciclovir, Perampanel, Picosulfate Piroxicam, posaconazole, pralatrexate, pralatrexam, procaine ethoxymercurin, pyridoxal, pyridoxal phosphate, riociguat, ritonavir, stanozolol, tanifluoxetine, tasosartan, tenofovir disoproxil fumarate, thiabendazole, tonzodamine, ticagrelor, tinidazole, thioguanine, topiroxetine, torasemide, triamterene, triamterene, vemurafenib, vemodilide, or combinations thereof. In some embodiments, the pKa of the drug compound is about 4 to about 5. In some embodiments, the pharmaceutical compound includes 1,4-benzodiazepine, 1-ribosyl-imidazolium carbamate, 2-benzimidazolyl carbamate, 8-hydroxyquinoline, amine, amino acid, peptide, androstened steroid, acetanilide, aniline and substituted aniline, anthraquinone, aryl sulfide, benzodiazepine, benzoic acid and its derivatives, β-lactam, biphenyl and its derivatives, bipyridine, oligopyridine, bisphosphonates, carbonyl compounds, diphenylmethane, ether, hexachlorocyclohexane, etc. Carboxylic acids and their derivatives, imidazoles, imidazoquinolines, indolequinones, naphthidines, oxosteroids, phenethylamine, phenylbenzimidazoles, phenylhydrazines, phenylpiperidines, phenylpyridines, phenylquinolines, pterines and their derivatives, purine ribonucleotides, purines and purine derivatives, pyrazolo[1,5-a]pyrimidines, pyridine carboxylic acids and their derivatives, pyridine sulfonamides, pyridoindole, quinoline carboxylic acids, styrene, sulfinylbenzimidazoles, trifluoromethylbenzene or combinations thereof.In some implementations, the pharmaceutical compounds include azathioprine, abiraterone, acalcidin, adenosine 5'-phosphoryl sulfate, adenosine monophosphate, AICA ribonucleotide, albendazole, amphetalil, aminoglutethimide, aminohippuric acid, amrinone, atazanavir, aztreonam, banoxanequinone, pineide, diacetylphenidate, carfilzomib, cefotaxime, cefepime, cefotaxime, cefotaxime, cefpodoxime, and ceftazidime. Cefbuprofen, Cefazolin, Ceftriaxone, Coenzyme A, Dexlansoprazole, Ensolazole, Erlotinib, Emeprazole, Estazolam, Etizolam, Etomidate, Itocoxib, Itravirine, Fibrapong, Flavin adenine dinucleotide, Flubetaban (18F), Flubetapyr (18F), Geldermycin, Gentian Violet, Hexanediol, Adelalipide, Impetatape, Indium In-111-oxyquinoline, Nicotinic Acid Inositol esters, Iopoisetic acid, Irbesartan, Lansoprazole, Levosimendan, Loratadine, Lornoxicam, Losartan, LX-2931, Metoxin, Metheprone, Mifepristone, Milrinone, Minoxidil, Nasalidic acid, Nicotinic acid, Osipron, Omeprazole, OSI-930, Obendazole, Oxyquinoline, Perampanel, Pilidisone, Picosulfate, Pitavastatin, Porphyromycin, PX-12, Pyridoxal, Phosphate Pyridoxal, rabeprazole, repaglinide, requimod, retamycin, lidogre, riluzole, risedronate, linaglitone, rosofloxacin, S-8510, sapropterin, ticardisone, tenofovir disoproxil fumarate, tenoxicam, thiabendazole, torasemide, triazolam, tucistat, uristat, varitinib, valproinib, verteporfen, velurubin, vidarabine, velpatinam, vorapazol, or combinations thereof. In some embodiments, the pKa of the drug compound is about 5 to about 6. In some embodiments, the pharmaceutical compound includes 1,4-benzodiazepine, 1-ribosyl-imidazolium carbamate, 2-benzimidazolyl carbamate, 8-hydroxyquinoline, amine, amino acid, peptide, androstened steroid, acetanilide, aniline and substituted aniline, anthraquinone, aryl thioether, benzodiazepine, benzoic acid, β-lactam, biphenyl, bipyridine and oligopyridine, bisphosphonate, diphenylmethane, ether, hexacarboxylic acid, imidazole, imidazoquinoline, indolequinone, naphthidine, oxosteroid, phenethylamine, phenylbenzimidazole, phenylhydrazine, phenylpiperidine, phenylpyridine, phenylquinoline, pterin, purine ribonucleotide, purine and purine derivatives, pyrazolo[1,5-a]pyrimidine, pyridine carboxyl, pyridine sulfonamide, pyridoindole, quinoline carboxylic acid, styrene, sulfinylbenzimidazole, trifluoromethylbenzene or its derivatives or combinations thereof.In some embodiments, the pharmaceutical compounds include 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, 5-methyltetrahydrofolate, abacavir, adefovir dipivoxil, adenine, alprazolam, ALT-2074, amadoxovir, apimod, adenosine triphosphate, avanafil, axitinib, azledipine, benazepril, benzimidazole, bisacodyl, pyricitabine dicitrate, and Brilliant Green. Cabozantinib, Capvirine, Carbidopa, Cefepime, Cirivastatin, Cilabadine, Cisplatin, Clonidipine, Clonisin, Clopidogrel, Cocarboxylase, Dapivirine, Desalazine, Dolastron, Elbasvir, Enalapril, Ethionamide, Etenofoline, Etozoline, Famciclovir, Felodipine, Fulofenin, Forminoben, Fosaspirantan, GTS-21, Hetacillin, Imidacloprid, Imidacloprid Motrin, Incadronic acid, Indebulin, Isooflavin, Iradipine, Kinetin, Lamotrigine, Leadipasvir, Lincitinib, Melanathan, Mesalazine, Urotropine, Moxipril, Mornifluoxetine, NADH, Nevirapine, Nifedipine, Nifluoxetine, Nimodipine, Nisodipine, Nifedipine, Olmesartan, Pazopanib, Pedesine, Perindopril, Phenylezidazine, Pyrapirocin, Pinafenadine, Pioglitazone, Piperacillin, Piperacillin Pradefovir mesylate, prasugrel, prilinsta, procarbazine, pyridoxine, quinapril, ramipril, rilpivirine, ropepofen, ruxolitinib, celecoxib, sildenafil, sonodazole, spiropril, sipofen, tapimod, tarivirine, temopril, temopofen, tenofovir alafenamide, thiamine, triamcinolone acetonide, tropicamide, velpatasvir, cimetidine, zinc pyridinecarboxylate, zolpidem, or combinations thereof. In some embodiments, the pKa of the drug compound is about 6 to about 7. In some embodiments, the pharmaceutical compound includes 1,4-benzodiazepine, 1-ribosyl-imidazolium carbamate, 2-benzimidazolyl carbamate, 8-hydroxyquinoline, amine, amino acid, peptide, androstened steroid, acetanilide, aniline and substituted aniline, anthraquinone, aryl thioether, benzodiazepine, benzoic acid, β-lactam, biphenyl, bipyridine and oligopyridine, bisphosphonate, carbonyl compound, diphenylmethane, ether, hexacarboxylic acid, imidazole, imidazoquinoline, indolequinone, naphthidine, oxosteroid, phenethylamine, phenylbenzimidazole, phenylhydrazine, phenylpiperidine, phenylpyridine, phenylquinoline, pterin, purine ribonucleotide, purine and purine derivatives, pyrazolo[1,5-a]pyrimidine, pyridine carboxyl, pyridine sulfonamide, pyridoindole, quinoline carboxylic acid, styrene, sulfinylbenzimidazole, trifluoromethylbenzene or derivatives thereof or combinations thereof.In some embodiments, the pharmaceutical compounds include 2-amino-1-methyl-6-phenylimidozolo(4,5-b)pyridine, 5-methyltetrahydrofolate, abacavir, adefovir dipivoxil, adenine, alprazolam, ALT-2074, amdoxovir, apimod, avanafil, azledipine, benazepril, benzimidazole, bisacodyl, pyricin Bicocortide, Brilliant Green, capvirline, carbidopa, cerivastatin, cilazapril, cisplatin, clovidipine, clonidine, clopidogrel, cocarboxylase, dapoxetine, delamani, desarazine, dolasetron, elbasvir, enalapril, etofosin, etorazoline, and famciclovir. Viagra, Felodipine, Flofenoxan, Forminoben, Fosapitan, GTS-21, Hetacillin, Imidacloprid, Imiquimod, Incardonic acid, Indebulin, Issubanlan, Iradipine, Kinetin, Lamotrigine, Leadipasvir, Melanathana, Mesalazine, Urotropine, Moxipril, Mornifluoxetine, Nevirapine, Nifedipine, Nifluoxetine, Nimodipine, Nisodipine, Nifedipine, Olmesartan, Pazopanib, Pedesine, Perindopril, Phenylezid, Pyrapoplatin, Pinafenidil, Pioglitazone, Piperacillin, Pradefovir Mesylate, Prasugrel, Prinstat, Procarbazine, Pyridoxine, Quinapril, Ramipril, Rilpivirine Ropepoxetine, Ruxolitinib, Celicillin, Sildenafil, Sonicate, Ropril, Sipofen, Tapimod, Talivirine, Temopril, Temopoxetine, Tenofovir Acetonide, Thiamine, Qundopril, Topicamid, Velpatasvir, Cimetazidine, Zinc Pyridinecarboxate, Zolpidem, Acarbose, Amaryl, Acaratadine, Alfentanil, Alfuzosin, Amitriazine, Amisulpride, Amoxicillin, Ampicillin, Amlodipine, Triamcinolone, Aripiprazole, Asenapine, Atemexazole, Azapirol, Bambucil, Cefaclor, Cefadroxil, Cefdinir, Cefprozil, Cefalexin, Librium, Clozapine, Dafopril The following are listed: dasatinib, diethylamine benzophenone, domperidone, dazolidin, doxapram, doxazosin, drotavirine, iriconazole, ipramone, flavoxate, flubancerine, flupiridine, midazoline, indinavir, ketamine, ketotifen, lapatinib, loxapine, mabifocaine, methoxytetracycline, mosonidin, nefazodone, olanzapine, ondansetron, benzotriazine, pimecrolimus, promocaine, prazosin, quetiapine, ranolazine, rupatadine, spruitine, terazosin, buphenazine, ticlopidine, tizanidine, tofacitinib, trazodone, trimethoprim, valacyclovir, valganciclovir, ziprasidone, or combinations thereof.

[0005] In some embodiments, the pKa of the pharmaceutical compound is about 7 to about 8. In some embodiments, the pharmaceutical compound includes amaryl-snake root alkaloids, 1,4-benzodiazepines, 2,3,5-trisubstituted thiophenes, alcohols and polyols, amines, amino acids or peptides, acetoanilides, anisoles, benzodiazepines, benzo[a]aryl ... Benzo[a]oxazine, benzo[a]oxazine, benzylamine, benzylisoquinoline, benzylpiperidine, β-lactam, biphenyl, carbazole, carbohydrates, carbonyl compounds, carboxylic acids, cycloheptaphene, diarylheptane compounds, diazanaphthalene, diazacyclohexane, diazine, dibenzocycloheptene, dibenzodiazepine, dibenzothioazepine, dibenzo[a]oxazine, dibenzo[a]oxazine, diphenylmethane, ergoline, flavonoids, flavonoids, halogens Benzene, heteropeptides, hydrogenated pyridine, indene, indole, indoline, isoquinoline, isoquinolinone, lactam, linear diarylheptane compounds, lysergic acid, macrolactam, macrolide lactam, monoterpenoids, morpholine, n-acylpiperidine, n-alkylindole, tetraphenyl, naphthopyranone, naphthopyran, n-phenylurea, organic nitrogen compounds, organic oxygen compounds, oxazine, pentacarboxylic acid, peptide mimics, phenanthrene, phenethylamine Phenolic ethers, benzylamine, phenylpiperidine, phenylhyoscyamine, piperazine, piperidine carboxylic acid, piperidine, polypeptides, isopentenol lipids, pyridazine and its derivatives, pyridine, pyrimidine 2'-deoxyribonucleoside, pyrimidine nucleoside, pyrimidine, quinoline carboxylic acid, quinoline, steroid esters, steroids, tetrabenzoquinone, tetracycline, tetrahydroisoquinoline, thienopyridine, thiophene, hyoscyamine alkaloids, xylene, yohimbine alkaloids or their derivatives or combinations thereof. In some implementations, the pharmaceutical compounds include acarbose, amorol, acatadine, alfentanil, alfuzosin, aripiprazole, ampicillin, amoxicillin, hexamethylmelamine, altropane, axidiclofen, amdecanocillin, aminolevulinic acid, amisulpride, amoxicillin, ampicillin, amrubicin, triamcinolone, aripiprazole, asenapine, atemetazole, AV-412, azapiridone, azatadine, bamectin, barnidipine, benidipine, bifenproxetine, bleomycin, buprofenserin, branicline, buffentanil, bupivacaine, buspirone, caliprazine, and carbomer. Pilotinib, Cathinone, Cefaclor, Cefadroxil, Cefdinir, Cefprozil, Cefadroxil, Cefadroxil, Cefalothin, Quinoline, Cetirizine, Clocycline, Librium, Chlortetracycline, Cilansetron, Clozapine, Dafopritin, Dapiprazole, Dasatinib, Disepine, Diethylamine, Domperidone, Dozolidinedazole, Dovitinib, Doxapram, Doxazosin, Doxycycline, Drotaverine, Edompex, Ifluconazole, Exalucin, Erudoline, Enalapril, Enzatolin, Epradone, Ergonovine, Ergotamine, EVT-101, Ezastolin, Faneclin, Femprespritz, Finafloxacin, FlavovirideFlubanoxetine, flunarizine, flupiridine, hexyl aminolevulinate, hydroxyzine, ellaprilin, ipraridone, midazolam, indinavir, josamycin, ketamine, ketotifen, lapatinib, larazotide, lesoprazole, levobupivacaine, levocetirizine, lidocaine, linaloolide, lofexidine, chloramphenicol, lopiperazole, loxapine, lysergic acid diethylamide, manidipine, methylphenidate Pralidazole, Mabivovacaine, Methoxycycline, Methylaminolevulinate, Methylergonovine, Mesiergosterol, Miglitol, Motisanil, Mosonicin, Naloxone, Naruzotan, Nefazodone, Nettopitan, Olanzapine, Olanzapine, Ondansetron, Oxytetracycline, Palonosetron, Piperepidone, Benzotriazine, Phenoxybenzamine, Pirenzepine, Pilamicin, Pimetcillin, Benzyl Thiazide, promocaine, prazosin, pralofenadine, prx-08066, pyrimethamine, quetiapine, RAF-265, raloxifene, ranolazine, reboxetine, remifentanil, resinamine, reserpine, rifampin, rifapentine, rocuronium bromide, ropivacaine, rupatadine, safenamide, saxagliptin, septiline, SNX-5422, sorimycin, suvogoli, SUVN-502, talac ferritin α, telithromycin, terazosin, buphenazine, ticlopidine, tepififibidine, tizanidine, tofacitinib, trabectedin, trazodone, trimethoprim, trimethoprim, temasolazoline, valacyclovir, valganciclovir, vallociclovir, vatocitabine, verneclax, voglibose, yohimbine, ziprasidone, zolquida, or combinations thereof. In some embodiments, the pKa of the pharmaceutical compound is about 8 to about 9. In some embodiments, the pharmaceutical compound includes 1-benzopyran, 1-benzothiaran, 1-phenyltetrahydroisoquinoline, alcohols, polyols, amines, amino acids, peptides, aminoquinoline and derivatives, androstened steroids, acetanilide, anisole, aryl sulfide, hydroquinone, benzylsulfonamide, benzo-1,4-dioxane, benzodiazepine, benzoic acid and derivatives, benzoquinoline, benzylamine, benzyl ether, benzylpiperidine, β-lactam, biphenyl and derivatives, carbazole, carbohydrates and carbohydrate conjugates, carbonyl compounds, carboxylic acid derivatives, phenolic peptides, dibenzo[a]azine, dibenzo[thio]azine, dibenzo[oxo]azine, diphenylacetonitrile, diphenylfuran, diphenylmethane, ethers, fatty acids and conjugates. Fentanyl, Amaryllidaceae alkaloids of the snowflake type, halobenzenes, hydrogenated pyridine, imidazoline, indazole, indole, indoloquinoline, isoquinolinones and derivatives, isoxazoline, lysergic acid and derivatives, methoxybenzene, monoterpenoids, morpholine, n-alkylindole, naphthidine, oxadiazole, pentacarboxylic acids and derivatives, phenethylamine, phenothiazine, phenothiazine, phenoxy compounds, benzylamine, phenylnaphthalene, phenylpiperidine, phenylpropane, phenylpyridine, phenylpyrrolidine, phenylquinoline, piperazine, piperidine carboxylic acid and derivatives, purines, pyrimidines and pyrimidine derivatives, pyrrolylpyridine, quinoline carboxamide, quinoline carboxylic acid, styrene, substituted pyrroles, sulfonylaniline, tetracarboxylic acids and derivatives, thiazoles, thiophene carboxylic acids and derivatives.Trifluoromethylbenzene, xylene, or their derivatives or combinations thereof. In some embodiments, the pharmaceutical compounds include acepromethazine, acephenanol, arubicin, avalastine, afatinib, afoxifene, aranoxin, amiodarone, aminon-13, ammonium molybdate, aminonaphthylfentanyl, amorolfen, amoxapine, acridine, amicaine, anamoxifene, aniridine, apirin, acetophenone, aclonidine, articaine, azoxifen, azimadolin, aspartame, astemizole, atrasentan, azelastine, azithritol, bedaquiline, benzylfentanyl, bosutinib, bromoxynil, bromhexine, bukrazine, bupivacaine, buprofentanyl, bupivacaine, bupropion, buprofentanyl, caldarazole, captopril, carbiprazine, carfentanil, carvedilol, cefminox, cefotiam, and sigrosiform. Viagra, Ceftriaxone, Chlorprocaine, Clopidogrel, Chlorpyrifos I-131, Cinnarizine, Ciprofloxacin, Cisapride, Clarithromycin, Chlorpheniramine, Clomocycline, Clonidine, Clopistatin, CNS-5161, Cocaine, Cyclopemycin, Cyclopentolate, Cycloserine, Cyproheptadine, Davallin, Daunorubicin, DDP-225, Demeclocycline, Delencyclohexane, Desvenlafaxine, Dicyclovir, Dihydroergotamine, Diltiazem, Dimethicone, Diphenhydramine, Diphenhydramine, Diphenoxylate, Diphenhydramine, Dofetilide, Donepezil, Dotarizine, Doxorubicin, Doxylamine, Drolidine, D-Serine, Dacronin, Edesmazine, Edivoxetine, Iraqda, Eletriptan Iligrax, Imestin, Enoxacin, Eperisone, Epinastin, Epinephrine, Epirubicin, Erythromycin, Exopeniacin, Famotidine, Fasudil, Fentanyl, Flupentixol, Fluphenazine, Flurazepam, Frodex, Fluriloxetine B, Gaboroxadol, Gadofosamide, Galantamine, Garalfloxacin, Gatifloxacin, Grosexatinib, Glucosamine, Glypromate, Granisetron, Gapaverine, Haloperidol, Hydrocodone, Hydromorphone, Idarubicin, Imatinib, Imolamin, Indium Pentate In-111, Irosanadine, Isminir, Isoproterenol, Isispentide, Isocortin, Ilmetazidine, Ilmetazidine, Ilmetazidine, Ilmetazidine, Ilmetazidine, Ilmetazidine, Ilmetazidine, Ilmetazidine, Ilmetazidine, Ilmetazidine, Ilmetazidine, Ilmetazidine, Ilmetazidine, Ilmetazidine, Ilmetazidine, Ilmetazidine, Ilmetazidine, L-Asparagine, Levobupivacaine Cobadone, Lincomycin, Lobeline, Lofentanil, Lomefloxacin, L-Threonine, Thiantrone, Lumaperone, Lurasidone, LY-517717, Demamagazine, Macitinib, Meclozine, Mepiridazine, Mepiridazine, Mesodazine, Mesodazine, Methadazine, Midodone, Miglucostat, Miglucostat, Mimosolic acid, Minocycline, Moxicillin, Naloxicillin, Nebivolol, Nafenavir, Nicardipine, Nicergoline, Nicotine, Norepinephrine, Norfloxacin, Normethadone, Oxcapecidone, Oxymethylfentanil, Ophenazine, Osimertinib, Obubucaine, Oxybutynin, Oxycodone, Hydroxybenzylphenamine, Palfurapine, Palbociclib, Palpanridone, Palirodone, Pargiline, PBT-1033, PeritinibTrisodium pentiate calcium, trisodium pentiate zinc, pentostatin, perphenazine, meperidine, p-flufentanyl, indole, fenmetrazine, bensulfuron-methyl, pimozide, pipampazone, pipexazol, piperoxithiazide, pyridinole, ponatinib, PPI-1019, pricaine, procaine, prochlorperazine, proflavin, promecaine, piperazine, propyrazole, propylthiazide, prooxycaine, protoprolol, prunasine Carpipride, PRX-07034, Quinolidone, Quinuprin, Rabemodil, Ranitidine, Rasagiline, Remasiamide, Remopride, Lenzapride, Rifabutin, Rifarazil, Relapade, Risperidone, Rivasidine, Robazotane, Lorapitane, Roxatidine Acetate, Saquinavir, Salfloxacin, Salizotan, Selegiline, Serine, Serindole, Sincalitone, Sitagliptin, Soriberi Naxin, Sparfloxacin, Sodomycin, Sufentanil, Sulpiride, Taclopramide, Talaposta, Tamoxifen, Taliquida, Technetium TC-99M Tetraphosphine, Tegaserod, Terbinafine, Terconazole, Tetracaine, Tetracycline, Thiophanolfentanil, Thiproprazole, Thioridazine, Tevothiazol, Somizole, Thionepril, Tigecycline, Tocainide, Topazol, Toremifen, Trifluoperazine, Trimebutine, Trimebutine Benzylamine, tropineamine, triprolidine, tromethamine, tubocurarine, udenafil, varanoslin, velipanib, venlafaxine, vevicivol, vilazolone, veloxacin, vincristine, vindesine, vinorelbine, styraxamine, vortioxetine, zariloden, zantenol, zanapezil, zotepine, zuchlorothiazol, α-methylfentanyl, α-methylthiofentanyl, β-hydroxythiofentanyl, or combinations thereof. In some embodiments, the pKa of the pharmaceutical compound is about 9 to about 10. In some embodiments, the pharmaceutical compounds include 1-benzopyran, 1-benzothiaran, 1-hydroxy-4-unsubstituted benzene compounds, 4-quinoline methanol, 5'-deoxy-5'-thionucleoside, amines, amino acids, peptides, aminophenyl ethers, aminoquinoline, acetanilide, anisole, anthraquinones, hydroquinone, benzyl sulfonamide, benzo-1,4-dioxane, benzodiazepine, benzoic acid, benzyl nitrile, benzoquinoline, benzoxazinone, benzoyl, benzyl alcohol, benzyl ether, benzylpiperidine, β-lactam, biphenyl, bisphosphonates, carbazole, carbohydrates and carbohydrate conjugates, indigo, phenolic peptides, and dibenzodiazepines. Dibenzothiocyanate, dibenzooxane, dicarboxylic acid, diphenylacetonitrile, diphenylmethane, diterpenoids, ethers, fentanyl, glycerophosphate serine, halobenzene, heteropeptides, hydrogenated pyridine, hydrogenated quinoline, hydroxypyridine, indazole, indole carboxylic acid, indole, indoleline, indole-1, indole-1, quinoline, indole-1, isoquinoline quinone, lysergic acid, methoxybenzene, naphthidine, nitrobenzene, nitroquinoline, organic sulfonic acids, pentacarboxylic acid, phenethylamine, pheniramine, phenothiazine, phenoxazine, phenoxy compounds, phenoxyacetic acid, phenylacetamide, phenylbutylamine, benzylamine, phenylpiperidine, phenylpropane, phenylhyoscyamine, piperazine, piperidine carboxylic acid,Pregnane steroids, purines and purines, pyridinium, quinoline carboxylic acids, quinolones, steroid esters, styrene, substituted pyrroles, sulfonyl aniline, tametraline, thiophene carboxylic acids, toluene, trifluoromethylbenzene, tryptamine, tyrosol, or derivatives thereof, or combinations thereof. In some embodiments, the pharmaceutical compounds include (3S)-3-methyl-D-aspartic acid, isoclin, 13-deoxydoxorubicin, 3-allyl fentanyl, 3-methylfentanyl, 4-phenylfentanyl, 7-hydroxycryocystis, acebutolol, S-adenosylmethionine, adoloxin, alendronate, aliximazine, aliskiren, amotriptan, alogliptin, apralol, ambroxol, amibelonone, amikacin, amigonic acid, aminocontin, amitriptyline, amlodipine, amphotericin B, antazoline, and aspirin. Aprilinine, abaclofen, abecasin, abutamine, afortrol, arelolomo, aprolol, arylacetamide, atenolol, atoxetine, atosiban, atropine, azithromycin, baclofen, babutrol, badoxifen, betcarin, benflurex, benzalkonium chloride, benzalkonium chloride, benzylpenicillin, betasine, benprodil, besifloxacin, betahistine, betahistine, betahistine, betahistine, betahistine, betahistine, betahistine, betahistine, betahistine, betahistine, betahistine, betahistine, betahistine, betahistine, betahistine, betahistine, betahistine, betahistine, betahistine, betahistine, betahistine, betahistine, betahistine, betahistine, betahistine, betahistine, betahistine, betahistine, betahistine New, Bromhexine, Bromdapoxetine, Brompheniramine, Butifrolol, Blavallorol, Butenafine, Cabergoline, Canphosphatamide, Carbocysteine, Carteolol, Caspofungin, Sildenafil, Cefalexin, Cefoloza, Celiprolol, Chlorpheniramine, Chlorpromazine, Chlorprothixone, Cilastatin, Cincocaine, Cialis, Citalopram, Clomastine, Clenbuterol, Chlorcarmine, Clofazimine, Clomiphene, Clomipramine, Cobitinib, Codeine, Colestipol, CP-122721, Cymemazine, Cyclobenzaline, Cyclomethasone, Cystine Indigoferazone, Dapavancin, Dapoxetine, Dapoxetine, Dalinpacin, Desclopramide, Demetiline, Desloratadine, Dextromethorphan, Dextromethorphan Maleate, Dextromethorphan, Dextromethorphan, Dextropropoxyphene, Dextrothyroxine, Dezocine, Diphenoxyphene, Dihydrocodeine, Metformin, Metformin, Diphenidol, Dipiformin, Diprenorphine, Dierythromycin, D-methionine, Dobutamine, Dopamine, Doripenem, Duthipine, Doxepin, Dronedarone, Duloxetine, Encani, Enclomiphene, Ephedrine, Epicept NP-1, Eribulin, Ertapenem, Etapril, Esmolol, Ethambutol, Profenamide, Ethylmorphine, Eticaine, Ethyltryptamine, Fennotecal, Fensipril, Ferrous Glycine, Fexofenadine, Franbaconil, Fingolimod, Flucainide, Fluoxetine, Fluspiline, Fluvoxamine, Formoterol, Freund's Mycelium, Gabapentin, Gadobacterium, Gadolinium Trisodium, Gadolinium Dimeglumine, Gadolinol, Gadoxetine, Gemmifloxacin, Glutamic Acid, Glutathione, Glutathione Disulfide, Glycine, Golomod, Glucagliptin, Granisetron, Halofurone, HeroinHecticetine, Heccaine, Histamine, Histidine, Homatropine, Huperzine A, Huperzine B, Hydroxyamphetamine, Hydroxychloroquine, Hyoscyamine, Ibandronate, Efenidil, Imipramine, Indacaterol, Ioflupane I-123, Irinotecan, Iotaline, Isopin, Ivabradine, K201, Kanamycin, Labetalol, L-Alanine, L-Aspartate, L-Citrile, L-Cysteine, L-Lercanidipine, Leukotriene C4, Levofloxacin, Levoamlodipine, Levobetalol, Levobuprofen, Levodopa, Levomethadone, Levomilnacipran, Levofenoxate, Levothyroxine, L-Glutamine, Linagliptin, Ioxelonine, Compound Thyroxine, L-Isoleucine, LJP 1082, L-Leucine, Lometrexed, Loperamide, L-Phenylanine, L-Threonine, L-Tryptophan, L-Tyrosine, Fenflurinol, L-Valine, Lysylcycline, Sulfamethoxazole, Magnesium Glycine, Mefloxacin, Melphalan, Meropenem, Metarhamnol, Methadone, Acetatemethadone, Methionine, Levopromethazine, Methoxyamine, Methyldopa, Methylphenidate, Methemolol, Methoxane, Metoclopramide, Metoprolol, Methyltyrosine, Mexiletine, Mibeprazole, Milnacipran, Mirabelon, Mitansinol, Mitoxantrone, MN-305, Morphine, Moxifloxacin Nadolol, Naftifine, Nalmefine, Naratriptan, Naronapride, Natamycin, Nemonoxacin, Netilmicin, Nitroarginine, NPS-2143, NS-2359, Nystatin, Oglufanine, Odanoterol, Olopatadine, Homoharringtonine, OPC-28326, Osinaline, Osanetin, Oseltamivir, Oxaniquine, Olofoline, Serotryptophan, Oxenolol, Pamidronate, Paroxetine, Paroxetine, Penbuprolol, Pentoxyverine, Pentoxyverine, Pergolide, Phenylephrine, Indoxamine, Feniramine, Phentoxetine Phenylephrine, phenylephrine, phenylpropanolamine, pholcodine, phosphatidylserine, piperazine, indolarol, piperazine, pirarubicin, pibuterol, pisenoside, polyprezil, plasinostat, prasinosteroid, procainamide, procaterol, propylcycline, promethazine, promirtine, propafenone, propoxyphene naphthalenesulfonate, propranolol, PRX-03140, pseudoephedrine, PX-478, quarfloxin, quinidine, quinidine barbiturate, quinine, repinolatin, retaparin, ribostamycin, ritodrine, rizatriptan, ronacarbose, roxithromycin Sulfomycin, Salbutamol, Salmeterol, Saladulant, Selenomethionine, Seroxetine, Serotonin, Sertraline, Sibutramine, Cilodoxin, Cilamecamide, Sorabelon, Sotalol, Spectinomycin, Spiramycin, Sumatriptan, Sunitinib, Tamsulosin, Tandutinib, Tapentam, TAS-108, Taurine, Tetravancin, Terbutaline, Terfenadine, Telmilifen, Tersofensin, Tetrodotoxin, TG-100801, Tigabin, Ticapride, Tilmicosin, Timolol, Tobramycin, Topotecan, TramadolThe pharmaceutical compound may contain, but is not limited to, tranexamic acid, triethylenetetramine, trifluoropromethazine, trihexyphenidyl, trimetazidine, tramipamine, trovafloxacin, tyramine, ubenmethazine, vancomycin, vandetanil, varenicline, vecuronium bromide, verapamil, vinakalan, vilancoside, vilanterol, vildagliptin, zolmitriptan, α-methylacetylfentanyl, α-methylfentanyl, β-methylfentanyl, or combinations thereof. In some embodiments, the pKa of the pharmaceutical compound is from about 10 to about 13. In some embodiments, the pharmaceutical compounds include 2,6-dimethyl-3-benzo[a]arene, alkaline earth metal oxides, alkyl thiols, amines, amino acids, peptides, aminopyridine, aminoquinoline, hydroquinone, benzoic acid, benzo[a]quinoline, β-lactam, cholic acid, alcohols, biphenyl, bisphosphonates, carbazole, carbohydrates and carbohydrate conjugates, carboxylic acid derivatives, cyclohexylamine, phenolic peptides, dibenzo[a]azine, diphenylmethane, ethers, fatty acids and conjugates, guanidine, halobenzenes, heteropeptides, indole carboxylic acids, indole, indoline, monoterpenoids, n-arylamides, organic sulfonic acids, peptide-peptide hybrids, phenethylamine, fenilam, phenylbutylamine, benzylamine, phenylpiperidine, phenylpropane, phenylpropylamine, phenylpyridine, piperidine carboxylic acid, purines and purine derivatives, pyrazolylpyridine, pyrimidines and pyrimidine derivatives, tetracarboxylic acids, tryptamine, urea, xylene or its derivatives or combinations thereof. In some implementations, the pharmaceutical compounds include 2-iminobiotin, abaricicliz, ABT-510, afanotide, guanidine, acevirine, avimopan, amantadine, AMD-070, amifostine, aminocaproic acid, amodiaquine, amphetamine, anatibant, apomorphine, argatroban, avirapamil, atemod, atetidil, bedoradine, benzodiazepine, betanidine, bisifafine, bivalirudin, brotalisin, buprenorphine, butorphanol, butiline, capreomycin, urea peroxide, cefotoxin, ceritinib, cetrorecliz, chlorhexidine, chloroquine, chlorpheniramine, cinacalcet, trifluoroacetic acid, cortisone, Cr665, creatine, crizotinib, cysteine, and CZEN. 002, Davapiridine, Dafenadine, Isoquinoline, Deferoxamine, Degarelix, Decaseline, Denibulin, Desipramine, Dilorelin, Desmopressin, Dexfenfluramine, Dextromethorphan, Diethylseminated spermine, Dihydrostreptomycin, Diisopropyridine, Eflunomide, Envemycin, Etorphine, Benzovasopressin, Fencanfamin, Fenethinoline, Fenfluramine, Fenodopan, Fexolodine, Furazolidone, Furotriptan, Thiamine, Gadolinate, Gadolinol, γ Gamma-aminobutyric acid, ganirilac, gentamicin, gonadorelin, goserelin, guanazole, guanethidine, guanidine, halopantran, hesonaline, histamine relin, hydroxyproline, hydroxyethylsulfonic acid hydroxyastramonium, ibutilide, atebandonide, imipenem, indapoxetine, indecarboxylic acid, iodobenzylguanidine, iodobenzylguanidine sulfate I-123, isomethime, labbedimir, L-aminocarnitine-succinyl-leucyl-arginine aldehyde diethyl acetal, lanreotide, L-arginine, L-efluoroornithine,Levodocin, Levocabastine, Lysine Amphetamine, Lisinopril, Lixifenatide, L-Lysine, Lorcaserin, L-Proline, Magnesium Oxide, Maprotiline, Maraviro, Mecaramine, Memantine, Mefenamic Acid, Metformin, Metformin, Midomafelamine, Nafarelin, Nabuphine, Naltrexone, Naphazoline, Nelamesin, Neridonic Acid, Nintedanib, Nor-Noha Nortriptyline, Benzylpropionate, Onipetide, Octreotide, Olcegepant, Ornithine, Omisaban, Olmisaban, Oxymethazine, Oxymorphine, Pabistat, Pacitrinet, Pemetrexed, Pentamicil, Pentazocine, Peramivir, Piperacillin, Phenylephrine, Phenformin, Phentermine, Pimagateline, Piracetam, Plesoxanol, Polymyxin B Sulfate, Pozaniclone, Pramipexole, etc. Rebamectin, Prezatide, Primaquine, Flusalamide, Cloguanidine, Propyltrimethylammonium Chloride, Protriptyline, Tiamethoxam, Quinacrine, Remolanine, Rifaximin, Amantadine, Rivanectin, Romidixin, Ropinirole, Rotigotine, Salazine, Saplatin, Serotonin, SGS-742, Sitamoebasil, SNS-032, Somatostatin, Spermine, SQ-109, Squalamine, Streptomycin, T131, Tafen Noquine, talocrexin, tanspiramycin, tecasmizole, tenocandin, terlipressin, temorepinephrine, tecocrylide, tetrahydrozoline, tezampin, tepazolidin, tirofiban, tolazoline, tolterodine, taurine, tranexamic acid, triptorelin, uracilide, urea C-13, vapitaxine, vintafolide, purpuric acid, WX-UK1, xylometazoline, zanamivir, or combinations thereof. In some embodiments, the pharmaceutical composition is a solid. In some embodiments, the pKa of the pharmaceutical compound is at least 2. In some embodiments, the pKa of the pharmaceutical compound is from about 2 to about 7.5. In some embodiments, the pKa of the pharmaceutical compound is from about 1 to about 5. In some embodiments, the pKa of the pharmaceutical compound is from about 7.5 to about 11. In some embodiments, the pharmaceutical composition is formulated as a liquid. In some embodiments, the pKa of the pharmaceutical compound is at least 5. In some embodiments, the pKa of the pharmaceutical compound is from about 5 to about 7. In some embodiments, the pharmaceutical composition, when formulated as a solution, has a lower weight osmotic molar concentration than a solution containing a salt comprising a drug compound and a salt containing a complexing agent. In some embodiments, compared to a composition (i) without a complexing agent or (ii) wherein the drug compound does not complex with one or more acidic functional groups of a complexing agent, the pharmaceutical composition improves the solubility of the drug compound by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or about 100%. In some embodiments, compared to a composition (i) without a complexing agent or (ii) wherein the drug compound does not complex with one or more acidic functional groups of a complexing agent, the pharmaceutical composition improves the solubility of the drug compound by about 2-fold, about 3-fold, or...Approximately 4 times, approximately 5 times, approximately 6 times, approximately 7 times, approximately 8 times, approximately 9 times, approximately 10 times, approximately 20 times, approximately 30 times, approximately 40 times, or approximately 50 times. In some embodiments, the chelating agent comprises a substituted cyclodextrin. In some embodiments, the chelating 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 sulfobutyl ether-β-cyclodextrin (SBEBCD). In some embodiments, the pharmaceutical composition, when formulated as a solution, has a lower weight osmotic molar concentration than a solution containing a salt comprising the pharmaceutical compound and a salt comprising the chelating agent. In some embodiments, the pharmaceutical composition is formulated for subcutaneous, intramuscular, sublingual, oral, rectal, vaginal, or intranasal administration. In some embodiments, when formulated as a solution, the weight osmotic molar concentration of the pharmaceutical composition does not exceed approximately 850 mOsm / kg. In some embodiments, the pH of the pharmaceutical composition is approximately 4 to approximately 7. In some embodiments, the complexing agent is present in an amount from about 10 mg / mL to about 600 mg / mL. In some embodiments, the complexing agent acts as a counterion between 1 to 10 drug compound molecules. In some embodiments, the complexing agent further comprises a nonpolar pore. In some embodiments, the pharmaceutical composition further comprises an additional molar equivalent of the drug compound, wherein the additional molar equivalent of the drug compound is unionized and complexed with the nonpolar pore. In some embodiments, the ratio of the complexing agent to the drug compound is about 1:1.1. In some embodiments, the ratio of the complexing agent to the drug compound is about 1:2. In some embodiments, the ratio of the complexing agent to the drug compound is about 1:3. In some embodiments, the ratio of the complexing agent to the drug compound is about 1:4. In some embodiments, the ratio of the complexing agent to the drug compound is about 1:5. In some embodiments, the ratio of the complexing agent to the drug compound is about 1:6.5. In some embodiments, the drug compound, as a salt, has a solubility in an aqueous medium of less than about 50 mg / mL. In some embodiments, the drug compound as a salt has a solubility in an aqueous medium of less than about 10 mg / ml. In some embodiments, the drug compound as a salt has a solubility in an aqueous medium of less than about 5 mg / ml. In some embodiments, the drug compound as a salt has a solubility in an aqueous medium of less than about 0.5 mg / ml. In some embodiments, the drug compound as a salt has a solubility in an aqueous medium of less than about 0.1 mg / ml. In some embodiments, the drug compound is ionized. In some embodiments, the drug compound includes rotigotine, eletriptan, DXM, midazolam, remdesivir, copanlixine, levodopa, tigecycline, naloxone, amikacin, 1-amantadine, 2-amantadine, rimantadine, amipridine, rapamycin, clonidine, morphine, hydrocodone, sumatriptan, ropivacaine, bupivacaine, diphenhydramine, granisetron, etc.The drug compound includes dechlorin, 2-fluoro-dechlorin, or caspofungin. In some embodiments, the drug compound includes a GABAergic agent. In some embodiments, the GABAergic agent includes baclofen, gaposidoxuron, or muscarinic acid, or combinations thereof. In some embodiments, the drug compound includes an α-2 agonist. In some embodiments, the α-2 agonist includes clonidine, guanifaxine, or tizanidine, or combinations thereof. In some embodiments, the drug compound is an ophthalmic agent. In some embodiments, the ophthalmic agent includes acetylcholine, atropine, azelastine, brimonidine, cyclopentolate, ketotifen, levobunolol, olopatadine, pilucarpine, promecaine, tetracaine, timolol, or tropicamide. In some embodiments, the drug compound is a bisphosphonate. In some embodiments, the bisphosphonate is alendronate, ibandronate, pamidronate, risedronate, zoledronic acid, or combinations thereof, or two or more of these. In some embodiments, the drug compound is an antibiotic. In some implementation schemes, the antibiotics include amikacin, amoxicillin, ampicillin, azithromycin, aztreonam, cefaclor, cefadroxil, cefalexin, cefazolin, cefdinir, ceftoran, cefepime, cefdil, cefixime, cefmetazole, cefoperazone, cefotaxime, cefotetan, cefotaxime, cefoxitin, cefpodoxime, cefprozil, cefuroxime, ceftazidime, cefotaxime, cefuroxime, ceftriaxone, cefuroxime, cefalexin, cefepime, cefepime, cefradine, ciprofloxacin, clarithromycin, cloquinolones, colistin, dapavancin, dapoxetine, dapoxetine, and dapoxetine. The drug may contain styramine, doxycycline, ertapenem, eracycline, erythromycin, fosfomycin, gentamicin, imipenem, kanamycin, lefamolin, levofloxacin, linezolid, lincomycin, meropenem, metronidazole, minocycline, moxifloxacin, nalidixic acid, neomycin, nitrofurantoin, orivoxil, penicillin, piperacillin, polymyxin B, quinupristin, retaparin, rifampin, streptomycin, sulfacetamide, sulfadiazine, sulfadiazine, sulfamethoxazole, sulfasalazine, sulfasalazine, teicoplanin, tervacancin, tetracycline, tigecycline, tobramycin, trimethoprim, or vancomycin, or combinations thereof. In some embodiments, the drug compound is an anticoagulant or thrombolytic agent. In some embodiments, the anticoagulant or thrombolytic agent includes alteplase, argatroban, bivalirudin, fondaparinux sodium, lepirudine, streptokinase, or urokinase, or combinations thereof, or two or more thereof. In some embodiments, the pharmaceutical compound is an antifungal agent. In some embodiments, the antifungal agent includes azole antifungal agents. In some embodiments, the antifungal agent includes albendazole, clotrimazole, econazole, fluconazole, isaconazole, itraconazole, ketoconazole, miconazole, posaconazole, tebuconazole, thiabendazole, or voriconazole, or combinations thereof, or two or more thereof. In some embodiments, the antifungal agent is amphotericin B, anisofungin, caspofungin, flucytosine, micafungin, etc.Natamycin or voriconazole, or combinations thereof, or two or more thereof. In some embodiments, the pharmaceutical compound is an antitumor drug. In some embodiments, the antitumor drug is afatinib, alectinib, aristetinib, axitinib, bosutinib, cabozantinib, canenatinib, carfilzomib, sildenafil, ceritinib, cimetidine, cobitinib, dabrafenib, darazabine, dasatinib, decarsetinib, dovitinib, erlotinib, etorcoxib, feranib, grelasatinib, ibrutinib, ederalipix, imatinib, ispinib, ixazomib, lapatinib, lenvatinib, lincitinib, etc. Lonafanib, masatitinib, motishanib, nilotinib, nintedanib, odandarbitril, olaparib, onasipexole, osimertinib, palbociclib, pazopanib, peritinib, ponatinib, regorafenib, renalapade, ruxolitinib, celicillinib, sorafenib, sunitinib, tandutinib, tepififib, tofacitinib, vandetanib, varititinib, varititinib, valproicinib, veripabib, vemectinib, vemodendabib, or combinations thereof, or two or more thereof. In some embodiments, the drug compound is an antiviral agent. In some implementation schemes, antiviral agents include abacavir, acyclovir, adefovir, amantadine, ampravir, atazanavir, bicretiravir, cidofovir, darunavir, dasabuvir, deraviridine, norinosine, dolutegravir, efavirenz, erteiravir, emtricitabine, enfuvirtide, entecavir, famciclovir, foscarnet, ganciclovir, grazoprevir, imiquimod, indinavir, lamivudine, and others. Lanimivir, ledipasvir, lopinavir, maraviro, nalfinavir, nevirapine, olbitasvir, oseltamivir, pariravir, penciclovir, peramivir, praxavir, podophyllotoxin, raltegravir, ribavirin, rilpivirine, ritonavir, saquinavir, sofosbuvir, stavudine, tenofovir, telanavir, trifluuridine, valacyclovir, valganciclovir, zanamivir, or zidovudine, or combinations thereof. In some embodiments, the pharmaceutical compound includes a cardiovascular drug. In some embodiments, the cardiovascular drug includes brombenzylamine, dobutamine, dopexamine, eprostol, esmolol, iloprost, nesiritide, nitroglycerin, norepinephrine, or phenylephrine, or combinations thereof, or two or more of them. In some embodiments, the pharmaceutical compound includes a central nervous system depressant. In some embodiments, central nervous system depressants include alprazolam, nitrazepam, clonazepam, diazepam, dexmedetomidine, dextromethorphan, flurazepam, gabapentin, ketamine, lorazepam, midazolam, oxazepam, propofol, temazepam, or triazolam, or combinations thereof, or two or more thereof. In some embodiments, the drug compound includes a central nervous system stimulant. In some embodiments, the central nervous system stimulant includes amphetamine, cocaine, dextromethorphan, dextroamphetamine, ephedrine, lysine amphetamine, methylamphetamine, methylphenidate, modafinil, phenylephrine, etc.The drug compound comprises pseudoephedrine or sibutramine, or combinations thereof, or two or more thereof. In some embodiments, the drug compound includes a local anesthetic. In some embodiments, the local anesthetic includes articaine, benzocaine, bupivacaine, chloroprocaine, cocaine, dibutylcaine, eticaine, levobupivacaine, lidocaine, malbifocaine, prilocaine, procaine, imicaine, ropivacaine, or tetracaine, or combinations thereof. In some embodiments, the drug compound includes an antiemetic. In some embodiments, the antiemetic includes dolasetron, granisetron, ondansetron, or palonosetron, or combinations thereof. In some embodiments, the drug compound is an anti-migraine. In some embodiments, the anti-migraine includes amotriptan, avitriptan, doniptriptan, eletriptan, fultriptan, lamitantan, nalatriptan, rizatriptan, sumatriptan, or zolmitriptan, or combinations thereof. In some embodiments, the pharmaceutical compound includes an anti-Parkinson's disease drug. In some embodiments, the anti-Parkinson's disease drug includes amantadine, apomorphine, benzalkonium chloride, bromhexine, cabergoline, carbidopa, entacapone, foscarbidopa, foscarbidopa, levodopa, levodopa, melevodin, pramipexole, rasagiline, ropinirole, rotigotine, safenamide, selegiline, tocapone, or trihexyphenidyl, or combinations thereof. In some embodiments, the pharmaceutical compound includes an antihistamine. In some embodiments, the antihistamine includes avastin, bromophenamine, cetirizine, chlorpheniramine, clomastine, cyproheptadine, desloratadine, dextrochlorpheniramine, diphenhydramine, doxylamine, fexofenadine, hydroxyzine, levocetirizine, loratadine, meclomethasone, promirtine, or tropineamine, or combinations thereof. In some embodiments, the pharmaceutical compound includes 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 includes an opioid. In some embodiments, the opioid includes buprenorphine, butorphanol, codeine, fentanyl, heroin, hydrocodone, hydromorphone, levonorgestrel, pethidine, methadone, morphine, naloxone, naltrexone, nalmefenamic acid, oxycodone, oxymorphone, pentazocine, sufentanil, tapentadone, or tramadol, or a combination thereof, or two or more thereof. In some embodiments, the pharmaceutical compound is a tyrosine kinase inhibitor. In some embodiments, the tyrosine kinase inhibitor includes bosutinib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, ponatinib, sorafenib, or sunitinib, or two or more thereof. In some implementations, the pharmaceutical compounds include amipyridine, amifostine, aminocaproic acid, argatroban, asenapine, atropine, bivalirudin, cisatracurium, deferoxamine, desmopressin, gabapentin, lurasidone, milrinone, nicotine, octreotide, pregabalin, rocuronium bromide, terbutaline, tirofiban, tranexamic acid, vecuronium bromide, and others.Napafenamide or any combination thereof.

[0006] In some aspects, this document provides a method for preparing a pharmaceutical composition comprising, in a suitable liquid medium, combining: a) a pharmaceutical compound or an enantiomer, mixture of enantiomers or isotopic variant thereof in a free basic form, wherein the pharmaceutical compound comprises at least one basic nitrogen atom and has a pKa of at least 1; and b) a complexing agent in a free acidic form 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 respects, this article provides methods for treating diseases or conditions, which include the administration of pharmaceutical compositions as described herein or pharmaceutically acceptable salts as described herein. Attached Figure Description

[0008] Figure 1A Showing with Na + and H + An exemplary structure of a complexed SBEBCD.

[0009] Figure 1B Examples showing the structure of tigecycline-SBEBCD salt.

[0010] Figure 2A Examples of fully dissolved rimantadine HCl formulations are shown.

[0011] Figure 2B Examples of incompletely dissolved rimantadine HCl formulations are shown.

[0012] Figure 2C Examples showing the structure of rimantaline-SBEBCD salt.

[0013] Figure 3A Display relative to H + An example of undissolved midazolam SBEBCD-acid in a 1:1 ratio is shown in the turbid solution.

[0014] Figure 3B Examples showing a 3:1 ratio of midazolam SBEBCD-acid to completely dissolved cyclodextrin are illustrated in the clear solution.

[0015] Figure 3C This shows an example of midazolam SBEBCE-acid 3:1 salt, which was freeze-dried and then pulverized into a grayish-white powder.

[0016] Figure 4 Examples showing the structure of a hydrocortisone predrug-SBEBCD salt having a non-ionized hydrocortisone predrug in the complexation pores.

[0017] Figure 5AImages showing a solid containing sodium hydroxide and SBEBCD (Cap) in a 6.5:1 molar ratio on day 1 after lyophilization, followed by 21 days of exposure to air, and then incubation at 40°C.

[0018] Figure 5B Images showing solids containing sodium hydroxide and SBEBCD (Cap) in a 5:1 molar ratio on day 1 after lyophilization, followed by 21 days of exposure to air, and then incubation at 40°C.

[0019] Figure 5C Images showing solids containing sodium hydroxide and SBEBCD (Cap) in a 3:1 molar ratio on day 1 after lyophilization, followed by 21 days of exposure to air, and then incubation at 40°C.

[0020] Figure 5D Images showing solids containing sodium hydroxide and SBEBCD (Cap) in a 1:1 molar ratio on day 1 after lyophilization, followed by 21 days of exposure to air, and then incubation at 40°C.

[0021] Figure 5E Images showing solids containing SBEBCD (Cap) in a 1:1 molar ratio on day 1 after freeze-drying, followed by 21 days of exposure to air, and then incubation at 40°C.

[0022] Figure 6 The image shows ziprasidone (70 mg / mL) SBEBCD-acid at a 6:1 ratio in a 5 mL volume after stirring for 1 hour, with the solid adhering to the side of the vial.

[0023] Figure 7 The image shows ziprasidone (70 mg / mL) SBEBCD-acid at a 6:1 ratio in a 5 mL volume after stirring for 1 hour, with the solid adhering to the bottom of the vial.

[0024] Figure 8 The image shows ziprasidone (70 mg / mL) SBEBCD-acid at a 6:1 ratio in a 5 mL volume after stirring for 1 hour, showing the solid after being scraped from the side of the vial and resuspended in the solution.

[0025] Figure 9 The image shows ziprasidone (70 mg / mL) SBEBCD-acid in a 4:1 ratio at a 5 mL scale after initial stirring, with the solid suspended in the solution.

[0026] Figure 10 The image shows ziprasidone (70 mg / mL) SBEBCD-acid at a 4:1 ratio in a 5 mL volume after stirring for 1 hour, with the solid adhering to the side of the vial.

[0027] Figure 11The image shows ziprasidone (70 mg / mL) SBEBCD-acid at a 4:1 ratio in a 5 mL volume after stirring for 1 hour, with the solid adhering to the bottom of the vial.

[0028] Figure 12 The image shows ziprasidone (70 mg / mL) SBEBCD-acid in a 4:1 ratio at a scale of 5 mL after stirring for 1 hour, showing the solid after being scraped off the side of the vial and resuspended in the solution.

[0029] Figure 13 The image shows a solution of 70 mg / mL ziprasidone SBEBCD-acid at a ratio of 4:1, in 1 mL volume and stirred for 10 minutes, with solids adhering to the sides and bottom of the vial.

[0030] Figure 14 A solution of 70 mg / mL ziprasidone SBEBCD-acid at a ratio of 4:1 is shown in 1 mL volume and stirred for 10 minutes, showing a clear solution separated from the undissolved solids at pH 0.93.

[0031] Figure 15 The image shows a 14 mg / mL ziprasidone SBEBCD-acid 4:1 solution in 5 mL volume and stirred for 22 minutes, showing a clear solution and solids adhering to the bottom of the vial after scraping the solids off from the side.

[0032] Figure 16 The image shows a solution of 11.7 mg / mL ziprasidone SBEBCD-acid at a ratio of 4:1, in 6 mL volume and stirred for 25 minutes. It is a turbid solution with small suspended particles and solids adhering to the bottom of the vial.

[0033] Figure 17 The image shows a solution of 8.75 mg / mL ziprasidone SBEBCD-acid at a ratio of 4:1, in 8 mL volume and stirred for 31 minutes. It shows a turbid brownish solution and large solid lumps scraped from the bottom of the vial.

[0034] Figure 18 The image shows a solution of 7.8 mg / mL ziprasidone SBEBCD-acid at a ratio of 4:1, with the solids that were previously scraped off adhering to the bottom again, in a volume of 9 mL and stirred for 34 minutes.

[0035] Figure 19 The image shows a solution of 5.4 mg / mL ziprasidone SBEBCD-acid at a ratio of 4:1, in 13 mL volume and stirred for 46 minutes. The solution is a brownish-yellow turbidity, with solids adhering to the bottom of the vial and the crease between the bottom and the side.

[0036] Figure 20The image shows a solution of 5 mg / mL ziprasidone SBEBCD-acid at a ratio of 4:1, in 14 mL volume and stirred for 65 hours, showing a clear solution and solids adhering to the bottom of the vial.

[0037] Figure 21 The image shows a solution of 70 mg / mL ziprasidone SBEBCD-acid at a ratio of 6:1, in 1 mL volume and stirred for 10 minutes, with solids adhering to the sides and bottom of the vial.

[0038] Figure 22 A solution of 17.5 mg / mL ziprasidone SBEBCD-acid at a ratio of 6:1 is shown in 4 mL volume and stirred for 19 minutes, showing solids that adhered to the sides and bottom of the vial and were then scraped off from the sides.

[0039] Figure 23 The image shows a solution of 14 mg / mL ziprasidone SBEBCD-acid at a ratio of 6:1, in 5 mL volume and stirred for 22 minutes. Small particles are shown suspended in the solution, as well as solids that adhere to the bottom of the vial.

[0040] Figure 24 The image shows a solution of 7.8 mg / mL ziprasidone SBEBCD-acid at a ratio of 6:1, in 9 mL volume and stirred for 34 minutes. Large clumps are suspended in the solution, and solids adhere to the bottom of the vial.

[0041] Figure 25 A solution of 5.4 mg / mL ziprasidone SBEBCD-acid at a ratio of 6:1 is shown in 13 mL volume and stirred for 46 minutes, showing large clumps suspended in the solution.

[0042] Figure 26 The image shows a solution of 5 mg / mL ziprasidone SBEBCD-acid at a ratio of 6:1, in 14 mL volume and stirred for 24 hours, with solids adhering to the bottom of the vial.

[0043] Figure 27 A table showing solutions with various SBEBCD salt concentrations N=1 (after 3 weeks of incubation) with and without Fehling's reagent is presented. Detailed Implementation

[0044] This document provides, for example, compositions comprising a pharmaceutical compound salt and a chelating agent as an anti-counterionic agent. These salts can be used in a variety of pharmaceutical compositions, including those for reducing irritation to tissues and / or skin, subcutaneous, intramuscular, intranasal, and sublingual formulations. In some aspects, the use of the salts provided herein in subcutaneous, intranasal, or sublingual formulations is associated with reduced tissue irritation at the site of application and increased solubility and bioavailability. In some aspects, compositions comprising a pharmaceutical compound having a basic nitrogen atom in a low molar ratio with a chelating agent are formulated for subcutaneous, sublingual, or intranasal administration. In some aspects, compositions comprising a prodrug pharmaceutical compound having a basic nitrogen atom are formulated for subcutaneous, sublingual, or intranasal administration. In some aspects, compositions comprising ionized and unionized pharmaceutical compounds are formulated for subcutaneous, sublingual, or intranasal administration. This document also provides, for example, methods for treating, preventing, or managing viral infections, bacterial infections, fungal infections, autoimmune disorders, inflammatory disorders, depression or opioid overdose, mental disorders, cognitive impairment, neurological disorders, and various other disorders.

[0045] definition The abbreviations used in this article have their conventional meanings in the fields of chemistry and biology. The chemical structures and formulas described in this article are constructed according to the standard rules of chemical valence known in the field of chemistry.

[0046] When substituents are specified by their conventional chemical formula written from left to right, they also cover chemically identical substituents produced by writing the structure from right to left, for example, -CH2O is equivalent to -OCH2-.

[0047] As used herein, the term "about" refers to the degree of variation permitted for a value or range, such as within 10% or 5% of the said limits of the value or range. Unless otherwise stated, "about" means the degree of variation within 10% of the said limits of the value or range.

[0048] As used herein, the term "pharmaceutical compound" and similar terms refer to any compound that has the potential to be administered to a subject and can impart any type of therapeutic benefit to the subject, such as treating or preventing a disease, alleviating symptoms of a disease or condition, or for any purpose for which a drug or pharmaceutical product may be used. Typically, these compounds will be small organic molecules, although other compounds (such as peptides) are also considered pharmaceutical compounds as used herein. In embodiments, pharmaceutical compounds will contain a basic nitrogen atom (e.g., an amino group) that can be protonated upon interaction with an acidic functional group such as a carboxylic acid or sulfonic acid. When referring to pharmaceutical compositions, these compounds may generally be referred to as "active pharmaceutical ingredient" or "API". In some cases, pharmaceutical compounds herein may simply be referred to as "compounds".

[0049] The terms “opioid drug compound,” “opioid drug,” or “opioid,” and similar terms are all used interchangeably and, unless otherwise specified, each term has the same meaning. The terms may refer to any naturally occurring opioid or any synthetic homologue or analogue. Additionally, it is intended to include any synthetic compound having similar biological activity to the opioid receptor of the target, and any compound having opioid antagonist activity (e.g., naltrexone or naloxone). In some cases, the pharmaceutical composition or its method of manufacture or use does not include naloxone. When referring to pharmaceutical compositions, these compounds may generally be referred to as “active pharmaceutical ingredient” or “API.”

[0050] As used herein, the terms “comprising / comprises” and the like are used in their typical meaning, departing from any claim or embodiment, where the use of such language allows for the inclusion of additional elements, components, or features. However, it is also contemplated that in each formulation, salt, method, or other disclosure provided herein using the term “comprising,” the formulation, salt, method, or other disclosure may not involve additional elements, components, or features, just as the term “composes of” is used in its place. Furthermore, it is also contemplated that the term “comprising” or similar terms may be replaced in the same manner as the term “substantially constitutes”.

[0051] As used herein, “molar equivalent” refers to a comparison of the number of moles of one substance to the number of moles of another substance, and reflects that the comparison should be on a molar or molar concentration basis (e.g., the ratio of the number of moles of one compound to the number of moles of another compound). Molar equivalents need not be integer values. For example, an embodiment of a pharmaceutical composition containing a substance of “molar equivalent” indicates that the amount of substance present will be measured in some molar concentration descriptor, such as an additional equivalent of 0.001 to 100 molar equivalents of the substance, or any other range specified herein.

[0052] Unless otherwise stated, all percentage components are given as weight percentages.

[0053] Unless otherwise stated, all average molecular weights of polymers are weight-average molecular weights.

[0054] As used in this article, “individual” (as in the context of treatment) refers to both mammals and non-mammals. Mammals include, for example, humans; non-human primates, such as apes and monkeys; and non-primate animals, such as dogs, cats, cows, horses, sheep, and goats. Non-mammals include, for example, fish and birds.

[0055] The terms "disease," "symptom," or "condition" refer to a state or health condition of a patient or subject that can be treated with the compounds or methods provided herein. A disease can be a physical disorder. A disease can be a mental or psychiatric disorder. A disease can be an infection, such as a viral, bacterial, or fungal infection. A disease can be an autoimmune disease. A disease can be a mood disorder. A disease can be an inflammatory disease. A disease can be a brain tumor. A disease can be a neurological condition or disorder. A disease can be a migraine. A disease can be pancreatitis. A disease can be lymphoma. A disease can be an opioid overdose. A disease can be influenza. In some further instances, “mental or psychiatric disorder” refers to human mental or psychiatric disorders, including major depressive disorder, treatment-resistant major depressive disorder, suicidal tendencies, suicidal ideation, dysphoric mood, type I bipolar disorder, type II bipolar disorder, post-traumatic stress disorder (PTSD), complex trauma, anorexia nervosa, bulimia nervosa, eating disorder (NOS), obsessive-compulsive disorder, substance-related disorders (e.g., cannabis dependence or withdrawal, barbiturate dependence or withdrawal, benzodiazepine dependence or withdrawal, amphetamine dependence or withdrawal, opioid dependence or withdrawal, opioid dependence or detoxification, alcohol dependence or withdrawal, cocaine dependence or withdrawal), pain disorders and inflammatory disorders, pain management (including but not limited to neuropathic pain), complex regional pain syndrome, and postherpetic neuralgia. In some further instances, “neurological disease or condition” refers to human neurological diseases or conditions, 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, herpes zoster, shingles, radiculopathy, polyneuropathy, movement disorder, 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, depression, complex trauma, anorexia nervosa, bulimia nervosa, eating disorder (NOS), obsessive-compulsive disorder, intermittent fulminant disorder, sleep disorder, pain disorder, or inflammatory disorder. In some further instances, the brain tumor may be an acoustic neuroma, astrocytoma, brain metastasis, choroid plexus carcinoma, craniopharyngioma, embryonal tumor, ependymoma, glioblastoma, glioma, medulloblastoma, meningioma, oligodendroglioma, pediatric brain tumor, pineal-blastoma, or pituitary tumor. In some cases, the disease, symptom, or condition is one associated with substantial or significant pain. In some aspects, the subject is given a salt of the preparations described herein to control pain. The pain may be associated with a suitable condition for which an opioid pain management protocol is acceptable. In some aspects, the subject is given a salt of the preparations described herein to treat a brain tumor.In some respects, the administration of salts of the following formulations to a subject is used to treat brain tumors: pharmaceutical compounds having a basic nitrogen atom, including dissociative pharmaceutical compounds, dissociative hallucinogen compounds, dissociative anesthetic compounds, arylcyclohexylamine, 1,2-diarylethylamine, keto-arylcyclohexylamine, or compounds that modulate NMDA receptors, ketamine, ketamine derivatives or analogs, methoxetamine, dechlorinated ketamine, N-ethyldechlorinated ketamine (eticyclidone), 3-methoxyphencyclidine, methoxieticyclidine, ephenidine, lanicemine, dextromethorphan, dextrophene, or methoxyketamine.

[0056] When used to describe treatment for an individual with a disorder, the term "effective amount" refers to the amount of the compound described herein that effectively inhibits or otherwise acts on the relevant receptor in the individual's tissues, wherein such inhibition or other action occurs to a degree sufficient to produce a beneficial therapeutic effect. Effective amounts will vary based on the pharmaceutical compound (including, but not limited to, opioids or other APIs used in the formulation) and the indication intended to be treated with said compound (including, but not limited to, opioids or other APIs).

[0057] As used herein, the term "substantially" means completely or nearly completely. For example, a composition that is "substantially free" of a component either contains no component or contains trace amounts such that any relevant functional properties of the composition are unaffected by the presence of those trace amounts. For example, a compound that is "substantially pure" contains only negligible trace impurities.

[0058] All chiral, diastereomer, and / or racemic forms of the structure are intentional unless a specific stereochemical or isomeric form is specifically indicated. The compounds described herein may include optical isomers enriched or resolved at any or all asymmetric atoms, as is apparent from the description, at any enrichment level. Racemic mixtures and diastereomer mixtures, as well as individual optical isomers, may be isolated or synthesized to be substantially free of their enantiomers or diastereomer conjugates, and these are all within the scope of this disclosure.

[0059] The isotopic forms of one or more atoms in a molecule that differ from the isotopic distribution of naturally occurring atoms are called the molecule's "isotopic labeling form." All isotopic forms of atoms are included as options in the composition of any molecule unless a specific isotopic form of the atom is specified. For example, any hydrogen atom or set thereof in a molecule can be any isotopic form of hydrogen, such as any combination of protium (…). 1 H), deuterium ( 2 H) or tritium ( 3H). Similarly, any carbon atom or set thereof in a molecule can be any isotopic form of carbon, such as 11 C 12 C 13 C or 14 C, or any nitrogen atom or set thereof in the molecule, can be any isotopic form of nitrogen, such as 13 N、 14 N or 15 N. A molecule can include any combination of isotopic forms in the constituent atoms that make up the molecule, and the isotopic form of each atom that makes up the molecule is chosen independently. In a multimolecular sample of a compound, not every individual molecule must have the same isotopic composition. For example, a sample of a compound can include molecules containing a variety of different isotopic compositions, such as in tritium or 14 In C-labeled samples, only a portion of the molecular composition of the macroscopic sample contains radioactive atoms. It should also be understood that many elements, which are not artificially enriched isotopes, are mixtures of naturally occurring isotopic forms, such as... 14 N and 15 N、 32 S and 34 S, etc. The molecules described herein are defined as including the isotopic forms of all their constituent elements at every position in the molecule. As is well known in the art, isotopically labeled compounds can be prepared by conventional methods of chemical synthesis, except by substituting the isotopically labeled precursor molecule. Radiolabeled or stable isotopes can be obtained by any method known in the art, such as by neutron absorption of precursor nuclides in a nuclear reactor, by cyclotron reaction, or by isotope separation, such as by mass spectrometry. The isotopic form is incorporated into the precursor as needed for any particular synthetic route. For example, it can be prepared using neutrons generated in a nuclear reactor. 14 C and 3 H. After nuclear transformation, 14 C and 3 H is incorporated into the precursor molecule, and then further processed as needed.

[0060] A “hydrate” is a compound present in a composition along with water molecules. A composition may include stoichiometric amounts of water, such as monohydrate or dihydrate, or may include random amounts of water. As used herein, the term “hydrate” refers to a compound in solid form, such as in an aqueous solution, although it may be hydrated rather than a hydrate as used herein.

[0061] "Solvate" is a similar composition, except that a solvent other than water is used instead of water. For example, methanol or ethanol can form an "alcohol," which can also be stoichiometric or non-stoichiometric. As used herein, the term "solvent" refers to a solid form, such as a solution of a compound in a solvent, which, although it can be solvated, is not a solvate as used herein.

[0062] "Prodrugs," as well known in the art, are substances that can be administered to a patient, wherein the substance is converted into an active pharmaceutical ingredient in the body by the action of biochemicals in the patient's body, such as enzymes. Examples of prodrugs include esters with a carboxylic acid group, which can be hydrolyzed by endogenous esterases found in the bloodstream of humans and other mammals. Other examples of prodrugs include boronic acid esters, which can be hydrolyzed under physiological conditions to provide the corresponding boronic acid. Conventional procedures for selecting and preparing suitable prodrug derivatives are described, for example, in "Design of Prodrugs," ed. H. Bundgaard, Elsevier, 1985.

[0063] In various implementations, compounds as shown in any embodiment or exemplary compound are provided.

[0064] The conditions attached may apply to any disclosed category or implementation, wherein any one or more other disclosed implementations or types may be excluded from those categories or implementations.

[0065] Isomerism of the compounds described in this article Optical heterogeneity It should be understood that when the compounds of this disclosure contain one or more chiral centers, the compounds may exist as pure enantiomers or diastereomers or as racemic mixtures, and may be isolated as pure enantiomers or diastereomers or as racemic mixtures. Therefore, this disclosure includes any possible enantiomers, diastereomers, racemates, or mixtures thereof of the compounds described herein.

[0066] Isomers arising from the presence of a chiral center comprise a pair of non-overlapping isomers called "enantiomers." A single enantiomer of a pure compound is optically active; for example, it can rotate the plane of plane-polarized light. According to... Cahn-Ingold-Prelog The system assigns a single enantiomer. Substituent priorities are ordered based on atomic weight, with higher priority groups assigned by the system program. Once the priorities of the four groups are determined, the molecule is oriented such that the lowest-ranking group points away from the observer. Then, if the descending order of other groups proceeds clockwise, the molecule is assigned as (…). R If the descending order of other groups is counterclockwise, then the molecule is designated as ( SIn the examples below, Cahn-Ingold-Prelog The order is A > B > C > D. The lowest-ranking atom, D, is oriented away from the observer. (R) configuration (S) configuration This disclosure is intended to cover diastereomers, as well as their racemic and resolved diastereomeric and enantiomeric pure forms and their salts. Diastereomer pairs can be resolved by known separation techniques, including normal-phase and reversed-phase chromatography, and crystallization.

[0067] "Separated optical isomer" means a compound that has been substantially purified from its corresponding optical isomer of the same formula. By weight, the separated isomer is at least about 80% pure, more at least 90% pure, even more at least 98% pure, and at most at least about 99% pure.

[0068] The isolated optical isomers can be purified from racemic mixtures using known chiral separation techniques. According to one such method, racemic mixtures of the compounds described herein or their chiral intermediates are purified by HPLC using a suitable chiral column (e.g., DAICEL). ® CHIRALPAK ® The column (a member of the series) is separated into 99 wt% pure optical isomers (Daicel Chemical Industries, Ltd., Tokyo, Japan). The column is operated according to the manufacturer's instructions.

[0069] Certain compounds disclosed herein have asymmetric carbon atoms (optical or chiral centers) or double bonds; enantiomers, racemates, diastereomers, tautomers, geometric isomers, stereoisomers (which may be defined by absolute stereochemistry as (R)- or (S)- or (D)- or (L)- of amino acids), and individual isomers are covered within the scope of this invention. The compounds disclosed herein do not include those known in the art to be too unstable to synthesize and / or isolate. This disclosure is intended to include compounds in racemic and optically pure forms. Optically active (R)- and (S)- or (D)- and (L)- isomers can be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. When the compounds described herein contain an alkene bond or other geometrically asymmetric centers, the compounds are intended to include E and Z geometric isomers unless otherwise stated.

[0070] As used herein, the term "isomer" refers to a compound having the same number and type of atoms and therefore the same molecular weight but different in terms of the arrangement or configuration of the atoms.

[0071] As used in this article, "tautomer" refers to one of two or more structural isomers that exist in equilibrium and are readily transformed from one isomer to another.

[0072] It will be apparent to those skilled in the art that certain compounds of this disclosure may exist in tautomeric forms, and all such tautomeric forms of the compounds are within the scope of this disclosure.

[0073] Unless otherwise stated, the structures depicted herein are intended to include all stereochemical forms of the structure; for example, the R and S configurations of each asymmetric center. Therefore, single stereochemical isomers of the compounds of the present invention, as well as mixtures of enantiomers and diastereomers, are within the scope of this disclosure.

[0074] "Alkyl" refers to a straight-chain or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms, which may optionally be unsaturated, has one or more double or triple bonds, and has 1 to 15 carbon atoms (i.e., C1-C1). 15 Alkyl group. In some embodiments, the alkyl group comprises one to six carbon atoms (i.e., C1-C6 alkyl). In some embodiments, the alkyl group is selected from methyl, ethyl, 1-propyl (n-propyl), 1-methylethyl (isopropyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (isobutyl), 1,1-dimethylethyl (tert-butyl), and 1-pentyl (n-pentyl). The alkyl group is attached to the rest of the molecule by a single bond. Unless otherwise stated, the term "alkyl" and its equivalents cover straight-chain, branched, and / or cyclic alkyl groups. In some cases, "alkyl" comprises cyclic and acyclic (straight-chain and / or branched) alkyl components.

[0075] The term "substituted" refers to a portion of a substituent on one or more carbon or heteroatoms that has a substituted structure. It should be understood that "substituted" or "replaced by" implies the condition that the substitution is consistent with the permissible valence of the substituted atom and the substituent, and that the substitution produces a stable compound, for example, one that does not spontaneously undergo transformation, such as through rearrangement, cyclization, elimination, etc. As used herein, the term "substituted" is envisioned to include all permissible substituents in organic compounds. In a broad sense, permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents in organic compounds. For suitable organic compounds, permissible substituents can be one or more and can be the same or different.

[0076] Substituents may include any substituent, such as halogen, hydroxyl, carbonyl (e.g., oxo (=O), carboxyl, alkoxycarbonyl, formyl or acyl), thiocarbonyl (e.g., thio (=S), thioester, thioacetate or thiocarbamate), alkoxy, phosphoryl, phosphate, phosphonate, phosphonite, amino, amide, amidine, imine, oximo, hydrazine, cyano, nitro, azide, mercapto, alkyl, alkylthio, sulfate, sulfonate, aminosulfonyl, sulfinylamino, sulfonyl, aralkyl, carbocyclic, heterocyclic, cycloalkyl, heterocyclic alkyl, aromatic and heteroaromatic moieties.

[0077] As used herein, "acidic functional group" or similar terms (e.g., "acidic functional group") refer to a chemical moiety of a conjugate base (e.g., a deprotonated anion) containing at least one dissociable proton (or an isotopic variant thereof) or an acidic functional group. In some embodiments, the dissociable proton dissociates from the chemical moiety at pH values ​​common in aqueous systems (e.g., from about 1 to about 14). In some embodiments, the dissociable proton dissociates from the chemical moiety in aqueous systems with pH values ​​less than 7 (e.g., pKa values ​​less than 7, such as pKa less than 6, less than 5, less than 4, less than 3, less than 2, or less than 1). As will be understood by those skilled in the art, whether an acidic functional group contains a 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 molecules with acidic functional groups or the presence of any base molecules). Therefore, unless otherwise specified, the term “acidic functional group” (or a specific acidic functional group, such as a carboxylic acid or sulfonic acid) as used herein is intended to cover part of the protonated form, part of the deprotonated form, and part of any salt.

[0078] Unless otherwise stated, the structures described herein also mean compounds that differ only in the presence of one or more isotopically enriched atoms (e.g., isotopic variants). For example, in addition to hydrogen being replaced by deuterium or tritium, or carbon being... 13 C- or 14 Compounds having the structure of this invention, other than C-enriched carbon substitutions, are within the scope of this disclosure.

[0079] The compounds disclosed herein may also contain atomic isotopes in non-natural proportions at one or more atoms constituting such compounds. For example, the compounds may be radiolabeled with radioactive isotopes, such as tritium ( 3 H), Iodine-125 ( 125 I) or carbon-14 ( 14 C). All isotopic variants of the compounds disclosed herein, whether radioactive or not, are included within the scope of this disclosure.

[0080] As used herein, the term "a / an" means one or more species. Furthermore, the phrase "replaced by" as used herein means that a specified group may be replaced by one or more of the specified substituents. For example, when a group such as an alkyl or heteroaryl is "replaced by an unsubstituted C1-C..." 20 When alkyl or unsubstituted heteroalkyl groups of 2 to 20 members are substituted, the group may contain one or more unsubstituted C1-C1 groups. 20 Alkyl and / or one or more unsubstituted 2 to 20 heteroalkyl groups.

[0081] The term "salt" as known in the art includes organic compounds in ionic form that bind to counterions, such as carboxylic acids, sulfonic acids, or amines. For example, acids in their anionic form can form salts with: cations, such as metal cations, such as sodium, potassium, etc.; and with substances such as NH4+. + Ammonium salts or cations of various amines, including tetraalkylammonium salts such as tetramethylammonium, or other cations such as trimethylsulfonium. The terms "pharmaceutically acceptable salt" and / or "pharmacologically acceptable salt" mean salts comprising active compounds prepared with relatively non-toxic acids or bases, depending on the specific substituents found on the compounds described herein. When the compounds of this disclosure contain relatively acidic functional groups, base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired base (pure or in a suitable inert solvent). Examples of pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amino, or magnesium salts or similar salts. When the compounds of this disclosure contain relatively basic functional groups, acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired acid (pure or in a suitable inert solvent). Examples of pharmaceutically acceptable acid addition salts include those derived from inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, carbonic acid, monohydrocarbonic acid, phosphoric acid, monohydrophosphoric acid, dihydrophosphoric acid, sulfuric acid, monohydrosulfuric acid, hydroiodic acid, or phosphorous acid; and those derived from relatively non-toxic organic acids such as acetic acid, propionic acid, isobutyric acid, maleic acid, malonic acid, benzoic acid, succinic acid, succinic acid, fumaric acid, lactic acid, mandelic acid, phthalic acid, benzenesulfonic acid, p-toluenesulfonic acid, citric acid, tartaric acid, oxalic acid, and methanesulfonic acid. Also included are salts of amino acids such as arginine salts, and salts of organic acids such as glucuronic acid or galacturonic acid (see, for example, Berge et al., “Pharmaceutical Salts”). Journal of Pharmaceutical Science , 1977, 66 (1-19). Certain specific compounds of this disclosure contain both basic and acidic functional groups, which allow the compounds to be converted into base or acid addition salts.

[0082] Therefore, the compounds of this disclosure can exist as salts, such as salts formed with pharmaceutically acceptable acids. This disclosure includes such salts. Non-limiting examples 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, as well as quaternary ammonium salts (e.g., methyl iodide, ethyl iodide, etc.). These salts can be prepared by methods known to those skilled in the art.

[0083] The neutral form of the compound is regenerated by contacting the salt with a base or acid and separating the parent compound in a 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 some embodiments, the compounds of this disclosure contain basic and acidic functional groups, which allow the compound to be converted into a base addition salt or an acid addition salt. The neutral form of the compound can be regenerated by contacting the salt with a base or acid and separating the parent compound in a conventional manner. The parent form of the compound differs from the various salt forms in certain physical properties, such as solubility in polar solvents; however, unless specifically indicated, the salts disclosed herein are equivalent to the parent form of the compound for the purposes of this disclosure.

[0084] In addition to salt forms, this disclosure provides compounds in prodrug form. The prodrugs of the compounds described herein are those compounds that readily undergo chemical changes under physiological conditions to provide the compounds of this disclosure. The prodrugs of the compounds described herein can be converted in vivo after administration. Additionally, the prodrugs can be converted into the compounds of this disclosure in an in vitro environment by chemical or biochemical methods, for example, upon contact with suitable enzymes or chemical reagents.

[0085] Certain compounds of this disclosure may exist in both solvated and solvated forms (including hydrated forms). Generally, solvated forms are equivalent to unsolvated forms and are covered within the scope of this disclosure. Certain compounds of this disclosure may exist in a variety of crystalline or amorphous forms. Generally, all physical forms are equivalent to the intended use of this disclosure and are intended to be within the scope of this disclosure.

[0086] "Pharmaceutically acceptable excipients" and "pharmaceutically acceptable carriers" refer to substances that facilitate the administration of a compound to a subject and its absorption by the subject, and can be included in the compositions of this disclosure without causing significant adverse toxicological effects on the patient. Non-limiting examples of pharmaceutically acceptable excipients include water, NaCl, aqueous saline solutions, lactated Ringer's solution, ordinary sucrose, ordinary glucose, complexing agents (e.g., cyclodextrin), binders, fillers, disintegrants, lubricants, coatings, sweeteners, flavorings, salt solutions (e.g., Ringer's solution), alcohols, oils, gelatin, carbohydrates (e.g., lactose, amylose, or starch), fatty acid esters, hydroxymethyl cellulose, polyvinylpyrrolidone, and colorants, etc. Such formulations can be sterile and, if desired, mixed with adjuvants such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts affecting osmotic pressure, buffers, colorants, and / or aromatic substances, which do not react harmfully with the compounds of this disclosure. Those skilled in the art will recognize that other pharmaceutical excipients may be used in this disclosure.

[0087] The term "formulation" is intended to include an active compound and an encapsulating material as a carrier, which provides a capsule in which the active component, with or without another carrier, is surrounded by the carrier, and the carrier is thus bound to it. Similarly, it includes capsules and tablets. Tablets, powders, capsules, pills, capsules, and tablets can be used as solid dosage forms suitable for oral administration.

[0088] The term "treatment" refers to any indication of successful or improved injury, disease, pathology, or symptom, including any objective or subjective parameter such as relief; alleviation; reduction of symptoms or increased patient tolerance to the injury, pathology, or symptom; slowing of the rate of degeneration or decline; making the endpoint of degeneration less debilitating; or improving the patient's physical or mental health. Treatment or improvement of symptoms may be based on objective or subjective parameters, including the results of physical examination, neuropsychiatric examination, and / or psychiatric evaluation. The term "treatment" and its variations may include prevention of injury, pathology, symptom, or disease. In some implementations, treatment is prevention. In some implementations, treatment does not include prevention.

[0089] As used herein, “treating” (and as is known in the art) also broadly includes any method that achieves a beneficial or desired outcome (including clinical outcomes) in the subject’s condition. Beneficial or desired clinical outcomes may include, but are not limited to, relief or improvement of one or more symptoms or conditions, reduction of disease severity, stabilization (e.g., non-exacerbation) of the disease state, prevention of the spread or diffusion of the disease, delay or slowing of disease progression, improvement or relief of the disease state, reduction of disease relapse, and partial or complete remission, detectable or undetectable. In other words, as used herein, “treatment” includes any cure, improvement, or prevention of disease. Treatment may prevent the onset of disease; inhibit the spread of disease; relieve symptoms of disease (e.g., eye pain, halo, red eye, very high intraocular pressure), completely or partially eliminate the underlying cause of disease, shorten the duration of disease, or a combination of these. Related symptoms will vary depending on the intended indication for the specific API.

[0090] As used herein, “treatment” includes preventative treatment. Treatment methods include administering a therapeutically effective amount of the compound described herein to a subject. Administration may consist of a single administration or may include a series of administrations. The length of treatment depends on various factors, such as the severity of the condition, the patient's age, the concentration of the compound, the activity of the composition used for treatment, or combinations thereof. It will also be appreciated that the effective dose of the agent used for treatment or prevention may be increased or decreased during a particular treatment or prevention regimen. Changes in dose can be produced and become apparent by standard diagnostic assays known in the art. In some cases, prolonged administration may be required. For example, administering the composition to a subject in an amount and for a duration sufficient to treat the patient.

[0091] The term "prevention" refers to reducing the occurrence of disease symptoms in patients. As mentioned above, prevention can be complete (no detectable symptoms) or partial, resulting in fewer observed symptoms than would be present without treatment. In some implementations, prevention refers to slowing the progression of a disease, disorder, or symptom or inhibiting its progression into a harmful or otherwise undesirable state.

[0092] "Patient" or "subject in need" means a living organism that suffers from or is susceptible to a disease or condition that can be treated by administration of the pharmaceutical compositions provided herein. Non-limiting examples include humans, other mammals, cattle, rats, mice, dogs, monkeys, goats, sheep, cattle, deer, and other non-mammals. In some embodiments, the patient is a human.

[0093] "Effective amount" is an amount sufficient, relative to the absence of the compound, for the compound to achieve its stated purpose (e.g., to achieve the effect of its administration, to treat a disease, to reduce enzyme activity, to increase enzyme activity, to reduce signal transduction pathways, or to reduce one or more symptoms of a disease or condition). An example of an "effective amount" is an amount sufficient to help treat, prevent, or reduce one or more symptoms of a disease; it may also be referred to as a "therapeutic effective amount." "Relief" (and its grammatical equivalent) of one or more symptoms refers to a reduction in the severity or frequency of one or more symptoms, or the elimination of one or more symptoms. A "preventive effective amount" of a drug is an amount of drug that, when administered to a subject, will have the intended preventive effect, such as preventing or delaying the onset (or recurrence) of an injury, disease, pathology, or condition, or reducing the likelihood of the onset (or recurrence) of an injury, disease, pathology, or condition or its symptoms. Complete prevention does not necessarily occur with a single dose and may occur only after a series of doses. Therefore, a preventive effective amount may be administered in one or more doses. As used herein, "activity reduction amount" refers to the amount of antagonist required to reduce enzyme activity relative to the absence of an antagonist. As used herein, “the amount of antagonist required to disrupt the function of an enzyme or protein, relative to the absence of an antagonist. The exact amount will depend on the purpose of treatment and will be determined by someone skilled in the art using known techniques (see, for example, Lieberman). Pharmaceutical Dosage Forms (Volumes 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 (20th edition, 2003, Gennaro, Ed., Lippincott, Williams & Wilkins). Therapeutic effective doses can be determined by measuring relevant physiological effects and can be adjusted in conjunction with dosing regimens and diagnostic analyses of the patient's condition. For example, measuring serum levels of the inhibitor (or, for example, its metabolites) at a specific time after administration can indicate whether a therapeutically effective dose has been administered.

[0094] For any of the compounds described herein, the therapeutically effective amount can initially be determined from cell culture assays. Target concentrations will be those of the active compounds that, when measured using the methods described herein or methods known in the art, enable the effects of the methods described herein.

[0095] As is well known in the art, therapeutically effective doses for humans can also be determined from animal models. For example, human doses can be formulated to achieve concentrations found to be effective in animals. As described above, human doses can be adjusted by monitoring the effectiveness of the compound and by adjusting the dose upwards or downwards. Adjusting the dose based on the methods described above and other methods to achieve maximum efficacy in humans is entirely within the capabilities of a person skilled in the art. Adjusting the dose based on the methods described above and other methods to achieve maximum therapeutic window efficacy or toxicity in humans is entirely within the capabilities of a person skilled in the art.

[0096] As used herein, the term "therapeutic effective dose" refers to an amount of therapeutic agent sufficient to improve the condition as described herein. For example, for a given parameter, a therapeutic effective dose 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 an increase or decrease in "multiples." For example, the effect of a therapeutic effective dose can be at least 1.2 times, 1.5 times, 2 times, 5 times, or more than that of a control.

[0097] Dosage can vary depending on the patient's needs and the compound used. In the context of this disclosure, the dose administered to the patient should be sufficient to achieve a beneficial therapeutic response over time. The size of the dose will also be determined by the presence, nature, and extent of any adverse side effects. Determining the appropriate dose for a particular situation is within the scope of the practitioner's skill. Typically, treatment begins with a smaller dose than the optimal dose of the compound. Thereafter, the dose is increased in small increments until the optimal effect is achieved in the given environment. Dosage and intervals can be individually adjusted to provide levels of the administered compound effective for the specific clinical indication being treated. This will provide a treatment regimen commensurate with the severity of the individual's disease state.

[0098] As used herein, the term “application” refers to subcutaneous (i.e., “SC”, “subQ”, or “SQ”) administration, oral administration, administration as a suppository, local contact or application, intravenous, parenteral, intraperitoneal, intramuscular, intraosseous, intralesional, intrathecal, intracranial, intranasal, epidural, or implanted sustained-release device, such as a microosmotic pump. Application is via any route, including parenteral and transmucosal (e.g., buccal, sublingual, palatal, gingival, nasal, vaginal, rectal, transvaginal, or percutaneous). Parenteral administration includes, for example, intravenous, intramuscular, intraarterial, intradermal, subcutaneous, intraperitoneal, intravenous, and intracranial administration. Other delivery methods include, but are not limited to, the use of liposomal formulations, intravenous infusion, transdermal patches, etc. “Co-application” means that the composition described herein is administered simultaneously with, just before, or just after, the administration of one or more other therapies (e.g., treatment of an anticancer agent, chemotherapy agent, or neurodegenerative disease). The compounds disclosed herein can be administered alone or co-administered to a patient. Co-administration means the simultaneous or sequential administration of compounds (more than one compound or agent) alone or in combination. Therefore, formulations can also be combined with other active substances when needed (e.g., to reduce metabolic degradation). The compositions of this disclosure can be delivered perdermally via a local route and formulated as application sticks, solutions, suspensions, emulsions, gels, creams, ointments, pastes, gels, paints, powders, and aerosols. Oral formulations include tablets, pills, powders, lozenges, capsules, liquids, tablets, capsules, gels, syrups, slurries, suspensions, etc., suitable for patient ingestion. Solid form formulations include powders, tablets, pills, capsules, capsules, suppositories, and dispersible granules. Liquid form formulations include solutions, suspensions, and emulsions, such as water or water / propylene glycol solutions. The compositions of this disclosure may additionally include components that provide sustained release and / or comfort. Such components include high molecular weight, anionic mucin-mimicking polymers, gelling polysaccharides, and finely fragmented drug carrier matrices. These components are discussed in more detail in U.S. Patent 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 for all purposes. The compositions disclosed herein can also be delivered as microspheres for slow release in vivo. For example, microspheres can be administered via intradermal injection of drug-containing microspheres that release slowly subcutaneously (see Rao, J. Biomater Sci. Polym. Ed . 7:623-645, 1995); as a biodegradable and injectable gel formulation (see, e.g., Gao Pharm. Res . 12:857-863, 1995); or as microspheres for oral administration (see, for example, Eyles, J. Pharm. Pharmacol.49:669-674, 1997). In another embodiment, formulations of the compositions of this disclosure can be delivered using liposomes, which fuse with or endocytose cell membranes, for example by using receptor ligands attached to the liposomes, the ligands binding to cell surface membrane protein receptors, resulting in endocytosis. By using liposomes, particularly when the liposome surface carries receptor ligands specific to target cells, or otherwise preferentially targeting specific organs, the delivery of the compositions of this disclosure can be concentrated in target cells in vivo. (See, for example, 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 disclosed herein can also be used for nanoparticle delivery.

[0099] "Co-administration" means that the compositions described herein are administered simultaneously with, before, or immediately after one or more other therapies. The compounds disclosed herein can be administered alone or co-administered to a patient. Co-administration means administering compounds (more than one compound) simultaneously or sequentially, alone or in combination. The compositions disclosed herein can be delivered transdermally, topically, or formulated as application sticks, solutions, suspensions, emulsions, gels, creams, ointments, pastes, jelly agents, paints, powders, and aerosols.

[0100] Using the teachings provided herein, effective preventative or therapeutic treatment regimens can be planned that do not cause substantial toxicity and are also effective in treating clinical symptoms presented by a particular patient. Such planning should involve careful selection of the active compound by considering factors such as compound potency, relative bioavailability, patient weight, the presence and severity of adverse side effects, administration method, and the toxicological characteristics of the chosen agent.

[0101] The compounds described herein may be used in combination with other active agents known to be used to treat mental or psychiatric disorders, mood disorders, neurological conditions or disorders, metabolic disorders (e.g., type 2 diabetes and / or its complications), endometriosis, glaucoma, pain, Parkinson's disease, migraine, viral infections, bacterial infections, fungal infections, autoimmune diseases, lymphoma, pancreatitis, opioid overdose, influenza infection, or inflammatory disorders.

[0102] 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 the second active agent. Co-administration includes administering the two active agents simultaneously, approximately simultaneously (e.g., within about 1, 5, 10, 15, 20, or 30 minutes of each other), or sequentially in any order. In some embodiments, co-administration can be achieved through co-formulation, such as preparing a single pharmaceutical composition comprising the two active agents. In other embodiments, the active agents can be formulated individually. In another embodiment, the active agents and / or adjuvants can be linked or conjugated to each other. In some embodiments, the compounds described herein can be combined with treatments for infection (e.g., bacterial infection), inflammation, and / or vasodilation.

[0103] The compounds described herein can be administered to treat metabolic diseases or conditions (e.g., type 2 diabetes and / or its complications), mental or psychiatric disorders, mood disorders, neurological disorders or disturbances, endometriosis, glaucoma, pain, Parkinson's disease, migraine, viral infections, bacterial infections, fungal infections, autoimmune diseases, lymphoma, pancreatitis, opioid overdose, influenza infection, or inflammatory disorders. In this regard, the compounds disclosed herein can be administered alone to treat such diseases or disorders, or can be administered in combination with another therapeutic agent to treat such diseases or disorders.

[0104] The compounds disclosed herein can be used in combination with other active agents, including but not limited to antidepressants, antipsychotics, anti-inflammatory drugs, anxiolytics, and / or analgesics.

[0105] The APIs disclosed in this article (e.g., rotigotine, eletriptan, copanlixetine, remdesivir, naphamostat (naphamostat mesylate), levodopa, tigecycline, naloxone, amikacin, 1-amantadine, 2-amantadine, rimantadine, midazolam, amipridine, caspofungin, rapamycin, clonidine, ketamine, methoxetamine, dechlorinated ketamine, tryptamine, phenethylamine, ergotamine compounds, opioids, cathinone compounds, 3,4-methylenedioxyamphetamine derivatives, aminoalkyl-substituted benzofurans, substituted amphetamines, aminoindane, stimulants, diphenhydramine, hydrooxazine, phenylephrine, dopamine, epinephrine, lidocaine, oxymetazoline, chlormastine, chlorpheniramine, or 6-chloro-2-aminonaphthol, etc.) may be administered once daily until the study endpoint is reached. The inhibitors disclosed in this article can be administered at least three times, but in some studies they have been administered four or more times, depending on the length of the study and / or the design of the study.

[0106] As used herein, the term "bioavailability (F)" refers to the portion of a drug dose (e.g., adrenaline) absorbed from its site of administration and reaching the systemic circulation in its unaltered form. The term "absolute bioavailability" refers to the proportion of a drug absorbed in relation to its intravenous bioavailability. It can be calculated using the following formula: The term relative bioavailability (F) rel This is used to compare two different extravascular drug administration routes and can be calculated using the following formula: As used in this article, "clearance (CL)" refers to the plasma volume in which the drug is completely cleared per unit time, calculated by dividing the rate of drug clearance by its plasma concentration. CL is equal to the elimination rate constant (λ) multiplied by the distribution volume (V). d ), where "V" d "AUC" refers to the fluid volume required to contain the amount of drug present in the body at the same concentration as in plasma. The term "apparent clearance (CL / F)" as used herein refers to clearance without regard to drug bioavailability. It is the ratio of dose to AUC.

[0107] "Control" or "controlled experiment" is used in its general sense and refers to an experiment in which the subjects or reagents are treated as in a parallel experiment, except that the experimental procedures, reagents, or variables are omitted. In some instances, a control is used as a comparative standard for evaluating the effectiveness of an experiment. In some embodiments, a control is a measurement of protein activity in the absence of the compounds described herein (including embodiments and examples).

[0108] Typically, the dosage level of a pharmaceutical compound (API) in a composition can be in the range of about 5 μg / kg to about 10 mg / kg, about 0.5 mg / kg to about 5 mg / kg, about 1 mg / kg to about 3 mg / kg, or a fixed dose of about 10-100 mg, or 20-75 mg, or 3-60 mg, or 10-250 mg, or 10-400 mg, or greater than 400 mg.

[0109] "Substantially pure" means that the component constitutes more than about 50% of the total content of the composition, typically more than about 60%. More typically, "substantially pure" means a composition 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 peptide will constitute more than about 90% or more than about 95% of the total content of the composition (by weight).

[0110] It should be noted that throughout the application, alternatives are written in the Markush group, for example, at each amino acid position containing more than one possible amino acid. It is specifically expected that each member of the Markush group should be considered individually, thus including another embodiment, and the Markush group should not be interpreted as a single unit.

[0111] "Contact" is used in its ordinary sense and refers to a process that allows at least two different species (e.g., chemical compounds including biomolecules or cells) to come close enough to react, interact, or physically contact. It should be understood that, however, the resulting reaction product may be produced directly from the reaction between the added reagents, or from an intermediate of one or more added reagents that may be produced in the reaction mixture.

[0112] The term "contact" can include causing two substances to react, interact, or physically come into contact, wherein the two substances may be the compounds and proteins or enzymes described herein. In some embodiments, contact includes causing the compounds described herein to interact with proteins or enzymes involved in signal transduction pathways, such as the MAP kinase pathway.

[0113] As defined in this article, the term "activation," "activate," or "activating" in relation to proteins refers to the transformation of a protein from an initially inactive or inactivated state into a biologically active derivative. The terms "activation," "sensitization," or "upregulation" refer to the reduction in protein activity during signal transduction or enzyme activity, or in diseases.

[0114] The terms "agonist," "activator," "upregulator," etc., refer to substances that can detectably increase the expression or activity of a given gene or protein. Compared to a control without an agonist, an agonist can increase expression or activity by 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or more. In some cases, the expression or activity is 1.5, 2, 3, 4, 5, 10, or higher than that without an agonist. In embodiments, an agonist is a molecule that interacts with a target to cause or promote an increase in target activation. In embodiments, an activator is a molecule that increases, activates, promotes, enhances activation, sensitizes, or upregulates, for example, a gene, protein, ligand, receptor, or cell.

[0115] The "activity" of a molecule can describe or refer to the binding of a molecule to a ligand or receptor; catalytic activity; the ability to stimulate gene expression or cell signaling, differentiation or maturation; the activity of antigens; the regulation of the activity of other molecules; and so on.

[0116] The term “weight osmolality” as used herein is defined as the number of osmol of solute per kilogram of solvent (Osm) (osmol / kg or Osm / kg).

[0117] The term “osmolality” as used herein is defined as the number of osmol / L or Osm / L of solute per liter (L) of solution.

[0118] The isotonic concentration molar ratio can be calculated from the weight osmolality as follows: Isotonic concentration molar ratio = weight osmolality × (ρ sol -c a ); where ρ sol is the density of the solution in g / mL and ca is the concentration of the (anhydrous) solute in g / mL. Unless otherwise explicitly stated, isotonic molar concentration is calculated using the aforementioned formula. Alternatively, isotonic molar concentration can be calculated experimentally.

[0119] Composition Complexing salts of drug compounds This document provides salts of a pharmaceutical compound comprising at least one basic nitrogen in the form of its conjugate acid and a complexing agent in the form of its conjugate base. Such salts are advantageous over other salts of the compound because they are more soluble than many other salt forms due to the properties of the complexing agent and its ability to dissolve the compound. Furthermore, in some embodiments, the preparation of such a complexing agent / pharmaceutical compound salt yields a composition that, upon dissolution or otherwise, will have a lower osmotic molar concentration than a combination of individual salts of each component or a combination of individual salts of each component.

[0120] In one aspect, this document provides pharmaceutically acceptable salts of compound drugs, comprising: (i) a drug compound or an enantiomer, mixture of enantiomers, or isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the drug compound contains a protonated nitrogen atom and 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 of the plurality of acidic functional groups acts as a counter ion of the drug compound, wherein the ratio of the conjugate base of the complexing agent to the drug compound in the pharmaceutically acceptable salt is from about 1:1 to about 1:4. In some embodiments, the pKa of the drug compound is from about 1 to about 7. In some embodiments, the pKa of the drug compound is from about 1 to about 5. In some embodiments, the pKa of the drug compound is from about 5 to about 7. In some embodiments, the conjugate base interacts with a monovalent cation. In some embodiments, the monovalent cation includes Na. + K + H + Li +Or a combination of two or more thereof. In some embodiments, the pharmaceutical compound is an antiviral compound, an antibacterial compound, an antifungal compound, a compound for treating neurological disorders, a compound for treating Parkinson's disease, a treatment for migraines, a treatment for autoimmune diseases, a treatment for cancer, a treatment for lymphoma, a treatment for pancreatitis, a treatment for opioid overdose, a treatment for influenza infection, or a treatment for inflammatory disorders. In some embodiments, the pharmaceutical compound includes rotigotine, eletriptan, DXM, copanlixine, remdesivir, nafamostat (nafamostat mesylate), levodopa, tigecycline, naloxone, amikacin, 1-amantadine, 2-amantadine, rimantadine, amipridine, rapamycin, clonidine, or caspofungin. In some embodiments, the solubility of the pharmaceutical compound is below a threshold. In some embodiments, the solubility of the pharmaceutical compound is above a threshold. In some embodiments, the pKa of the pharmaceutical compound is above a threshold. In some embodiments, the pKa of the pharmaceutical compound is below a threshold.

[0121] In some embodiments, the drug compound has a solubility greater than 100 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 90 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 80 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 70 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 60 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 50 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 45 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 40 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 35 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 30 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 25 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 20 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 10 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 9 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 8 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 7 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 6 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 5 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 4 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 3 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 2 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 1 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.9 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.8 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.7 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.6 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.5 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.4 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.3 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.2 mg / ml as a salt.In some embodiments, the drug compound has a solubility greater than 0.1 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.09 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.08 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.07 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.06 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.05 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.04 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.03 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.02 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.01 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.009 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.008 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.007 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.006 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.005 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.004 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.003 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.002 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.001 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.9 µg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.8 µg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.7 µg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.6 µg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.5 µg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.4 µg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.3 µg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.2 µg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.1 µg / ml as a salt.In some embodiments, the solubility of the drug compound as a salt is greater than 0.09 µg / ml. In some embodiments, the solubility of the drug compound as a salt is greater than 0.08 µg / ml. In some embodiments, the solubility of the drug compound as a salt is greater than 0.07 µg / ml. In some embodiments, the solubility of the drug compound as a salt is greater than 0.06 µg / ml. In some embodiments, the solubility of the drug compound as a salt is greater than 0.05 µg / ml. In some embodiments, the solubility of the drug compound as a salt is greater than 0.04 µg / ml. In some embodiments, the solubility of the drug compound as a salt is greater than 0.03 µg / ml. In some embodiments, the solubility of the drug compound as a salt is greater than 0.02 µg / ml. In some embodiments, the solubility of the drug compound as a salt is greater than 0.01 µg / ml. In some embodiments, the solubility of the drug compound as a salt is greater than 0.009 µg / ml. In some embodiments, the solubility of the drug compound as a salt is greater than 0.008 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is greater than 0.007 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is greater than 0.006 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is greater than 0.005 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is greater than 0.004 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is greater than 0.003 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is greater than 0.002 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is greater than 0.001 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is measured in an aqueous medium. In some embodiments, the solubility of the pharmaceutical compound as a salt is measured in an organic solvent. In some embodiments, the aqueous medium includes water. In some embodiments, the salt of the pharmaceutical compound includes an HCl salt.

[0122] In some embodiments, the solubility of the drug compound as a salt is between about 0.001 mg / ml and 100 mg / ml. In some embodiments, the solubility of the drug compound as a salt is between about 0.01 mg / ml and 50 mg / ml. In some embodiments, the solubility of the drug compound as a salt is between about 0.02 mg / ml and 40 mg / ml. In some embodiments, the solubility of the drug compound as a salt is between about 0.03 mg / ml and 30 mg / ml. In some embodiments, the solubility of the drug compound as a salt is between about 0.04 mg / ml and 20 mg / ml. In some embodiments, the solubility of the drug compound as a salt is between about 0.05 mg / ml and 10 mg / ml. In some embodiments, the solubility of the drug compound as a salt is between about 0.06 mg / ml and 5 mg / ml. In some embodiments, the solubility of the drug compound as a salt is between about 0.07 mg / ml and 4 mg / ml. In some embodiments, the solubility of the drug compound as a salt is between about 0.09 mg / ml and 3 mg / ml. In some embodiments, the solubility of the drug compound as a salt is between about 0.1 mg / ml and 2 mg / ml. In some embodiments, the solubility of the drug compound as a salt is measured in an aqueous medium. In some embodiments, the solubility of the drug compound as a salt is measured in an organic solvent. In some embodiments, the aqueous medium includes water. In some embodiments, the salt of the drug compound includes an HCl salt.

[0123] In some embodiments, the solubility of the drug compound as a salt is less than 100 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 90 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 80 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 70 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 60 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 50 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 45 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 40 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 35 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 30 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 25 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 20 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 10 mg / ml. In some embodiments, the drug compound has a solubility of less than 9 mg / ml as a salt. In some embodiments, the drug compound has a solubility of less than 8 mg / ml as a salt. In some embodiments, the drug compound has a solubility of less than 7 mg / ml as a salt. In some embodiments, the drug compound has a solubility of less than 6 mg / ml as a salt. In some embodiments, the drug compound has a solubility of less than 5 mg / ml as a salt. In some embodiments, the drug compound has a solubility of less than 4 mg / ml as a salt. In some embodiments, the drug compound has a solubility of less than 3 mg / ml as a salt. In some embodiments, the drug compound has a solubility of greater than 2 mg / ml as a salt. In some embodiments, the drug compound has a solubility of less than 1 mg / ml as a salt. In some embodiments, the drug compound has a solubility of less than 0.9 mg / ml as a salt. In some embodiments, the drug compound has a solubility of less than 0.8 mg / ml as a salt. In some embodiments, the drug compound has a solubility of less than 0.7 mg / ml as a salt. In some embodiments, the drug compound has a solubility of less than 0.6 mg / ml as a salt. In some embodiments, the solubility of the drug compound as a salt is less than 0.5 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.4 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.3 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.2 mg / ml.In some embodiments, the solubility of the drug compound as a salt is less than 0.1 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.09 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.08 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.07 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.06 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.05 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.04 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.03 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.02 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.01 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.009 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.008 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.007 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.006 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.005 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.004 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.003 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.002 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.001 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.9 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.8 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.7 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.6 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.5 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.4 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.3 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.2 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.1 µg / ml.In some embodiments, the solubility of the drug compound as a salt is less than 0.09 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.08 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.07 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.06 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.05 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.04 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.03 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.02 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.01 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.009 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.008 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is less than 0.007 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is less than 0.006 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is less than 0.005 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is less than 0.004 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is less than 0.003 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is less than 0.002 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is less than 0.001 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is measured in an aqueous medium. In some embodiments, the solubility of the pharmaceutical compound as a salt is measured in an organic solvent. In some embodiments, the aqueous medium includes water. In some embodiments, the salt of the pharmaceutical compound includes an HCl salt.

[0124] In some embodiments, the drug compound has a solubility greater than 100 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 90 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 80 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 70 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 60 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 50 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 45 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 40 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 35 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 30 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 25 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 20 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 10 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 9 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 8 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 7 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 6 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 5 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 4 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 3 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 2 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 1 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.9 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.8 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.7 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.6 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.5 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.4 mg / ml as a free base.In some embodiments, the drug compound has a solubility greater than 0.3 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.2 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.1 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.09 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.08 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.07 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.06 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.05 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.04 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.03 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.02 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.01 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.009 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.008 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.007 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.006 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.005 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.004 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.003 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.002 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.001 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.9 µg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.8 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.7 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.6 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.5 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.4 µg / ml.In some embodiments, the drug compound has a solubility greater than 0.3 µg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.2 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.1 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.09 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.08 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.07 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.06 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.05 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.04 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.03 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.02 µg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.01 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.009 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.008 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.007 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.006 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.005 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.004 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.003 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.002 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a free base is greater than 0.001 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a free base is measured in an aqueous medium. In some embodiments, the solubility of the pharmaceutical compound as a free base is measured in an organic solvent. In some embodiments, the aqueous medium includes water.

[0125] In some embodiments, the solubility of the drug compound as a free base is between about 0.001 mg / ml and 100 mg / ml. In some embodiments, the solubility of the drug compound as a free base is between about 0.01 mg / ml and 50 mg / ml. In some embodiments, the solubility of the drug compound as a free base is between about 0.02 mg / ml and 40 mg / ml. In some embodiments, the solubility of the drug compound as a free base is between about 0.03 mg / ml and 30 mg / ml. In some embodiments, the solubility of the drug compound as a free base is between about 0.04 mg / ml and 20 mg / ml. In some embodiments, the solubility of the drug compound as a free base is between about 0.05 mg / ml and 10 mg / ml. In some embodiments, the solubility of the drug compound as a free base is between about 0.06 mg / ml and 5 mg / ml. In some embodiments, the solubility of the drug compound as a free base is between about 0.07 mg / ml and 4 mg / ml. In some embodiments, the solubility of the pharmaceutical compound as a free base is between about 0.09 mg / ml and 3 mg / ml. In some embodiments, the solubility of the pharmaceutical compound as a free base is between about 0.1 mg / ml and 2 mg / ml. In some embodiments, the solubility of the pharmaceutical compound as a free base is measured in an aqueous medium. In some embodiments, the solubility of the pharmaceutical compound as a free base is measured in an organic solvent. In some embodiments, the aqueous medium includes water.

[0126] In some embodiments, the solubility of the drug compound as a free base is less than 100 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 90 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 80 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 70 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 60 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 50 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 45 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 40 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 35 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 30 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 25 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 20 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 10 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 9 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 8 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 7 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 6 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 5 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 4 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 3 mg / ml. In some embodiments, the solubility of the drug compound as a free base is greater than 2 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 1 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.9 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.8 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.7 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.6 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.5 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.4 mg / ml.In some embodiments, the solubility of the drug compound as a free base is less than 0.3 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.2 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.1 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.09 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.08 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.07 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.06 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.05 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.04 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.03 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.02 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.01 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.009 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.008 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.007 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.006 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.005 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.004 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.003 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.002 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.001 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.9 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.8 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.7 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.6 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.5 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.4 µg / ml.In some embodiments, the solubility of the drug compound as a free base is less than 0.3 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.2 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.1 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.09 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.08 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.07 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.06 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.05 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.04 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.03 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.02 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.01 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.009 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.008 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.007 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.006 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.005 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.004 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.003 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.002 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a free base is less than 0.001 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a free base is measured in an aqueous medium. In some embodiments, the solubility of the pharmaceutical compound as a free base is measured in an organic solvent. In some embodiments, the aqueous medium includes water.

[0127] In some embodiments, the ratio of the conjugate base of the chelating agent in a pharmaceutically acceptable salt to the drug compound is from about 1:1 to about 1:4. In some embodiments, the ratio is from about 1:1.1 to about 1:3.9. In some embodiments, the ratio is from about 1:1.2 to about 1:3.8. In some embodiments, the ratio is from about 1:1.3 to about 1:3.7. In some embodiments, the ratio is from about 1:1.4 to about 1:3.6. In some embodiments, the ratio is from about 1:1.5 to about 1:3.5. In some embodiments, the ratio of the conjugate base of the chelating agent in a pharmaceutically acceptable salt to the drug compound is from about 1:1.6 to about 1:3.4. In some embodiments, the ratio is from about 1:1.7 to about 1:3.3. In some embodiments, the ratio is from about 1:1.8 to about 1:3.2. In some embodiments, the ratio is from about 1:1.9 to about 1:3.1. In some embodiments, the ratio is from about 1:2 to about 1:3. In some embodiments, the ratio is from about 1:2.1 to about 1:2.9. In some embodiments, the ratio of the conjugate base of the chelating agent to the drug compound in a 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 chelating agent to the drug compound in a 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 chelating agent to the drug compound in a 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 in a pharmaceutically acceptable salt to the pharmaceutical compound is 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 between these ratios.

[0128] In some embodiments, the complexing agent acts as a counterion between 1 to 4 drug compound molecules in a pharmaceutically acceptable salt. In some embodiments, the complexing agent further includes a nonpolar region. In some embodiments, the pharmaceutically acceptable salt contains an additional molar equivalent of the unionized form of the drug compound compared to the amount of the complexing agent. In some embodiments, the additional molar equivalent of the unionized form of the drug compound complexes with the complexing agent via the nonpolar region.

[0129] In some embodiments, the solubility of the drug compound in a pharmaceutically acceptable salt is higher than (i) the solubility of the drug compound as a salt; or (ii) the solubility of the drug compound complexed with a nonpolar pore of a complexing agent in a salt containing the drug compound in its free base form, wherein the drug compound has the same concentration in the pharmaceutically acceptable salt, the drug compound as a salt, and the salt containing the drug compound in its free base form. In some embodiments, the solubility of the drug compound in a pharmaceutically acceptable salt is higher than the solubility of the drug compound in a salt containing a drug compound with a higher molar ratio to a complexing agent and the drug compound in a complexing agent, wherein the drug compound has the same concentration in both the pharmaceutically acceptable salt and the salt containing the drug compound with a higher molar ratio to a complexing agent. In some embodiments, the solubility of the drug compound in a pharmaceutically acceptable salt is increased by at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, or 100 times compared to (i) the solubility of the drug compound as a salt; or (ii) the solubility of the drug compound in a salt containing the drug compound in the form of a free base, wherein the drug compound has the same concentration in the pharmaceutically acceptable salt, the drug compound as a salt, and the salt containing the drug compound in the form of a free base. In some embodiments, the solubility of the drug compound in a pharmaceutically acceptable salt is increased by at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, or 100 times compared to the solubility of the drug compound in a salt containing a high molar ratio of the drug compound to the complexing agent, wherein the drug compound has the same concentration in both the pharmaceutically acceptable salt and the salt containing a high molar ratio of the drug compound to the complexing agent.

[0130] In one aspect, this document provides a pharmaceutically acceptable salt of a compound drug comprising: (i) a drug compound or an enantiomer, mixture of enantiomers, or isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the drug compound contains a protonated nitrogen atom and 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 acting as an anti-ion of the protonated nitrogen atom of the drug compound, wherein the ratio of the conjugate base of the complexing agent to the drug compound in the pharmaceutically acceptable salt is from about 1:1 to about 1:4; and an additional molar equivalent of the drug compound, wherein the additional molar equivalent of the drug compound is unionized. In some embodiments, the pKa of the drug compound is from about 1 to about 7, from about 1 to about 6, from about 1 to about 5, from about 1 to about 4, from about 1 to about 3, or from about 1 to about 2. In some embodiments, the pKa of the drug compound is from about 1 to about 5. In some embodiments, the pKa of the drug compound is from about 4 to about 7. In some embodiments, the complexing agent acts as a counterion between 1 to 4 drug compound molecules in a pharmaceutically acceptable salt. In some embodiments, the solubility of the drug compound is below a threshold. In some embodiments, the solubility of the drug compound is above a threshold. In some embodiments, the pKa of the drug compound is above a threshold. In some embodiments, the pKa of the drug compound is below a threshold.

[0131] In some embodiments, the chelating agent further includes a nonpolar region. In some embodiments, an additional molar equivalent of the unionized form of the pharmaceutical compound is complexed with the chelating agent via the nonpolar region. In some embodiments, the pharmaceutical compound is an antiviral compound, an antibacterial compound, an antifungal compound, a compound for treating neurological disorders, a compound for treating Parkinson's disease, a treatment for migraines, a treatment for autoimmune diseases, a treatment for cancer, a treatment for lymphoma, a treatment for pancreatitis, a treatment for opioid overdose, a treatment for influenza infection, or a treatment for inflammatory disorders. In some embodiments, the pharmaceutical compound includes rotigotine, eletriptan, copanlixin, remdesivir, nafamostat (nafamostat mesylate), levodopa, tigecycline, naloxone, amikacin, 1-amantadine, 2-amantadine, rimantadine, amipridine, rapamycin, clonidine, or caspofungin. In some embodiments, the chelating agent is sulfobutyl ether-β-cyclodextrin.

[0132] In some embodiments, the drug compound has a solubility greater than 100 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 90 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 80 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 70 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 60 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 50 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 45 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 40 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 35 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 30 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 25 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 20 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 10 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 9 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 8 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 7 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 6 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 5 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 4 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 3 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 2 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 1 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.9 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.8 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.7 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.6 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.5 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.4 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.3 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.2 mg / ml as a salt.In some embodiments, the drug compound has a solubility greater than 0.1 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.09 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.08 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.07 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.06 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.05 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.04 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.03 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.02 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.01 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.009 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.008 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.007 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.006 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.005 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.004 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.003 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.002 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.001 mg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.9 µg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.8 µg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.7 µg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.6 µg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.5 µg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.4 µg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.3 µg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.2 µg / ml as a salt. In some embodiments, the drug compound has a solubility greater than 0.1 µg / ml as a salt.In some embodiments, the solubility of the drug compound as a salt is greater than 0.09 µg / ml. In some embodiments, the solubility of the drug compound as a salt is greater than 0.08 µg / ml. In some embodiments, the solubility of the drug compound as a salt is greater than 0.07 µg / ml. In some embodiments, the solubility of the drug compound as a salt is greater than 0.06 µg / ml. In some embodiments, the solubility of the drug compound as a salt is greater than 0.05 µg / ml. In some embodiments, the solubility of the drug compound as a salt is greater than 0.04 µg / ml. In some embodiments, the solubility of the drug compound as a salt is greater than 0.03 µg / ml. In some embodiments, the solubility of the drug compound as a salt is greater than 0.02 µg / ml. In some embodiments, the solubility of the drug compound as a salt is greater than 0.01 µg / ml. In some embodiments, the solubility of the drug compound as a salt is greater than 0.009 µg / ml. In some embodiments, the solubility of the drug compound as a salt is greater than 0.008 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is greater than 0.007 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is greater than 0.006 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is greater than 0.005 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is greater than 0.004 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is greater than 0.003 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is greater than 0.002 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is greater than 0.001 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is measured in an aqueous medium. In some embodiments, the solubility of the pharmaceutical compound as a salt is measured in an organic solvent. In some embodiments, the aqueous medium includes water. In some embodiments, the salt of the pharmaceutical compound includes an HCl salt.

[0133] In some embodiments, the solubility of the drug compound as a salt is between about 0.001 mg / ml and 100 mg / ml. In some embodiments, the solubility of the drug compound as a salt is between about 0.01 mg / ml and 50 mg / ml. In some embodiments, the solubility of the drug compound as a salt is between about 0.02 mg / ml and 40 mg / ml. In some embodiments, the solubility of the drug compound as a salt is between about 0.03 mg / ml and 30 mg / ml. In some embodiments, the solubility of the drug compound as a salt is between about 0.04 mg / ml and 20 mg / ml. In some embodiments, the solubility of the drug compound as a salt is between about 0.05 mg / ml and 10 mg / ml. In some embodiments, the solubility of the drug compound as a salt is between about 0.06 mg / ml and 5 mg / ml. In some embodiments, the solubility of the drug compound as a salt is between about 0.07 mg / ml and 4 mg / ml. In some embodiments, the solubility of the drug compound as a salt is between about 0.09 mg / ml and 3 mg / ml. In some embodiments, the solubility of the drug compound as a salt is between about 0.1 mg / ml and 2 mg / ml. In some embodiments, the solubility of the drug compound as a salt is measured in an aqueous medium. In some embodiments, the solubility of the drug compound as a salt is measured in an organic solvent. In some embodiments, the aqueous medium includes water. In some embodiments, the salt of the drug compound includes an HCl salt.

[0134] In some embodiments, the solubility of the drug compound as a salt is less than 100 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 90 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 80 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 70 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 60 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 50 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 45 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 40 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 35 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 30 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 25 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 20 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 10 mg / ml. In some embodiments, the drug compound has a solubility of less than 9 mg / ml as a salt. In some embodiments, the drug compound has a solubility of less than 8 mg / ml as a salt. In some embodiments, the drug compound has a solubility of less than 7 mg / ml as a salt. In some embodiments, the drug compound has a solubility of less than 6 mg / ml as a salt. In some embodiments, the drug compound has a solubility of less than 5 mg / ml as a salt. In some embodiments, the drug compound has a solubility of less than 4 mg / ml as a salt. In some embodiments, the drug compound has a solubility of less than 3 mg / ml as a salt. In some embodiments, the drug compound has a solubility of greater than 2 mg / ml as a salt. In some embodiments, the drug compound has a solubility of less than 1 mg / ml as a salt. In some embodiments, the drug compound has a solubility of less than 0.9 mg / ml as a salt. In some embodiments, the drug compound has a solubility of less than 0.8 mg / ml as a salt. In some embodiments, the drug compound has a solubility of less than 0.7 mg / ml as a salt. In some embodiments, the drug compound has a solubility of less than 0.6 mg / ml as a salt. In some embodiments, the solubility of the drug compound as a salt is less than 0.5 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.4 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.3 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.2 mg / ml.In some embodiments, the solubility of the drug compound as a salt is less than 0.1 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.09 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.08 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.07 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.06 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.05 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.04 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.03 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.02 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.01 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.009 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.008 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.007 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.006 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.005 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.004 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.003 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.002 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.001 mg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.9 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.8 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.7 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.6 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.5 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.4 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.3 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.2 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.1 µg / ml.In some embodiments, the solubility of the drug compound as a salt is less than 0.09 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.08 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.07 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.06 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.05 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.04 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.03 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.02 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.01 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.009 µg / ml. In some embodiments, the solubility of the drug compound as a salt is less than 0.008 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is less than 0.007 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is less than 0.006 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is less than 0.005 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is less than 0.004 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is less than 0.003 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is less than 0.002 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is less than 0.001 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a salt is measured in an aqueous medium. In some embodiments, the solubility of the pharmaceutical compound as a salt is measured in an organic solvent. In some embodiments, the aqueous medium includes water. In some embodiments, the salt of the pharmaceutical compound includes an HCl salt.

[0135] In some embodiments, the drug compound has a solubility greater than 100 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 90 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 80 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 70 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 60 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 50 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 45 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 40 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 35 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 30 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 25 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 20 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 10 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 9 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 8 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 7 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 6 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 5 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 4 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 3 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 2 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 1 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.9 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.8 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.7 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.6 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.5 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.4 mg / ml as a free base.In some embodiments, the drug compound has a solubility greater than 0.3 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.2 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.1 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.09 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.08 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.07 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.06 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.05 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.04 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.03 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.02 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.01 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.009 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.008 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.007 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.006 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.005 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.004 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.003 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.002 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.001 mg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.9 µg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.8 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.7 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.6 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.5 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.4 µg / ml.In some embodiments, the drug compound has a solubility greater than 0.3 µg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.2 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.1 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.09 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.08 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.07 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.06 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.05 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.04 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.03 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.02 µg / ml as a free base. In some embodiments, the drug compound has a solubility greater than 0.01 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.009 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.008 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.007 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.006 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.005 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.004 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.003 µg / ml. In some embodiments, the drug compound has a solubility greater than 0.002 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a free base is greater than 0.001 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a free base is measured in an aqueous medium. In some embodiments, the solubility of the pharmaceutical compound as a free base is measured in an organic solvent. In some embodiments, the aqueous medium includes water.

[0136] In some embodiments, the solubility of the drug compound as a free base is between about 0.001 mg / ml and 100 mg / ml. In some embodiments, the solubility of the drug compound as a free base is between about 0.01 mg / ml and 50 mg / ml. In some embodiments, the solubility of the drug compound as a free base is between about 0.02 mg / ml and 40 mg / ml. In some embodiments, the solubility of the drug compound as a free base is between about 0.03 mg / ml and 30 mg / ml. In some embodiments, the solubility of the drug compound as a free base is between about 0.04 mg / ml and 20 mg / ml. In some embodiments, the solubility of the drug compound as a free base is between about 0.05 mg / ml and 10 mg / ml. In some embodiments, the solubility of the drug compound as a free base is between about 0.06 mg / ml and 5 mg / ml. In some embodiments, the solubility of the drug compound as a free base is between about 0.07 mg / ml and 4 mg / ml. In some embodiments, the solubility of the pharmaceutical compound as a free base is between about 0.09 mg / ml and 3 mg / ml. In some embodiments, the solubility of the pharmaceutical compound as a free base is between about 0.1 mg / ml and 2 mg / ml. In some embodiments, the solubility of the pharmaceutical compound as a free base is measured in an aqueous medium. In some embodiments, the solubility of the pharmaceutical compound as a free base is measured in an organic solvent. In some embodiments, the aqueous medium includes water.

[0137] In some embodiments, the solubility of the drug compound as a free base is less than 100 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 90 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 80 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 70 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 60 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 50 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 45 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 40 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 35 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 30 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 25 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 20 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 10 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 9 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 8 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 7 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 6 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 5 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 4 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 3 mg / ml. In some embodiments, the solubility of the drug compound as a free base is greater than 2 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 1 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.9 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.8 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.7 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.6 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.5 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.4 mg / ml.In some embodiments, the solubility of the drug compound as a free base is less than 0.3 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.2 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.1 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.09 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.08 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.07 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.06 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.05 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.04 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.03 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.02 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.01 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.009 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.008 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.007 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.006 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.005 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.004 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.003 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.002 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.001 mg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.9 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.8 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.7 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.6 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.5 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.4 µg / ml.In some embodiments, the solubility of the drug compound as a free base is less than 0.3 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.2 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.1 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.09 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.08 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.07 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.06 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.05 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.04 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.03 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.02 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.01 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.009 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.008 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.007 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.006 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.005 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.004 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.003 µg / ml. In some embodiments, the solubility of the drug compound as a free base is less than 0.002 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a free base is less than 0.001 µg / ml. In some embodiments, the solubility of the pharmaceutical compound as a free base is measured in an aqueous medium. In some embodiments, the solubility of the pharmaceutical compound as a free base is measured in an organic solvent. In some embodiments, the aqueous medium includes water.

[0138] In some embodiments, the ratio of the conjugate base of the chelating agent in a pharmaceutically acceptable salt to the drug compound is from about 1:1 to about 1:4. In some embodiments, the ratio is from about 1:1.1 to about 1:3.9. In some embodiments, the ratio is from about 1:1.2 to about 1:3.8. In some embodiments, the ratio is from about 1:1.3 to about 1:3.7. In some embodiments, the ratio is from about 1:1.4 to about 1:3.6. In some embodiments, the ratio is from about 1:1.5 to about 1:3.5. In some embodiments, the ratio of the conjugate base of the chelating agent in a pharmaceutically acceptable salt to the drug compound is from about 1:1.6 to about 1:3.4. In some embodiments, the ratio is from about 1:1.7 to about 1:3.3. In some embodiments, the ratio is from about 1:1.8 to about 1:3.2. In some embodiments, the ratio is from about 1:1.9 to about 1:3.1. In some embodiments, the ratio is from about 1:2 to about 1:3. In some embodiments, the ratio is from about 1:2.1 to about 1:2.9. In some embodiments, the ratio of the conjugate base of the chelating agent to the drug compound in a 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 chelating agent to the drug compound in a 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 chelating agent to the drug compound in a 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 in a pharmaceutically acceptable salt to the pharmaceutical compound is 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 between these ratios.

[0139] In some embodiments, the solubility of the drug compound in a pharmaceutically acceptable salt is higher than (i) the solubility of the drug compound as a salt; or (ii) the solubility of the drug compound complexed with a nonpolar pore of a complexing agent in a salt containing the drug compound in its free base form, wherein the drug compound has the same concentration in the pharmaceutically acceptable salt, the drug compound as a salt, and the salt containing the drug compound in its free base form. In some embodiments, the solubility of the drug compound in a pharmaceutically acceptable salt is higher than the solubility of the drug compound in a salt containing a drug compound with a higher molar ratio to a complexing agent and the drug compound in a complexing agent, wherein the drug compound has the same concentration in both the pharmaceutically acceptable salt and the salt containing the drug compound with a higher molar ratio to a complexing agent. In some embodiments, the solubility of the drug compound in a pharmaceutically acceptable salt is increased by at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, or 100 times compared to (i) the solubility of the drug compound as a salt; or (ii) the solubility of the drug compound in a salt containing the drug compound in the form of a free base, wherein the drug compound has the same concentration in the pharmaceutically acceptable salt, the drug compound as a salt, and the salt containing the drug compound in the form of a free base. In some embodiments, the solubility of the drug compound in a pharmaceutically acceptable salt is increased by at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, or 100 times compared to the solubility of the drug compound in a salt containing a high molar ratio of the drug compound to the complexing agent, wherein the drug compound has the same concentration in both the pharmaceutically acceptable salt and the salt containing a high molar ratio of the drug compound to the complexing agent.

[0140] In one aspect, this document provides a pharmaceutically acceptable salt of a compound drug comprising: (i) a drug compound or an enantiomer, mixture of enantiomers, or isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the drug compound comprises a prodrug containing an unionized substance conjugated to a chemical entity, wherein the chemical entity comprises a protonated nitrogen atom and has 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 comprises a conjugate base of an acid that acts as a counterion to the protonated nitrogen atom of the drug 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 the complexing agent. In some embodiments, in a pharmaceutically acceptable salt, the complexing agent acts as a counterion between 1 to 8 drug compound molecules. In some embodiments, the complexing agent further includes a nonpolar region. In some embodiments, about 1 molar equivalent of unionized material complexes with the complexing agent through the nonpolar region. 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 sulfobutyl ether-β-cyclodextrin. In some embodiments, the ratio of the conjugate base of the complexing agent to the drug compound in a pharmaceutically acceptable salt is about 1:4 to about 1:10. In some embodiments, the ratio of the conjugate base of the complexing agent to the drug compound in a pharmaceutically acceptable salt is about 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, or 1:10, or any ratio between these ratios.

[0141] Regarding the prodrug potential of a drug compound or its salt, which has been identified but lacks ionizable nitrogen (e.g., steroid drugs), any natural or synthetic amino acid containing basic or neutral nitrogen can be esterified into a prodrug moiety. In some embodiments, the amino acid may be proline, which has a neutral nitrogen atom that is readily protonated, such as... Figure 4 As shown. Proline provides ionizable nitrogen (pKa of approximately 10.6), which, when protonated, acts as a counter ion to the complexing agent, allowing the protonated prodrug to become a drug compound complexed with the complexing agent. In some embodiments, the complexing agent is SBEBCD.

[0142] In some embodiments, the composition comprises a pharmaceutical compound, including a prodrug pharmaceutical compound. In some embodiments, the prodrug comprises an active pharmaceutical ingredient conjugated to a chemical moiety via an ester bond. In some embodiments, the chemical moiety comprises 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 of two or more thereof.

[0143] In some embodiments, the composition comprises a first pharmaceutical compound or its enantiomers, mixtures of enantiomers, or isotopic variants thereof, including 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 via an ester bond. In some embodiments, the composition comprises a second pharmaceutical compound or its enantiomers, mixtures of enantiomers, or isotopic variants thereof, including 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 via an ester bond. In some embodiments, the first prodrug and the second prodrug are identical. In some embodiments, the first prodrug comprises protonated nitrogen, and the second prodrug does not contain protonated nitrogen. In some embodiments, the first prodrug containing protonated nitrogen is complexed with a complexing agent. In some embodiments, the complexing agent further comprises a nonpolar region. In some embodiments, the nonpolar region is a nonpolar pore. In some embodiments, an additional molar equivalent of unionized material complexes with the nonpolar region of the complexing agent. In some embodiments, an additional molar equivalent of unionized material complexes with the nonpolar pores of the complexing agent.

[0144] In some embodiments, the pharmaceutically acceptable salt comprises 0.1-20 molar equivalents of unionized material compared to the complexing agent. In some embodiments, the pharmaceutically acceptable salt comprises 0.2-15 molar equivalents of unionized material compared to the complexing agent. In some embodiments, the pharmaceutically acceptable salt comprises 0.5-10 molar equivalents of unionized material compared to the complexing agent. In some embodiments, the pharmaceutically acceptable salt comprises 1-5 molar equivalents of unionized material compared to the complexing agent.In some implementations, the pharmaceutically acceptable salt comprises 0.1-20 molar equivalents of unionized substance compared to the complexing agent, for example, 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 0.6, 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 unionized material or any amount in between.In some embodiments, the pharmaceutically acceptable salt comprises 1-2 molar equivalents of unionized material compared to the complexing agent. In some embodiments, 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 unionized material compared to the complexing agent.

[0145] In some embodiments, the molar ratio of cyclodextrin to the pharmaceutical compound containing a protonated nitrogen atom is from about 1:4 to about 1:8. In some embodiments, the molar ratio of cyclodextrin to the pharmaceutical compound containing a protonated nitrogen atom is from about 1:4 to about 1:10. In some embodiments, the molar ratio of cyclodextrin to the pharmaceutical compound containing a protonated nitrogen atom is from about 1:5 to about 1:7. In some embodiments, the molar ratio of cyclodextrin to the pharmaceutical compound containing a protonated nitrogen atom is about 1:4. In some embodiments, the molar ratio of cyclodextrin to the pharmaceutical compound containing a protonated nitrogen atom is about 1:5. In some embodiments, the molar ratio of cyclodextrin to the pharmaceutical compound containing a protonated nitrogen atom is about 1:6. In some embodiments, the molar ratio of cyclodextrin to the pharmaceutical compound containing a protonated nitrogen atom is about 1:7. In some embodiments, the molar ratio of cyclodextrin to the pharmaceutical compound containing a protonated nitrogen atom is about 1:8. In some embodiments, the molar ratio of cyclodextrin to the pharmaceutical compound containing a protonated nitrogen atom is about 1:9. In some embodiments, the molar ratio of cyclodextrin to the pharmaceutical compound containing a protonated nitrogen atom is about 1:10.

[0146] In some embodiments, the molar ratio of the acidic functional group of the chelating agent to the pharmaceutical compound containing a protonated nitrogen atom is from about 2:1 to about 1:2. In some embodiments, the molar ratio of the acidic functional group of the chelating agent to the pharmaceutical compound containing a protonated nitrogen atom is from about 1.75:1 to about 1:1.75. In some embodiments, the molar ratio of the acidic functional group of the chelating agent to the pharmaceutical compound containing a protonated nitrogen atom is from about 1.5:1 to about 1:1.5. In some embodiments, the molar ratio of the acidic functional group of the chelating agent to the pharmaceutical compound containing a protonated nitrogen atom is from about 1.4:1 to about 1:1.4. In some embodiments, the molar ratio of the acidic functional group of the chelating agent to the pharmaceutical compound containing a protonated nitrogen atom is from 1.3:1 to about 1:1.3. In some embodiments, the molar ratio of the acidic functional group of the chelating agent to the pharmaceutical compound containing a protonated nitrogen atom is from about 1.25:1 to about 1:1.25. In some embodiments, the molar ratio of the acidic functional group of the complexing agent to the pharmaceutical compound containing a protonated nitrogen atom is from about 1.2:1 to about 1:1.2. In some embodiments, the molar ratio of the acidic functional group of the complexing agent to the pharmaceutical compound containing a protonated nitrogen atom is from about 1.15:1 to about 1:1.15. In some embodiments, the molar ratio of the acidic functional group of the complexing agent to the pharmaceutical compound containing a protonated nitrogen atom is from about 1.1:1 to about 1:1.1. In some embodiments, the molar ratio of the acidic functional group of the complexing agent to the pharmaceutical compound containing a protonated nitrogen atom is from about 1.05:1 to about 1:1.05. In some embodiments, the molar ratio of the acidic functional group of the complexing agent to the pharmaceutical compound containing a protonated nitrogen atom is about 1:1.

[0147] In some embodiments, the solubility of the unionized substance in a pharmaceutically acceptable salt is higher than (i) the solubility of the unionized substance as a salt; or (ii) the solubility of the unionized substance complexed with a nonpolar pore of a complexing agent in a salt containing the unionized substance in the form of a free base, wherein the unionized substance has the same concentration in the pharmaceutically acceptable salt, the unionized substance as a salt, and the salt containing the unionized substance in the form of a free base. In some embodiments, the solubility of the unionized substance in a pharmaceutically acceptable salt is higher than the solubility of the unionized substance in a salt containing a high molar ratio of unionized substance to complexing agent and the salt containing a complexing agent, wherein the unionized substance has the same concentration in the pharmaceutically acceptable salt and the salt containing a high molar ratio of unionized substance to complexing agent. In some embodiments, the solubility of the unionized substance in a pharmaceutically acceptable salt is increased by at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, or 100 times compared to (i) the solubility of the unionized substance as a salt; or (ii) the solubility of the unionized substance in a salt containing the unionized substance in the form of a free base, which is in the same concentration in the pharmaceutically acceptable salt, the unionized substance as a salt, and the salt containing the unionized substance in the form of a free base. In some embodiments, the solubility of the unionized substance in pharmaceutically acceptable salts is increased by at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, or 100 times compared to the solubility of the unionized substance in salts containing a high molar ratio of unionized substance to complexing agent, wherein the unionized substance has the same concentration in both pharmaceutically acceptable salts and salts containing a high molar ratio of unionized substance to complexing agent.

[0148] In one aspect, this document provides a pharmaceutically acceptable salt of a compound drug comprising: (i) a first drug compound or an enantiomer, mixture of enantiomers, or isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the drug compound comprises a protonated nitrogen atom and the pKa of the drug compound is from about 1 to about 7; (ii) a conjugate base of a complexing agent comprising a plurality of acidic functional groups, wherein at least one of the plurality of acidic functional groups acts as a counter ion of the first drug compound; and (iii) a second drug compound or an enantiomer, mixture of enantiomers, or isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the second drug compound is unionized. In some embodiments, the ratio of the conjugate base of the complexing agent to the first drug compound in the pharmaceutically acceptable salt is from about 1:4 to about 1:10. In some embodiments, the ratio of the conjugate base of the complexing agent in a pharmaceutically acceptable salt to the first drug compound is about 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, or 1:10, or any ratio between these ratios. In some embodiments, the ratio of the conjugate base of the complexing agent in a pharmaceutically acceptable salt to the second drug compound is about 1:1. In some embodiments, the first drug compound comprises an ionized form. In some embodiments, the first drug compound comprises an unionized form. In some embodiments, the second drug compound does not contain ionizable nitrogen atoms. In some embodiments, the pKa value of the second drug compound is above a threshold. In some embodiments, the first drug compound and the second drug compound are the same. In some embodiments, the first drug compound and the second drug compound are different.

[0149] In some embodiments, the chelating agent is sulfobutyl ether-β-cyclodextrin. In some embodiments, the first pharmaceutical compound includes a dissociative pharmaceutical compound, a dissociative hallucinogen compound, a dissociative anesthetic compound, arylcyclohexylamine, 1,2-diarylethylamine, β-keto-arylcyclohexylamine, or a compound that modulates NMDA receptors.In some embodiments, the first pharmaceutical compound is ketamine, arylcyclohexylamine, 1,2-diarylethylamine, β-ketoarylcyclohexylamine, methoxetamine, dechlorinated ketamine, N-ethyl-dechlorinated ketamine (ethoxycyclohexane), 3-methoxyphencyclidine, methoxyethoxycycloidine, ephenidine, lanicillin, dextromethorphan, dextrophenane, methoxyketamine, N,N-dimethyltryptamine, N,N-diethyltryptamine, N,N-dipropyltryptamine, N-methyl-N-propyltryptamine, N-methyl-N-isopropyltryptamine, N,N-diallyltryptamine, N-methyl-N-allyltryptamine, N-methyl-N-ethyltryptamine, N,N- Diisopropyltryptamine, 4-hydroxy-N-methyl-N-ethyltryptamine, 5-methoxy-N,N-diisopropyltryptamine, O-acetylxyloxelosine (psilocin), methyl isopropyl ergotamine, ethyl isopropyl ergotamine, 6-allyl-6-nor-LSD, 6-ethyl-6-nor-lysergic acid diacetamide, 1-acetyl-LSD, 1-propionyl-6-ethyl-6-nor-lysergic acid diacetamide, 1-propionyl-lysergic acid diacetamide, 1-cyclopropionyl-d-lysergic acid diacetamide, N1-butyryl-lysergic acid diacetamide, 6-propyl-6-nor-lysergic acid diacetamide, mescaline, 2,5-dimethoxy 4-Bromophenylethylamine (2C-B), 2-(4-iodo-2,5-dimethoxyphenyl)ethane-1-amine (2C-I), 2-(4-chloro-2,5-dimethoxyphenyl)ethane-1-amine (2C-C), 2,5-dimethoxy-4-iodoamphetamine, 2-[2,5-dimethoxy-4-(propylthio)phenyl]ethane-1-amine, 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethylamine, racemophorone, levonorpheniramine, racemethorphan, buprenorphine, morphine, loperamide, morphine, codeine, hydrocodone, hydroxymorphone, buprenorphine, fentanyl Tannins, methadone, tramadol, α-methylacetylfentanyl, alfentanyl, butyrofentanyl, butyrofentanyl, carfentanil, 3-methylcarfentanil, 4-fluorofentanyl, β-hydroxyfentanyl, α-methylfentanyl, cis-3-methylfentanyl, β-hydroxy-3-methylfentanyl, remifentanil, sufentanil, 3-methylthiofentanyl, naloxone, naltrexone, cathinone, 3,4-methylenedioxyamphetamine derivatives, aminoalkyl-substituted benzofurans, substituted amphetamines, aminoindane, diphenhydramine, hydrooxazine, phenylephrine, dopamine, epinephrine, lidocaine, oxymetazoline, chlormastine, chlorpheniramine, and 6-chloro-2-aminonaphthol. In some embodiments, the first pharmaceutical compound includes ketamine.

[0150] In some embodiments, the second pharmaceutical compound includes rapamycin. In some embodiments, the first pharmaceutical compound includes ketamine, and the second pharmaceutical compound includes rapamycin. In some embodiments, the first pharmaceutical compound does not include ketamine, and the second pharmaceutical compound includes rapamycin. In some embodiments, the second pharmaceutical compound includes clonidine. In some embodiments, the first pharmaceutical compound includes ketamine, and the second pharmaceutical compound includes clonidine. In some embodiments, the first pharmaceutical compound does not include ketamine, and the second pharmaceutical compound includes clonidine. In some embodiments, the chelating agent includes a substituted cyclodextrin. In some embodiments, the chelating agent includes 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 sulfobutyl ether-β-cyclodextrin. In some embodiments, a pharmaceutically acceptable salt is formulated for subcutaneous, intramuscular, sublingual, oral, rectal, vaginal, or intranasal administration. In some embodiments, the chelating agent includes a nonpolar region. In some implementations, the second drug compound complexes with the complexing agent via a nonpolar region.

[0151] In some embodiments, the first pharmaceutical compound includes a GABAergic agent, an α-2 agonist, an ophthalmic agent, a bisphosphonate, an antibiotic, an anticoagulant or thrombolytic agent, an antifungal agent, an antitumor drug, an antiviral agent, a cardiovascular drug, a central nervous system depressant, a central nervous system stimulant, a local anesthetic, an antiemetic, an antimigraine drug, an anti-Parkinson's disease drug, an antihistamine, an H2 histamine receptor blocker, an opioid, a tyrosine kinase inhibitor, or a combination thereof. In some embodiments, the antifungal agent includes an azole antifungal agent. In some embodiments, the first pharmaceutical compound includes a GABAergic agent. In some embodiments, the GABAergic agent includes baclofen, gaboxetine, or muscarinic acid, or a combination thereof. In some embodiments, the first pharmaceutical compound includes an α-2 agonist. In some embodiments, the α-2 agonist includes clonidine, guanifaxine, or tizanidine, or a combination thereof. In some embodiments, the first pharmaceutical compound includes an ophthalmic agent. In some embodiments, the ophthalmic agent includes acetylcholine, atropine, azelastine, brimonidine, cyclopentolate, ketotifen, levobunolol, olopatadine, pilucarpine, promecaine, tetracaine, timolol, or tropicamide, or combinations thereof. In some embodiments, the first pharmaceutical compound includes a bisphosphonate. In some embodiments, the bisphosphonate includes alendronate, ibandronate, pamidronate, risedronate, or zoledronic acid, or combinations thereof. In some embodiments, the first pharmaceutical compound includes an anticoagulant or thrombolytic agent. In some embodiments, the anticoagulant or thrombolytic agent includes alteplase, argatroban, bivalirudin, fondaparinux sodium, lepilostatin, streptokinase, or urokinase, or combinations thereof. In some embodiments, the first pharmaceutical compound includes an antitumor drug. In some embodiments, the antitumor drug includes bleomycin, busulfan, cisplatin, dacarbazine, daunorubicin, doxorubicin, epirubicin, etoposide, gemcitabine, idarubicin, ixaprilone, lapatinib, mesna, mitomycin C, paclitaxel, pemetrexed, rituximab, tesiromoxim, trastuzumab, venitoclax, or vincristine, or combinations thereof. In some embodiments, the first pharmaceutical compound includes a cardiovascular drug. In some embodiments, the cardiovascular drug includes brombenzylamine, dobutamine, dopexamine, eprostol, esmolol, iloprost, nesiritide, nitroglycerin, norepinephrine, or phenylephrine, or combinations thereof. In some embodiments, the first pharmaceutical compound includes a nervous system drug, such as a central nervous system drug. In some embodiments, the nervous system drug includes a central nervous system depressant. In some embodiments, the pharmaceutical composition includes a central nervous system stimulant. In some embodiments, the pharmaceutical composition comprises a central nervous system depressant, such as alprazolam, nitrazepam, clonazepam, diazepam, dexmedetomidine, dextromethorphan, flurazepam, gabapentin, ketamine, lorazepam, midazolam, oxazepam, propofol, temazepam, or triazolam or combinations thereof.In some embodiments, the first pharmaceutical compound includes a central nervous system drug, such as amphetamine, cocaine, dextromethorphan, dextroamphetamine, ephedrine, lysine amphetamine, methylamphetamine, methylphenidate, modafinil, phenylephrine, pseudoephedrine, sibutramine, or combinations thereof. In some embodiments, the first pharmaceutical compound includes a local anesthetic. In some embodiments, the local anesthetic includes articaine, benzocaine, bupivacaine, chloroprocaine, cocaine, dibutylcaine, eticaine, levobupivacaine, lidocaine, malbifocaine, prilocaine, procaine, imicaine, ropivacaine, or tetracaine, or combinations thereof. In some embodiments, the first pharmaceutical compound comprises an antiemetic. In some embodiments, the antiemetic includes dolasetron, granisetron, ondansetron, or palonosetron, or combinations thereof. In some embodiments, the first pharmaceutical compound includes an anti-migraine drug. In some embodiments, the anti-migraine drug includes amotriptan, avitriptan, doniptriptan, eletriptan, fultriptan, lamitantan, naratriptan, rizatriptan, sumatriptan, or zolmitriptan, or combinations thereof. In some embodiments, the first pharmaceutical compound includes an anti-Parkinson's disease drug. In some embodiments, the anti-Parkinson's disease drug includes amantadine, apomorphine, benzalkonium chloride, bromhexine, cabergoline, carbidopa, entacapone, foscarbidopa, foscarbidopa, levodopa, levodopa, melatonin, pramipexole, rasagiline, ropinirole, rotigotine, safenamide, selegiline, tocapone, or trihexyphenidyl, or combinations thereof. In some embodiments, the first pharmaceutical compound includes an antihistamine. In some embodiments, the antihistamine includes avastin, brompheniramine, cetirizine, chlorpheniramine, clomastine, cyproheptadine, desloratadine, dextrochlorpheniramine, diphenhydramine, doxylamine, fexofenadine, hydroxyzine, levocetirizine, loratadine, meclomethasone, promirtine, or tropineamine, or combinations thereof. In some embodiments, the first pharmaceutical compound includes an H2 histamine receptor blocker. In some embodiments, the H2 histamine receptor blocker includes cimetidine, famotidine, nizatidine, or ranitidine, or combinations thereof. In some embodiments, the first pharmaceutical compound includes an inhibitor, such as a tyrosine kinase inhibitor, like bosutinib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, ponatinib, sorafenib, or sunitinib, or combinations thereof. In some embodiments, the first pharmaceutical compound includes amipyridine, amifostine, aminocaproic acid, argatroban, asenapine, atropine, bivalirudin, cisatracurium, deferoxamine, desmopressin, gabapentin, lurasidone, milrinone, nicotine, octreotide, pregabalin, rocuronium bromide, terbutaline, tirofiban, tranexamic acid, vecuronium bromide, or naprafenamide, or combinations thereof.

[0152] In some embodiments, the solubility of the second drug compound in a pharmaceutically acceptable salt is higher than that of the second drug compound as a salt, wherein the second drug compound has the same concentration in both the pharmaceutically acceptable salt and as a salt. In some embodiments, the solubility of the second drug compound in a pharmaceutically acceptable salt is increased by at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, or 100 times compared to its solubility as a salt, wherein the second drug compound has the same concentration in both the pharmaceutically acceptable salt and as a salt.

[0153] In some embodiments, the plurality of acidic functional groups include an acidic group that acts as a counterion of the protonated nitrogen atom of the pharmaceutical compound. In some embodiments, the acidic group is a conjugate base of the acidic group. In some embodiments, the acidic group is a carboxylic acid or a carboxylate. In some embodiments, the acidic group is a carboxylate. In some embodiments, the acidic group is a sulfonic acid or a sulfonate. In some embodiments, the acidic group is a sulfonate. In some embodiments, the conjugate base of the complexing agent acts as a counterion of the plurality of pharmaceutical compounds. In some embodiments, each of the plurality of acidic functional groups acts as a counterion of the plurality of pharmaceutical compounds. In some embodiments, each of the plurality of acidic functional groups acts as a counterion of the protonated amine of the plurality of pharmaceutical compounds. In some embodiments, each of the plurality of acidic functional groups acts as a counterion of the protonated amine.

[0154] In some embodiments, the complexing agent is a cyclodextrin substituted with multiple acidic functional groups. In some embodiments, the multiple acidic functional groups are carboxylic acids, sulfonic acids, phosphonic acids, or any combination thereof. In some embodiments, the cyclodextrin is substituted with at least one, at least two, at least three, at least four, at least five, or at least six acidic functional groups. In some embodiments, the cyclodextrin is substituted with 3 to 8, 3 to 7, 4 to 8, 4 to 7, 5 to 8, 6 to 8, or 7 to 8 acidic functional groups.

[0155] In some embodiments, the complexing agent is a substituted cyclodextrin. In some cases, the substituted cyclodextrins provided herein are complex mixtures in which individual cyclodextrin molecules may contain a different number of substituents than other individual cyclodextrin molecules. In such cases, the number of substituents (e.g., the number of acidic functional groups) described on the cyclodextrins provided herein may refer to the average degree of substitution of the mixture. For example, when a cyclodextrin is described as being substituted with 3 to 8 acidic functional groups, it is intended to cover complex mixtures of cyclodextrins having an average degree of substitution of 3 to 8 acidic functional groups. The average degree of substitution need not be an integer value, but is typically a decimal value. For example, the average degree of substitution of commercially available SBEBCD is about 6.5.

[0156] In some embodiments, the complexing agent is a substituted cyclodextrin. In some embodiments, the substituted cyclodextrin is replaced by one or more acidic functional groups or pharmaceutically acceptable salts thereof. In some embodiments, the substituted cyclodextrin is replaced by multiple carboxylic acid, sulfonic acid, phosphonic acid, or phosphonic acid functional groups. In some embodiments, the cyclodextrin is replaced by at least one, at least two, at least three, at least four, at least five, or at least six acidic functional groups. In some embodiments, the cyclodextrin is replaced by 3 to 8, 3 to 7, 4 to 8, 4 to 7, 5 to 8, 6 to 8, or 7 to 8 acidic functional groups.

[0157] In some embodiments, the molar ratio of cyclodextrin to the pharmaceutical compound containing a protonated nitrogen atom is from about 1:4 to about 1:8. In some embodiments, the molar ratio of cyclodextrin to the pharmaceutical compound containing a protonated nitrogen atom is from about 1:4 to about 1:10. In some embodiments, the molar ratio of cyclodextrin to the pharmaceutical compound containing a protonated nitrogen atom is from about 1:5 to about 1:7. In some embodiments, the molar ratio of cyclodextrin to the pharmaceutical compound containing a protonated nitrogen atom is about 1:4. In some embodiments, the molar ratio of cyclodextrin to the pharmaceutical compound containing a protonated nitrogen atom is about 1:5. In some embodiments, the molar ratio of cyclodextrin to the pharmaceutical compound containing a protonated nitrogen atom is about 1:6. In some embodiments, the molar ratio of cyclodextrin to the pharmaceutical compound containing a protonated nitrogen atom is about 1:7. In some embodiments, the molar ratio of cyclodextrin to the pharmaceutical compound containing a protonated nitrogen atom is about 1:8. In some embodiments, the molar ratio of cyclodextrin to the pharmaceutical compound containing a protonated nitrogen atom is about 1:9. In some embodiments, the molar ratio of cyclodextrin to the pharmaceutical compound containing a protonated nitrogen atom is about 1:10.

[0158] In some embodiments, the molar ratio of the acidic functional group of the chelating agent to the pharmaceutical compound containing a protonated nitrogen atom is from about 2:1 to about 1:2. In some embodiments, the molar ratio of the acidic functional group of the chelating agent to the pharmaceutical compound containing a protonated nitrogen atom is from about 1.75:1 to about 1:1.75. In some embodiments, the molar ratio of the acidic functional group of the chelating agent to the pharmaceutical compound containing a protonated nitrogen atom is from about 1.5:1 to about 1:1.5. In some embodiments, the molar ratio of the acidic functional group of the chelating agent to the pharmaceutical compound containing a protonated nitrogen atom is from about 1.4:1 to about 1:1.4. In some embodiments, the molar ratio of the acidic functional group of the chelating agent to the pharmaceutical compound containing a protonated nitrogen atom is from 1.3:1 to about 1:1.3. In some embodiments, the molar ratio of the acidic functional group of the chelating agent to the pharmaceutical compound containing a protonated nitrogen atom is from about 1.25:1 to about 1:1.25. In some embodiments, the molar ratio of the acidic functional group of the complexing agent to the pharmaceutical compound containing a protonated nitrogen atom is from about 1.2:1 to about 1:1.2. In some embodiments, the molar ratio of the acidic functional group of the complexing agent to the pharmaceutical compound containing a protonated nitrogen atom is from about 1.15:1 to about 1:1.15. In some embodiments, the molar ratio of the acidic functional group of the complexing agent to the pharmaceutical compound containing a protonated nitrogen atom is from about 1.1:1 to about 1:1.1. In some embodiments, the molar ratio of the acidic functional group of the complexing agent to the pharmaceutical compound containing a protonated nitrogen atom is from about 1.05:1 to about 1:1.05. In some embodiments, the molar ratio of the acidic functional group of the complexing agent to the pharmaceutical compound containing a protonated nitrogen atom is about 1:1.

[0159] In some implementations, cyclodextrin is a compound of formula (I): (I); in: Each R 1 It is independently an H or optionally substituted alkyl group; Each R 2 Independently, it is an H or optionally substituted alkyl group; and n is 6, 7, or 8; Or its stereoisomers, mixtures of stereoisomers or isotopic variants; or its pharmaceutically acceptable salts, solvates or hydrates.

[0160] In some implementations, each R 1 Alkyl groups are independently H or optionally substituted with polar functional groups. In some embodiments, the polar functional group is an amide functional group, an acid functional group, an ester functional group, a hydroxyl functional group, an alkoxy functional group, or a poly(epoxy) functional group. In some embodiments, each R 1Alkyl groups that are independently H or optionally substituted with acidic or hydroxyl functional groups.

[0161] In some implementations, each R 1 Alkyl groups that are independently H or optionally substituted with acidic functional groups. In some embodiments, each R... 1 Independently, it is an H or an alkyl group substituted with an acidic functional group. In some embodiments, each R... 1 Independently H or a C1-C6 alkyl group substituted with an acidic functional group. In some embodiments, each R 1 Independently, it is an H or a C1-C6 alkyl group substituted with an acidic functional group selected from carboxylic acids, sulfonic acids, phosphonic acids, or phosphonic acids. In some embodiments, each R... 1 H independently , , , , , , , , , , or In some implementations, each R 1 H independently , , , or In which R 1 In some implementations that include acidic functional groups, each R 2 It is either H or acetyl. R is present in this group. 1 In some implementations that include acidic functional groups, each R 2 For H.

[0162] In some implementations, each R 1 Alkyl groups that are independently H or optionally substituted with hydroxyl functional groups. In some embodiments, each R 1 Independently, it is an H or an alkyl group substituted with a hydroxyl functional group. In some embodiments, each R... 1 Independently, it is an H or a C1-C6 alkyl group substituted with a hydroxyl functional group. In some embodiments, each R... 1 Independently, it may be H or hydroxypropyl, hydroxybutyl, hydroxypentyl, or hydroxyhexyl. In some embodiments, each R... 1 and R 2 It can be H or hydroxypropyl, hydroxybutyl, hydroxypentyl or hydroxyhexyl independently.

[0163] In some implementations, each R 2Alkyl groups that are independently H or optionally substituted with polar functional groups. In some embodiments, each R... 2 Independently, it is an H or an alkyl group optionally substituted with a hydroxyl functional group. In some embodiments, each R 2 Independently, it is an H or an alkyl group substituted with a hydroxyl functional group. In some embodiments, each R... 2 Independently, it is an H or a C1-C6 alkyl group substituted with a hydroxyl functional group. In some embodiments, each R... 2 Independently, it may be H or hydroxypropyl, hydroxybutyl, hydroxypentyl, or hydroxyhexyl. In some embodiments, each R... 2 It is H. In some implementations, each R 2 It is H or acetyl.

[0164] In some implementations, each R 2 Alkyl groups that are independently H or optionally substituted with acidic functional groups. In some embodiments, each R... 2 Independently, it is H or a C1-C6 alkyl group optionally substituted with an acidic functional group. In some embodiments, each R 2 It is a C1-C6 alkyl group that is independently H or optionally substituted with a sulfonic acid or carboxylic acid functional group.

[0165] In some implementations, n is 6 or 7. In some implementations, n is 7 or 8. In some implementations, n is 6. In some implementations, n is 7. In some implementations, n is 8.

[0166] In some implementations, the cyclodextrin is SBEBCD.

[0167] On the one hand, this article provides pharmaceutically acceptable salts of drug compounds having the following formula. [A] a [B] Wherein: A is a pharmaceutical compound containing at least one basic nitrogen atom, wherein the pharmaceutical compound is an antiviral compound, an antibacterial compound, an antifungal compound, a compound for treating neurological disorders, a compound for treating Parkinson's disease, a treatment for migraines, a treatment for autoimmune diseases, a treatment for cancer, a treatment for lymphoma, a treatment for pancreatitis, a treatment for opioid overdose, a treatment for influenza infection, or a treatment for inflammatory disorders. In some embodiments, the pharmaceutical compound includes rotigotine, eletriptan, DXM, copanlixetine, remdesivir, nafamostat (nafamostat mesylate), midazolam, levodopa, tigecycline, naloxone, amikacin, 1-amantadine, 2-amantadine, rimantadine, amipridine, rapamycin, clonidine, or caspofungin; B is a complexing agent comprising a plurality of acidic functional groups; and a is a number from 1 to 5, wherein the number is selected such that a portion (but not all) of the acidic functional groups of B acts as a counterion to the total number of basic nitrogen atoms of A, and the total number of basic nitrogen atoms of A is less than the number of acidic functional groups of B. In some embodiments, the pKa of A is at least 1. In some embodiments, the pKa of A is 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, or about 1 to about 2. In some embodiments, B interacts with a monovalent cation. In some implementations, the monovalent cation includes Na. + K + H + Li + Or a combination of or two or more of them.

[0168] In some implementations, B further includes a nonpolar region. B acts as a counterion between 1 to 4 drug compound molecules.

[0169] In some embodiments, the pharmaceutically acceptable salt contains about 1 molar equivalent of the drug compound compared to the amount of the complexing agent, and the about 1 molar equivalent of the drug compound is unionized and complexes with the complexing agent through a nonpolar region.

[0170] B can be any complexing agent provided herein, including but not limited to any cyclodextrin or compound of formula (I) provided herein, the number of acidic groups of such compounds affecting the value of a.

[0171] In some embodiments, the solubility of the drug compound in a pharmaceutically acceptable salt is higher than (i) the solubility of the drug compound as a salt; or (ii) the solubility of the drug compound complexed with a nonpolar pore of a complexing agent in a salt containing the drug compound in its free base form, wherein the drug compound has the same concentration in the pharmaceutically acceptable salt, the drug compound as a salt, and the salt containing the drug compound in its free base form. In some embodiments, the solubility of the drug compound in a pharmaceutically acceptable salt is higher than the solubility of the drug compound in a salt containing a drug compound with a higher molar ratio to a complexing agent and the drug compound in a complexing agent, wherein the drug compound has the same concentration in both the pharmaceutically acceptable salt and the salt containing the drug compound with a higher molar ratio to a complexing agent. In some embodiments, the solubility of the drug compound in a pharmaceutically acceptable salt is increased by at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, or 100 times compared to (i) the solubility of the drug compound as a salt; or (ii) the solubility of the drug compound in a salt containing the drug compound in the form of a free base, wherein the drug compound has the same concentration in the pharmaceutically acceptable salt, the drug compound as a salt, and the salt containing the drug compound in the form of a free base. In some embodiments, the solubility of the drug compound in a pharmaceutically acceptable salt is increased by at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, or 100 times compared to the solubility of the drug compound in a salt containing a high molar ratio of the drug compound to the complexing agent, wherein the drug compound has the same concentration in both the pharmaceutically acceptable salt and the salt containing a high molar ratio of the drug compound to the complexing agent.

[0172] A can be any pharmaceutical compound provided herein, the properties of which (e.g., the number of basic nitrogen atoms) will affect the value of the subscript a. In some cases, the pharmaceutical compound may contain multiple basic nitrogen atoms, one or more of which (but not necessarily all) may be considered basic. In some embodiments, the pharmaceutical compound includes ionizable nitrogen. In some embodiments, the pharmaceutical compound includes ionizable nitrogen, and the pKa of the pharmaceutical compound is at least 1. In some embodiments, at least one basic nitrogen atom comprises any nitrogen of the pharmaceutical compound having a pKa of at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, or at least 11.

[0173] The value of 'a' does not need to be an integer. For example, if the complexing agent B acts as a counterion for 2.5 molecules of drug compound A, each of which contains two protonated nitrogen atoms, then the structure of the entire salt complex will result in the charged A molecules being effectively "shared" between the B molecules.

[0174] Furthermore, any complexing agent B need not be of the same class with identical substitutions of acidic functional groups, and this disclosure expressly anticipates that this is generally not the case. For example, commercially available SBEBCD has an average degree of substitution of about 6.5 acidic functional groups. In this case, it has formula [A]. a The compound [B] is designed to cover this heterogeneous complexing agent mixture.

[0175] In some embodiments, pharmaceutical compound A comprises one, two, or three basic nitrogen atoms. In some embodiments, pharmaceutical compound A comprises one basic nitrogen atom. In some embodiments, pharmaceutical compound A comprises two basic nitrogen atoms. In some embodiments, pharmaceutical compound A comprises three basic nitrogen atoms.

[0176] In some embodiments, B comprises about 1 to about 8 acidic functional groups. In some embodiments, B comprises about 1 to about 2, about 1 to about 3, about 1 to about 4, about 1 to about 5, about 1 to about 6, about 1 to about 7, about 1 to about 8, about 2 to about 3, about 2 to about 4, about 2 to about 5, about 2 to about 6, about 2 to about 7, about 2 to about 8, about 3 to about 4, about 3 to about 5, about 3 to about 6, about 3 to about 7, about 3 to about 8, about 4 to about 5, about 4 to about 6, about 4 to about 7, about 4 to about 8, about 5 to about 6, about 5 to about 7, about 5 to about 8, about 6 to about 7, about 6 to about 8, or about 7 to about 8 acidic functional groups. In some embodiments, B comprises about 1, about 2, about 3, about 4, about 5, about 6, about 7, or about 8 acidic functional groups. In some embodiments, B comprises at least about 1, about 2, about 3, about 4, about 5, about 6, or about 7 acidic functional groups. In some embodiments, B comprises up to about 2, about 3, about 4, about 5, about 6, about 7, or about 8 aci...

Claims

1. A pharmaceutical composition comprising: (i) a pharmaceutical compound or its enantiomers, mixtures of enantiomers, or isotopic variants, 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, the plurality of acidic functional groups comprising acidic groups that act as counterions to the protonated nitrogen atom of the pharmaceutical compound. The molar ratio of the complexing agent to the pharmaceutical compound in the pharmaceutical composition is from about 1:1 to about 1:

10.

2. A pharmaceutical composition comprising: (i) a pharmaceutical compound, its enantiomers or isotopic variants, 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, the plurality of acidic functional groups comprising acidic groups that act as counterions to the protonated nitrogen atom of the pharmaceutical compound. The molar ratio of the complexing agent to the pharmaceutical compound in the pharmaceutical composition is from about 1:1 to about 1:

10.

3. A pharmaceutical composition comprising: (i) a pharmaceutical compound or its enantiomers, mixtures of enantiomers, or isotopic variants, 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, the plurality of acidic functional groups comprising acidic groups that act as counterions to the protonated nitrogen atom of the pharmaceutical compound. The molar ratio of the complexing agent to the pharmaceutical compound in the pharmaceutical composition is from about 1:1 to about 1:

10.

4. A pharmaceutical composition comprising: (i) a pharmaceutical compound or its enantiomers, mixtures of enantiomers, or isotopic variants, 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, the plurality of acidic functional groups comprising acidic groups that act as counterions to the protonated nitrogen atom of the pharmaceutical compound. The molar ratio of the complexing agent to the pharmaceutical compound in the pharmaceutical composition is from about 1:1 to about 1:

10.

5. The pharmaceutical composition according to 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 agent comprises 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 according to any one of claims 1-7, wherein the cyclodextrin is sulfobutyl ether-β-cyclodextrin (SBEBCD).

9. The pharmaceutical composition according to any one of claims 1-8, wherein the pKa of the pharmaceutical compound is at least 1.

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

5.

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

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

13. The pharmaceutical composition of any one of claims 1-12, wherein the pharmaceutical compound comprises 5'-deoxyribonucleoside, 6,7-benzomorphine, amaryl-snake root alkaloid, alkaline earth metal organometallic compound, amaryllidium alkaloid, anthracene, anthracene ring, apophene, azaspirodecane, azacycloheptane, azobenzene, azole, azoleidine, azolinium, benzo[a]azine, benzene and substituted benzene, benzimidazole ribonucleoside and ribonucleotide, benzimidazole, benzo[a]cycloheptylpyridine, benzo[a]diazazepine, benzo[a]dioxane, benzo[a]dioxane, benzo[a]dioxane, benzo[a]furan, benzo[a]pyran, benzo[a]pyrazole, benzo[a]thiadiazole, benzo[a]thiazide, benzo[a]thiazide, Benzothiazole, benzothiocyanate, benzothiophene, benzothiaran, benzotriazole, benzoxadiazole, benzooxazine, benzoxazine, benzooxazine, biotin, camptothecin, carboxylic acid, Cephalotaxus alkaloids, cinchona alkaloids, cinnamic acid, coumaranthium, cycloheptaphene, condensed phenolic acids and condensed phenolic acid cyclic ethers, diarylheptane compounds, diazanaphthalene, diazacyclohexane, diazine, dibenzocycloheptenene, dioxane, epoxides, ergoline, fatty acyl groups, flavonoid nucleotides, flavonoids, fluorene, furan, furanopyran, glycerophospholipids, other homogeneous nonmetallic compounds, hydroxy acids, ibogan-type alkaloids, imidazodiaza, imidazoribose Nucleosides and ribonucleotides, imidazopyridine, imidazopyrimidine, imidazothiazole, indene, indene and isindene, indole, indolizidine, isocoumaranth, isoindole, isoquinoline, lactam, linear 1,3-diarylpropane, lupin alkaloids, macrolactams, macrolide lactams, macrolide morphine, tetraphenyl, naphthalene, naphthofuran, naphthopyran, nucleosides and nucleotide analogs, organic carbonic acid, organophosphoric acid, organophosphonic acid, organic nitrogen compounds, organic oxygen compounds, organothiophosphoric acid compounds, oxazine, peptide analogs, phenanthrene, phenanthroline, phenol esters, phenol ethers, phenol, phenylpropionic acid, phthaloylisoquinoline, piperazinezazazo ... Pyridine, polypeptide, isopentenol lipid, pteridine, purine nucleoside, purine nucleotide, pyrazolopyridine, pyrazolopyrimidine, pyridine, pyridopyrimidine, pyrimidine nucleoside, pyrrole, pyrrolidine, pyrrolopyrazine, pyrrolopyridine, pyrrolopyrimidine, quinoline, steroids and steroids, piracetam, tetracycline, tetrahydroisoquinoline, naphthiazine, thienodiazazine, thienopyridine, thienothiazine, thiochromene, thioether, thiol, thiophene, transition metal salts, triazacyclohexane, triazine, triazole ribonucleoside and ribonucleotide, triazole pyrimidine, triphenyl compounds, hyoscyamine alkaloids, vinca alkaloids, yohimbine alkaloids or their derivatives or combinations thereof.

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

15. The pharmaceutical composition of claim 14, wherein the pharmaceutical compound comprises 1,4-benzodiazepine, amine, amino acid, peptide, androstened steroid, benzenesulfonamide, benzoic acid, benzophenone, benzothiadiazine, biphenyl, carboxylic acid derivative, phenolic peptide, diphenylmethane, ether, halobenzene, isoindoline, nitrogen mustard compound, nitroquinoline, purine 2'-deoxyribonucleoside, purine, pyrazole, pyrimidine or derivative thereof, retinoid, substituted pyrrole or combinations thereof.

16. The pharmaceutical composition of claim 15, wherein the pharmaceutical compound comprises apatideson, asunaprevir, azilsartan medoxomil, benzylthiazide, bromfenac, candesartan medoxomil, epinephrine, chlorambucil, chlorothiazide, cladribine, clofarapine, clonazepam, CVT-6883, CX516, dacarbazine, diazoxide, ammodendron, femasartan, flubendazole, flucytosine, fludiazepam, flunitrazepam, ganciclovir, gliclazide, glimepiride, grapravir, guanosine, isotetrast, Isobutrol, iodophoric acid, iopamidol, iodophoric acid, essatoribine, ixazomib, MB-07803, nateglinide, nepafenamide, OPC-51803, praconazole, pomalidomide, punicaxin, pyrimidine, rimonaban, selexipar, smetapivir, sulfadimethoxypyrimidine, sulfamethoxypyrimidine, sulfamethazine, sulfamethoxazole, sulfamethoxazole, sulfadiazine, sulfamethoxazole, sulfadiazine, sulfamethoxazole, tiranaban, tazarotene, thiopronin, tolazoline, tramidil, uracil nitrogen mustard, or combinations thereof.

17. The pharmaceutical composition of any one of claims 1-11, wherein the pKa of the pharmaceutical compound is about 2 to about 3.

18. The pharmaceutical composition of claim 17, wherein the pharmaceutical compound comprises azobenzene, azole, benzodiazepine, benzene, benzodiazepine, benzothiazine, benzothiazolium, carboxylic acid, phenolic acid, diazonium, diazine, imidazopyrimidine, indole, isoindole, lactam, macrolide naphthalene, nucleoside and nucleotide analog, organic oxygen compound, piperidine, isopentenyl alcohol lipid, pteridine, purine nucleoside, purine nucleotide, pyrazolopyrimidine, pyridine, pyrimidine nucleoside, pyrrolopyridine, quinoline, steroid, thienodiazepine, triazine, triazolopyrimidine or combinations thereof.

19. The pharmaceutical composition of claim 18, wherein the pharmaceutical compound comprises 1,4-benzodiazepine, amino acid or peptide, aminotriazine, androstened steroid, acetanilide, aniline and substituted aniline, benzodiazepine, benzenesulfonamide, benzenesulfonyl compound, benzodiazepine, benzoic acid and derivatives, β-lactam, biphenyl and derivatives, carbazole, diphenyl ether, diphenylmethane, epothilone estradiol, ether, halobenzene, isoindoline, milbemycin, monoterpenoid, nitroquinoline and derivatives, oxosteroid, phenoxyacetic acid derivative, phenylbutylamine, phenylcarbamate, benzylamine, phenylpropane, phenylquinoline, pterin and derivatives, purine 2',3'-dideoxyribonucleoside, purine ribonucleotide, purine and purine derivatives, pyrazole, pyrazolo[3,4-d]pyrimidine, pyridine carboxylic acids and derivatives, pyrimidine and pyrimidine derivatives, sulfonylacetamide or combinations thereof.

20. The pharmaceutical composition of claim 18 or 19, wherein the pharmaceutical compound comprises acyclovir, adecidyllon, allistois, allopurinol, ambrisentan, amerubent, aminobenzoic acid, aminopterin, aminosalicylic acid, ampravir, anastrozole, para-aminobenzoic acid, asoprilinide, benzocaine, BMS-488043, becanavir, bromazepam, bumetanide. Butanol, cangreloxol, cefixime, cefpirome, chromium pyridinecarboxylate, cidofovir, cilupvir, sennatastat, clarsentan, clotrazepam, chloroxazolam, dabrafenib, dapsone, darunavir, dillazepam, diazepam, doxorubicin, dutasteride, edotecan, edofodipine, ecirapine, entecavir, ipilazole, epothilone D, finasteride, fluconazole, flumetfon ( 18 F), Folic acid, metoprolol, fosanavir, ganstigmine, GW-501516, halazepam, indocyanine green, inosine, iodamide, iopromide, essaconazole, ixaspirin, KOS-1584, KP-1461, lenalidomide, letrozole, folinic acid, levofolinic acid, macitentan, meladidone, mercaptopurine, methotrexate, methylene blue, methylthionine, motexafen gadolinium, motexafen luteolin, moxifloxacin, naciline, nitrazepam, nitrohydroxyquinoline, olaparib, olbitahim, OT-551, pardimethicone O, pariprevir, parupilone, penciclovir, aminosalicylic acid phenyl ester PPL-100, pralatrexate, quazepam, rivconazole, regorafenib, regreroline, ritonavir, roflumilast, roxadustat, silver sulfadiazine, sorafenib, stanozolol, sulfabenzoyl, sulfacetyl, sulfaxitin, sulfadiazine, sulfadoxine, sulfamethazine, sulfadiazine, sulfamethazine, sulfabenzopyrazole, sulfapyridine, sulfasalazine, sulfathiazole, sulfisoxazole, tannetan, tasosartan, technetium[99mTc]desofenine, technetium[99mTc]methylbromofenmin, tezosentan, ticagrelor, terazamine, trisatabine, trypan blue, voriconazole or combinations thereof.

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

22. The pharmaceutical composition of claim 21, wherein the pharmaceutical compound comprises 1,4-benzodiazepine, amino acids, peptides, acetanilide, aniline and substituted aniline, anisole, aryl thioether, benzodiazepine, benzofuranone, benzoic acid and derivatives, benzophenone, β-lactam, biphenyl and derivatives, bipyridine and oligopyridine, carbodiimide, diphenyl ether, diphenylmethane, epothilone estradiol, ether, haloquinoline, hexacarboxylic acid and derivatives, imidazole, isoindole, milbemycin, morpholine, phenoxyacetic acid derivatives, benzylamine, phenylpyridine, piperazine, pterin and derivatives, purine 2',3'-dideoxyribonucleoside, purine and purine derivatives, purine and purine derivatives, pyrazine, pyrazole, pyridine carboxaldehyde, pyridine carboxylic acid and derivatives, pyridine sulfonamide, pyridyltriazole, steroid esters, sulfonyl acetanilide, sulfinylbenzimidazole or combinations thereof.

23. The pharmaceutical composition of claim 21 or 22, wherein the pharmaceutical compound comprises adenosine, amiloride, aminobenzoic acid, aminopyrine, anagrelide, aprepitant, para-aminobenzoic acid, azathioprine, aztreonam, benzocaine, benzonatate, diacetylbenzoic acid, bromazepam, bromotezolam, bumetanide, butanben, calcium cyanamide, cefepime, cefixime, cefotaxime, cefotaxime, cefpodoxime, cefazolin, ceftriaxone, chlorhexidine, chromium pyridinecarboxate, cloiodohydroxyquine, dabigatran etexilate, dabrafenib, dexlansoprazole, dexrazoxen, diazepam, norinosine, diiodohydroxyquinoline, entecavir, etofibrate, itravirine, ezogabaline, flumazenil, flumetazidine ( 18 F), Indigo, Inosine, Nicotinic Acid Inositol Ester, Iophobic Acid, Irbesartan, Iscarbohydrazine, Isoniazid, Itraconazole, Ixaspirone, Lansoprazole, Leucovorin, Levofolinic Acid, Rosiglitazone, Losartan, Lumacartocin, Maindo, Mebendazole, Mercaptopurine, Mercaptopurine, Methotrexate, Metronidazole, Montelukast, Montelukast, Moxifloxacin, Nerapine, Nicotinic Acid, Nicotinamide, Norgestrel, Norgestrel, Olfendazole Padimamate, pantoprazole, penciclovir, perampanel, picosulfate, piroxicam, posaconazole, pralatrexate, pralatrexam, procaine ethoxymercurin, pyridoxal, pyridoxal phosphate, riociguat, ritonavir, stanozolol, tanidazole, tasosartan, tenofovir disoproxil fumarate, thiabendazole, tonazolium, ticagrelor, tinidazole, thioguanine, topiroxetine, torasemide, triamterene, triamterene, vemurafenib, vemurafenib, vemodilide, or combinations thereof.

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

25. The pharmaceutical composition of claim 24, wherein the pharmaceutical compound comprises 1,4-benzodiazepine, 1-ribosyl-imidazolium carbamate, 2-benzimidazolyl carbamate, 8-hydroxyquinoline, amine, amino acid, peptide, androstened steroid, acetanilide, aniline and substituted aniline, anthraquinone, aryl sulfide, benzodiazepine, benzoic acid and derivatives, β-lactam, biphenyl and derivatives, bipyridine and oligopyridine, bisphosphonate, carbonyl compound, di... Benzene, ethers, hexacarboxylic acids and their derivatives, imidazoles, imidazoquinolines, indolequinones, naphthidines, oxosteroids, phenethylamine, phenylbenzimidazoles, phenylhydrazines, phenylpiperidines, phenylpyridines, phenylquinolines, pterin and their derivatives, purine ribonucleotides, purines and purine derivatives, pyrazolo[1,5-a]pyrimidines, pyridine carboxylic acids and their derivatives, pyridine sulfonamides, pyridoindole, quinoline carboxylic acids, styrene, sulfinylbenzimidazoles, trifluoromethylbenzene or combinations thereof.

26. The pharmaceutical composition of claim 24 or 25, wherein the pharmaceutical compound comprises azathioprine, abiraterone, acalcein, 5'-adenosine sulfate, adenosine monophosphate, AICA ribonucleotide, albendazole, amphetalil, aminoglutethimide, aminohippuric acid, amrinone, atazanavir, aztreonam, banoxane, pinenodipine, diacetylphenidate, carfilzomib, cefotaxime, cefepime, cefotaxime, cefotaxime, cefpodoxime, ceftazidime, cefbufen, cefazolin, cefazolin, ceftriaxone, coenzyme A, dexlansoprazole, ensolazole, erlotinib, emeprazole, estazolam, etomidate, etomidate, ethorcoxib, itravirin, feboraben, flavin adenine dinucleotide, flubetaban ( 18 F), flubetapyr ( 18 F), Gerdemycin, Gentian Violet, Hexocyram, Adelalipic Acid, Impetatae, Indium In-111 Oxyquinoline, Nicotinic Acid Inositol Ester, Iophobic Acid, Irbesartan, Lansoprazole, Levosimendan, Loratadine, Lornoxicam, Losartan, LX-2931, Methoxyamine, Metheprone, Mifepristone, Milrinone, Minoxidil, Nafidinic Acid, Nicotinic Acid, Osiprolone, Omeprazole, OSI-930, Oxyquinoline, Perampanel, Pilidisone, Picosulfate ... Vastatin, limonin, PX-12, pyridoxal, pyridoxal phosphate, rabeprazole, repaglinide, riquimod, retamycin, lidogre, riluzole, risedronate, linaglitone, rosofloxacin, S-8510, sapropterin, ticardisone, tenofovir disoproxil fumarate, tenoxicam, thiabendazole, torasemide, triazolam, tucistat, uristat, varitinib, valproinib, verteporfen, velurubin, vidarabine, velpatinam, vorapazol, or combinations thereof.

27. The pharmaceutical composition of any one of claims 1-11, wherein the pKa of the pharmaceutical compound is about 5 to about 6.

28. The pharmaceutical composition of claim 27, wherein the pharmaceutical compound comprises 1,4-benzodiazepine, 1-ribosyl-imidazolium carbamate, 2-benzimidazolyl carbamate, 8-hydroxyquinoline, amine, amino acid, peptide, androstened steroid, acetanilide, aniline and substituted aniline, anthraquinone, aryl sulfide, benzodiazepine, benzoic acid, β-lactam, biphenyl, bipyridine and oligopyridine, bisphosphonate, diphenylmethane. Ethers, hexacarboxylic acids, imidazoles, imidazoquinolines, indolequinones, naphthidines, oxosteroids, phenethylamine, phenylbenzimidazoles, phenylhydrazines, phenylpiperidines, phenylpyridines, phenylquinolines, pterin, purine ribonucleotides, purines and purine derivatives, pyrazolo[1,5-a]pyrimidines, pyridine carboxylic acids, pyridine sulfonamides, pyridoindole, quinoline carboxylic acids, styrene, sulfinylbenzimidazoles, trifluoromethylbenzene or their derivatives or combinations 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-methyltetrahydrofolate, abacavir, adefovir dipivoxil, adenine, alprazolam, ALT-2074, amadoxovir, apimod, adenosine triphosphate, avanafil, axitinib, azledipine, benazepril, benzimidazole, and bisacodyl. Bilicorice dicitrate, Brilliant Green, Cabozantinib, Capvirine, Carbidopa, Cefpiromeline, Cirivastatin, Cilapril, Cisplatin, Clonidipine, Clonisin, Clopidogrel, Cocarboxylase, Dapivirine, Desalazine, Dolastron, Elbasvir, Enalapril, Ethionamide, Etenofoline, Etozoline, Famciclovir, Felodipine, Fulofenone, Fosaspirin, GTS-21, Hitacitracin Lin, Imidacloprid, Imiquimod, Incardonic acid, Indebulin, Issubanlan, Iradipine, Kinetin, Lamotrigine, Leadipasvir, Lincitinib, Melanathan, Mesalazine, Urotropine, Moxipril, Mornifluoxetine, NADH, Nevirapine, Nifedipine, Nifluoxetine, Nimodipine, Nisodipine, Nifedipine, Olmesartan, Pazopanib, Pedesine, Perindopril, Phenylebhydrazine, Pyrapoplatin, Pinafenadil, Pioglitazone Pipercuronium bromide, pradefovir mesylate, prasugrel, prilinsta, procarbazine, pyridoxine, quinapril, ramipril, rilpivirine, ropepofen, ruxolitinib, celiac, sildenafil, sonodazole, spironolactone, sipofen, tapimod, tarivirine, temopril, temopofen, tenofovir alafenamide, thiamine, trandopril, tropicamide, velpatasvir, cimetidine, zinc pyridinecarboxate, zolpidem, or combinations thereof.

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

31. The pharmaceutical composition of claim 30, wherein the pharmaceutical compound comprises 1,4-benzodiazepine, 1-ribosyl-imidazolium carbamate, 2-benzimidazolyl carbamate, 8-hydroxyquinoline, amine, amino acid, peptide, androstened steroid, acetanilide, aniline and substituted aniline, anthraquinone, aryl sulfide, benzodiazepine, benzoic acid, β-lactam, biphenyl, bipyridine and oligopyridine, bisphosphonate, carbonyl compound, di... Benzene, ether, hexacarboxylic acid, imidazole, imidazoquinoline, indolequinone, naphthidine, oxosteroids, phenethylamine, phenylbenzimidazole, phenylhydrazine, phenylpiperidine, phenylpyridine, phenylquinoline, pterin, purine ribonucleotides, purines and purine derivatives, pyrazolo[1,5-a]pyrimidine, pyridine carboxylic acid, pyridine sulfonamide, pyridoindole, quinoline carboxylic acid, styrene, sulfinylbenzimidazole, trifluoromethylbenzene or its derivatives or combinations thereof.

32. The pharmaceutical composition of claim 30 or 31, wherein the pharmaceutical compound comprises 2-amino-1-methyl-6-phenylimidozolo(4,5-b)pyridine, 5-methyltetrahydrofolate, abacavir, adefovir dipivoxil, adenine, alprazolam, ALT-2074, amdoxovir, apimod, avanafil, azoledipine, benazepril, benzimidazole, bisacodyl, pyricin Bicocortide, Brilliant Green, capvirline, carbidopa, cerivastatin, cisplatin, clopidogrel, cocarboxylase, dapoxetine, deramani, desarazine, dolasetron, elbasvir, enalapril, Etenofoline, Etozoline, Famciclovir, Felodipine, Fulofenin, Forminoben, Fosapitan, GTS-21, Hetacillin, Imidacloprid, Imiquimod, Incadronic acid, Indebulin, Isooflavin, Iradipine, Kinetin, Lamotrigine, Leadipasvir, Melanathan, Mesalazine, Urotropine, Moxipril, Mornifluoxetine, Nevirapine, Nifedipine, Nifluoxetine, Nimodipine, Nisodipine, Nifedipine, Olmesartan, Pazopanib, Pedesine, Perindopril, Phenylezil, Pyrapirocin, Pinafenadil, Piaglitazone, Piperacillin, Piperacillin, Piperacillin, Pradefovir Mesylate, Prasugrel, Prinstat, Procarbazine, Pyridoxine, Quinapril, Randex Mipril, Rilpivirine, Ropepoxetine, Ruxolitinib, Celicillin, Sildenafil, Sonicate, Ropril, Sipofen, Tapimod, Talivirine, Temopril, Temopoxetine, Tenofovir Acetonide, Thiamine, Qundopril, Topicamid, Velpatasvir, Cimetazidine, Zinc Pyridinecarboxate, Zolpidem, Acarbose, Amaryl, Acaratadine, Alfentanil, Alfuzosin, Amitriazine, Amisulpride, Amoxicillin, Ampicillin, Amrubicin, Triprofen, Aripiprazole, Asenapine, Atemexazole, Azapirol, Bambucil, Cefaclor, Cefadroxil, Cefdinir, Cefprozil, Cefalexin, Cefalexin, Librium, Chlorpyrifos The following are listed: dapoxetine, dasatinib, diethylamine benzophenone, domperidone, dazolidin, doxapram, doxazosin, drotavirine, iriconazole, ipramone, flavoxetine, flubancerine, flupiridine, midazoline, indinavir, ketamine, ketotifen, lapatinib, loxapine, mabifocaine, methacycline, mosonidin, nefazodone, olanzapine, ondansetron, benzotriazine, pimozide, promocaine, prazosin, quetiapine, ranolazine, rupatadine, spruitrin, terazosin, buphenazine, ticlopidine, tizanidine, tofacitinib, trazodone, trimethoprim, valacyclovir, valganciclovir, ziprasidone, or combinations thereof.

33. The pharmaceutical composition according to claims 2-9, wherein the pKa of the pharmaceutical compound is about 7 to about 8.

34. The pharmaceutical composition of claim 33, wherein the pharmaceutical compound comprises amaryl-snake root alkaloid, 1,4-benzodiazepine, 2,3,5-trisubstituted thiophene, alcohols and polyols, amines, amino acids or peptides, acetoaniline, anisole, benzodiazepine, benzo[a]arene, benzene, benzimazole, benzocycloheptapyridine, benzodiazepine, benzodiazepine, benzo[a]diazine, benzo[a]furan, benzoic acid, benzo[a]thiadiazole, benzene Benzotriazole, benzo[a]oxazine, benzo[a]oxazine, benzylamine, benzylisoquinoline, benzylpiperidine, β-lactam, biphenyl, carbazole, carbohydrates, carbonyl compounds, carboxylic acids, cycloheptaphene, diarylheptane compounds, diazanaphthalene, diazacyclohexane, diazine, dibenzocycloheptene, dibenzodiazepine, dibenzo[a]oxazine, dibenzo[a]oxazine, diphenylmethane, ergoline, yellow Ketones, flavonoids, halogenated benzenes, heteropeptides, hydrogenated pyridine, indene, indole, indoline, isoquinoline, isoquinoline ketones, lactams, linear diarylheptane compounds, lysergic acid, macrolactams, macrolide lactams, monoterpenoids, morpholine, n-acylpiperidine, n-alkylindole, tetraphenyl, naphthopyranone, naphthopyran, n-phenylurea, organic nitrogen compounds, organic oxygen compounds, oxazine, pentacarboxylic acids, peptide mimics, phenanthrene, Phenethylamine, phenol ether, benzylamine, phenylpiperidine, phenylhyoscyamine, piperazine, piperidine carboxylic acid, piperidine, polypeptide, isopentenol lipid, pyridazine and its derivatives, pyridine, pyrimidine 2'-deoxyribonucleoside, pyrimidine nucleoside, pyrimidine, quinoline carboxylic acid, quinoline, steroid ester, steroid, tetrabenzoquinone, tetracycline, tetrahydroisoquinoline, thienopyridine, thiophene, hyoscyamine alkaloids, xylene, yohimbine alkaloids or their derivatives or combinations thereof.

35. The pharmaceutical composition of claim 33, wherein the pharmaceutical compound comprises acarbose, amorol, acarboxidine, alfentanil, alfuzosin, aripiprazole, ampicillin, amoxicillin, hexamethylmelamine, altropane, axidiclofen, amdectinoxil, aminolevulinic acid, amisulpride, amoxicillin, ampicillin, amrubicin, triamcinolone, aripiprazole, asenapine, atemetazole, AV-412, azapirolone, azatadine, bamectin, barnidipine, benidipine, bifenproxetine, bleomycin, buprofenserin, branicline, buffentanil, bupivacaine, buspirone, calcipoproxetine, cariprazine, caspoxetine, cathinone, cefaclor, cephalosporin Amoxicillin, cefdinir, cefprozil, cefadroxil, cefalexin, cefotaxime, quineerythromycin, cetirizine, chlortetracycline, cilansetron, clozapine, dapoxetine, dapoxetine, dasatinib, diserpine, diethylamine benzophenone, domperidone, dazolamide, dovitinib, doxapram, doxazosin, doxycycline, drotavelin, edonepe, ilfluconazole, ethacridine, ergotamine, enzatolin, edetol, enalapril, enzatolin, edetolone, ergonovine, ergotamine, EVT-101, ezazostana, fanicolin, fiproxil fumarate, phenafloxacin, flavoxetine, flubancerine, flunarizine, flupyridamole, hexyl aminolevulinate, hydroxyzine, ellaprilin, ipraprazole, midazoline, indole Denavir, Josamycin, Ketamine, Ketotifen, Lapatinib, Larazotide, Lesopiraline, Levobupivacaine, Levocetirizine, Lidocaine, Linaloolide, Lofexidine, Cefaclor, Lopipiprazole, Loxapine, Lysergic acid diethylamide, Manidipine, Mepipiprazole, Mabivocaine, Methoxycycline, Methylaminolevulinate, Methylergonovine, Mesiergoline, Miglitol, Motishanib, Mosoni, Naloxone, Naluzotan, Nefazodone, Nettopitan, Olanzapine, Olanzapine, Ondansetron, Oxytetracycline, Palonosetron, Piperipelone, Benzotriazine, Phenoxybenzamine, Pirenzepine, Pilamycin, Pimetacin, Phenylephrine, Promocaine, Prazosin, Praflavamide, PRX -08066, Pyrimethamine, Quetiapine, RAF-265, Raloxifene, Ranolazine, Reboxetine, Remifentanil, Resinamine, Rifampin, Rifapentine, Rocuronium, Ropivacaine, Rupatadine, Safenamide, Saxagliptin, Sprotiline, SNX-5422, Solithiasis, Suvgoli, SUVN-502, Talacferrin α, Telithromycin, Terazosin, Butenaazin, Ticlopidine, Tilpifab, Tizanidine, Tofacitinib, Trabectedin, Trazodone, Trimethoprim, Temasoezoline, Valacyclovir, Valganciclovir, Valoxicoclovir, Vatocilitabine, Venecella, Voglibose, Yohimbine, Ziprasidone, Zosquid, or combinations thereof.

36. The pharmaceutical composition of claim 2, wherein the pKa of the pharmaceutical compound is about 8 to about 9.

37. The pharmaceutical composition of claim 36, wherein the pharmaceutical compound comprises 1-benzopyran, 1-benzothiaran, 1-phenyltetrahydroisoquinoline, alcohol, polyol, amine, amino acid, peptide, aminoquinoline and derivatives, androstened steroids, acetanilide, anisole, aryl sulfide, hydroquinone, benzylsulfonamide, benzo-1,4-dioxane, benzodiazepine, benzoic acid and derivatives, benzoquinoline, benzylamine, benzyl ether, benzylpiperidine, β-lactam, biphenyl and derivatives, carbazole, carbohydrates and carbohydrate conjugates, carbonyl compounds, carboxylic acid derivatives, phenolic peptides, dibenzo[a]azine, dibenzo[thio]azine, dibenzo[oxo]azine, diphenylacetonitrile, diphenylfuran, diphenylmethane, ether, fatty acids and conjugates, fentanyl, selenocyanide, etc. Amaryllidaceae alkaloids of the Amaryllidaceae family, halogenated benzenes, hydrogenated pyridines, imidazolines, indazoles, indoles, indo-quinoline, isoquinolineones and their derivatives, isoxazoline, lysergic acid and its derivatives, methoxybenzenes, monoterpenoids, morpholine, n-alkylindoles, naphthidine, oxadiazoles, pentacarboxylic acids and their derivatives, phenethylamine, phenothiazine, phenothiazine, phenoxy compounds, benzylamine, phenylnaphthalene, phenylpiperidine, phenylpropane, phenylpyridine, phenylpyrrolidine, phenylquinoline, piperazine, piperidine carboxylic acids and their derivatives, purines and purine derivatives, pyrimidines and pyrimidine derivatives, pyrrolylpyridine, quinoline carboxamide, quinoline carboxylic acids, styrene, substituted pyrroles, sulfonylaniline, tetracarboxylic acids and their derivatives, thiazoles, thiophene carboxylic acids and their derivatives, trifluoromethylbenzene, xylene or its derivatives or combinations thereof.

38. The pharmaceutical composition of claim 36 or 37, wherein the pharmaceutical compound comprises acepromethazine, acephenanol, ararubicin, avalastine, afatinib, afoxifene, aranoxin, amiodarone, amino-13, ammonium molybdate, aminonaphthylfentanyl, amorolfen, amoxapine, acridine, amicaine, anamoxapine, aniridine, apirin, acetonide, aclonidine, articaine, azoxifen, azimadolin, aspartame, astemizole, atrasentan, azelastine, azithritol, bedaquiline, benzylfentanyl, bosutinib, buriperazole, brimonidine, bromhexine, bukrazine, bupivacaine, bupivacaine, bupropion, buprofentanyl, caldarazole, captopril, carbimazole, carfentanil, carvedilol, etc. Cefminox, cefotiam, sigmavir, cevimeline, clocycline, cloprocaine, clopidogrel, chlorpheniramine I-131, cinnarizine, ciprofloxacin, cisapride, clarithromycin, chlorpheniramine, clomocycline, clonidine, clopidogrel, CNS-5161, cocaine, cyclopenicillin, cyproheptadine, cyclopentolate, cycloserine, cyproheptadine, dalaladiol, daunorubicin, DDP-225, demeclocycline, delencyclohexane, desvenlafaxine, dicyclovir, dihydroergotamine, diltiazem, dimethicone, diphenhydramine, diphenhydramine, diphenoxylate, diphenhydramine, dofetilide, donepezil, dotazolidin, doxorubicin, doxylamine, dralidopa, d-serine, dacronin, edetate, edivaxetine, irradiated erythromycin Keda, eletraptane, elegliflozin, emesostine, enoxacin, eperisone, epinastine, adrenaline, epirubicin, erythromycin, esoxepine, famotidine, fasudil, fentanyl, flupentixol, fluphenazine, flurazepam, frodisiac, frelinomycin B, gaboxetine, gadofosamide, galantamine, galafloxacin, gatifloxacin, gresartinib, glucosamine, glypromate, granisetron, glifloxacin, haloperidol, hydrocodone, hydromorphone, idarubicin, imatinib, imolamin, indium pentiate In-111, iroxadin, isominir, isoproterenol, isocetide, isocetide, isocetide, isocetide, isocetide, isocetide, isocetide, isocetide, itelamine, itopride, catomycin, lasoxifene, L-asparagine, zobufenozide Bicaine, Cobadone, Lincomycin, Lobeline, Lofentanil, Lomefloxacin, L-Threonine, Thianthrone, Lumapizoline, Lurasidone, LY-517717, Demamagazine, Masatinib, Meclozine, Mepiquatone, Mepiquatine, Mepiquatine, Mepiquatine, Mepiquatine, Midodrine, Miglucostat, Miglucostat, Mimosine, Minocycline, Moxicillin Naloxetine, Nebivolol, Nafenavir, Nicardipine, Nicergoline, Nicotine, Norepinephrine, Norfloxacin, Normethadone, Oxcarpiperone, Oxymethylfentanil, Ophenazine, Osimertinib, Obubucaine, Oxibutin, Oxycodone, Hydroxybenzylamine, Palfurapine, Palbociclib, Palpanidone, Palirodone, Pargiline, PBT-1033, PeritolinibTrisodium pentiate calcium, trisodium pentiate zinc, pentostatin, perphenazine, meperidine, p-flufentanyl, indole, fenmetrazine, bensulfuron-methyl, pimozide, pipampazone, pipexazol, piperoxithiazide, pyridinole, ponatinib, PPI-1019, pricaine, procaine, prochlorperazine, proflavin, promecaine, piperazine, propyrazole, propylthiazide, prooxycaine, protoprolol, prunasine Carpipride, PRX-07034, Quinolidone, Quinuprin, Rabemodil, Ranitidine, Rasagiline, Remasiamide, Remopride, Lenzapride, Rifabutin, Rifarazil, Relapade, Risperidone, Rivasidine, Robazotane, Lorapitane, Roxatidine Acetate, Saquinavir, Salfloxacin, Salizotan, Selegiline, Serine, Serindole, Sincalitone, Sitagliptin, Soriberi Naxin, Sparfloxacin, Sodomycin, Sufentanil, Sulpiride, Taclopramide, Talaposta, Tamoxifen, Taliquida, Technetium TC-99M Tetraphosphine, Tegaserod, Terbinafine, Terconazole, Tetracaine, Tetracycline, Thiophanolfentanil, Thiproprazole, Thioridazine, Tevothiazol, Somizole, Thionepril, Tigecycline, Tocainide, Topazol, Toremifen, Trifluoperazine, Trimebutine, Trimebutine Benzylamine, Triprine, Triptoridine, Tromethamine, Tubocurane, Udenafil, Varanoslin, Veripani, Venlafaxine, Viveverol, Verazorone, Veroxadone, Vincronidine, Vincristine, Vindesine, Vinorelbine, Laurylamine, Vortioxetine, Zaridroden, Zantinol, Zanapezil, Zotepine, Zincylthiasol, α-Methylfentanyl, α-Methylthiofentanyl, β-Hydroxythiofentanyl, or combinations thereof.

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

40. The pharmaceutical composition of claim 39, wherein the pharmaceutical compound comprises 1-benzopyran, 1-benzothiaran, 1-hydroxy-4-unsubstituted benzene compounds, 4-quinoline methanol, 5'-deoxy-5'-thionucleoside, amine, amino acid, peptide, aminophenyl ether, aminoquinoline, acetanilide, anisole, anthraquinone, hydroquinone, benzenesulfonamide, benzo-1,4-dioxane, benzodiazepine, benzoic acid, benzyl nitrile, benzoquinoline, benzoxazinone, benzoyl, benzyl alcohol, benzyl ether, benzylpiperidine, β-lactam, biphenyl, bisphosphonates, carbazole, carbohydrates and carbohydrate conjugates, indigo, phenolic peptides, dibenzodiazepines, dibenzothiocyanates, dibenzooxazines, dicarboxylic acids, diphenylacetonitrile, diphenylmethane, diterpenoids. Compounds, ethers, fentanyl, glycerophosphoserine, halobenzenes, heteropeptides, hydrogenated pyridine, hydrogenated quinoline, hydroxypyridine, indazole, indole carboxylic acid, indole, indoline, indoroquinoline, indole carboxylic acid, isoquinoline quinone, lysergic acid, methoxybenzene, naphthidine, nitrobenzene, nitroquinoline, organic sulfonic acids, pentacarboxylic acids, phenethylamine, fenilam, phenothiazine, phenoxazine, phenoxy compounds, phenoxyacetic acid, phenylacetamide, phenylbutylamine, benzylamine, phenylpiperidine, phenylpropane, phenylhyoscyamine, piperazine, piperidine carboxylic acid, pregnane steroids, purines and purines, pyridinium, quinoline carboxylic acid, quinolones, steroid esters, styrene, substituted pyrroles, sulfonylaniline, tametriline, thiophene carboxylic acid, toluene, trifluoromethylbenzene, tryptamine, tyrosol or derivatives thereof or combinations thereof.

41. The pharmaceutical composition of claim 39 or 40, wherein the pharmaceutical compound comprises (3S)-3-methyl-D-aspartic acid, isocortin, 13-deoxydoxorubicin, 3-allyl fentanyl, 3-methylfentanyl, 4-phenylfentanyl, 7-hydroxyspicoline, acebutolol, S-adenosylmethionine, adoloxin, alendronate, aliximazine, aliskiren, amotriptan, alogliptin, alprazolam, ambroxol, amibelonone, amikacin, amigonic acid, aminocontin, amitriptyline, amlodipine, and bismuth subcitrate. Amphetamine B, Atazoline, Apramycin, Apralindine, Abaclofen, Abexocin, Abutamine, Afortrol, Arelolomo, Aprolol, Arylacetamide, Atenolol, Atoxitin, Atoxiban, Atropine, Azithromycin, Bacitracin, Baclofen, Babutrol, Badoxifene, Betcalin, Benflurex, Benzatropine, Benzylphenamine, Benzylpenicillin, Thiazolyl-Lysine, Betastin, Bepridil, Besifloxacin, Betahistine, Betahistine, Betahistine, Betahistine, Betahistine, Bilastine, Clopidogrel, Biperidone, Bisoprolol Porfenolol, Butofenol, Bromhexine, Bromdapoxetine, Brompheniramine, Butifrolol, Blavallorol, Butenafine, Cabergoline, Canphosphatamide, Carbocysteine, Carteolol, Caspofungin, Sildenafil, Cefalexin, Cefoloza, Celiprolol, Chlorpheniramine, Chlorpromazine, Chlorprothiazide, Cilastatin, Cincocaine, Cialis, Citalopram, Clomastine, Clenbuterol, Chlorcarmine, Clofazimine, Clomiphene, Clomipramine, Cobitinib, Codeine, Colestipol, CP-122721, Cymemazine, Cyclobenzaline, Cyclobenzone Cystine, Indigoferazone, Dapavancin, Dapoxetine, Dapoxetine, Dalinpacin, Desclopramide, Demetriline, Desloratadine, Dextromethorphan, Dextromethorphan Maleate, Dextromethorphan, Dextromethorphan, Dextropropoxyphene, Dextrothyroxine, Dezocine, Diphenoxyphene, Dihydrocodeine, Metformin, Metformin, Diphenidol, Dipiformin, Diprenorphine, Dierythromycin, D-methionine, Dobutamine, Dopamine, Doripenem, Duthipine, Doxepin, Dronedarone, Duloxetine, Encani, Enclomiphene, Ephedrine, EpiceptNP-1, Eribulin, Ertapenem, Etapril, Esmolol, Ethambutol, Profenamide, Ethylmorphine, Eticacaine, Ethyltryptamine, Fennoterol, Fensipride, Ferrous Glycine, Fexofenadine, Flannib, Fingolimod, Flucainide, Fluoxetine, Fluspiline, Fluvoxamine, Formoterol, Freund's Mycelium, Gabapentin, Gadobacterium, Gadolinium Trisodium, Gadolinium Dimeglumine, Gadolinol, Gadoxetine, Gemmifloxacin, Glutamic Acid, Glutathione, Glutathione Disulfide, Glycine, Golomod, Gorgliptin, Granisetron, Haloferone, Heroin, Hecticine, Heccaine, Histamine, Histidine, Homatropine Huperzine A, Huperzine B, Hydroxybufenazole, Hydroxychloroquine, Hyoscyamine, Ibandronate, Efenidil, Imipramine, Indacaterol, Ioflupane I-123, Irinotecan, Iotaline, Isopin, Ivabradine, K201, Kanamycin, Labetalol, L-Alanine, L-Aspartate, L-Citrile, L-Cysteine, L-Lercanidipine, Leukotriene C4, Levofloxacin, Levoamlodipine, Levobetalol, Levobuprofen, Levodopa, Levomethadone, Levomilnacipran, Levofenoxate, Levothyroxine, L-Glutamine, Linagliptin, Iothrolone, Compound Thyroxine, L-Isoleucine, LJP1082, L-Leucine, Lometrexed, Loperamide, L-Phenylanine, L-Threonine, L-Tryptophan, L-Tyrosine, Benfluorenol, L-Valine, Lysylcycline, Sulfamethoxazole, Magnesium Glycine, Mefloxacin, Melphalan, Meropenem, Metarhamnol, Methadone, Acetatemethadone, Methionine, Levomethazine, Metoxamine, Methyldopa, Methylphenidate, Methemolol, Methoxane, Metoclopramide, Metoprolol, Methyltyrosine, Mexiletine, Mibeprazole, Milnacipran, Mirabelon, Mitansinol, Mitoxantrone, MN-305, Morphine, Moxifloxacin, Nadolol, Naftifine, Namefen, Naratriptan, Naronapride, Natal Mycin, Nemonoxacin, Netilmicin, Nitroarginine, NPS-2143, NS-2359, Nystatin, Oglufanine, Odanoterol, Olopatadine, Homoharringtonine, OPC-28326, Osinarine, Osanetin, Oseltamivir, Oxaniquine, Olofolin, Serotonin, Oxenolol, Pamidronate, Paroxetine, Paroxetine, Penicillamine, Pentoxyverine, Pergolitide, Phenylephrine, Indoleamine, Feniramine, Phentolamine, Phenylephrine, Phenylephrine, Pholcodine, Phosphatidylserine, Piperazine, Indoleolol, Piperazine, Pirarubicin, Pirbuterol, Pifenamic acid, Zinc prasinose, Pracinositol Pramolol, Procainamide, Procaterol, Procycline, Promethazine, Promirtine, Propafenone, Propoxyfen Naphthylsulfamate, Propranolol, PRX-03140, Pseudoephedrine, PX-478, Quarfloxin, Quinidine, Quinidine Barbiturate, Quinine, Repinovantan, Retaparin, Ribomycin, Ritodrine, Rizatriptan, Ronacarb, Roxithromycin, Salbutamol, Salmeterol, Sarredutan, Selenomethionine, Seroxetine, Sertraline, Sibutramine, Silodosin, Cilamecone, Sorabelon, Sotalol, Spectinomycin, Spiramycin, Sumatriptan, Sunitinib, Tamsulosin, Tandutinib Tapendarone, TAS-108, Taurine, Tedesamine, Terbutaline, Terfenadine, Telmilipin, Tersofencin, Tetrodotoxin, TG-100801, Tigaben, Ticapride, Tilmicosin, Timolol, Tobramycin, Topotecan, Tramadol, Transphenylcyclopropamine, Triethylenetetramine, Trifluoropromethazine, Trihexyphenidyl, Trimetazidine, Trimipramine, Travafloxacin, Tyramine, Ubenimex, Vancomycin, Vandetanil, Vareniclan, Vecuronium bromide, Verapamil, Vernacalan, Vigabatrin, Vilanterol, Vildagliptin, Zolmitriptan, α-Methylacetylfentanyl, α-Methylfentanyl, β-Methylfentanyl or combinations thereof.

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

43. The pharmaceutical composition of claim 42, wherein the pharmaceutical compound comprises 2,6-dimethyl-3-benzo[a]arene, alkaline earth metal oxides, alkyl thiols, amines, amino acids, peptides, aminopyridine, aminoquinoline, hydroquinone, benzoic acid, benzo[a]quinoline, β-lactam, cholic acid, alcohols, biphenyl, bisphosphonates, carbazole, carbohydrates and carbohydrate conjugates, carboxylic acid derivatives, cyclohexylamine, phenolic peptides, dibenzo[a]azine, diphenylmethane, ethers, fatty acids and conjugates, guanidine, halobenzenes, heteropeptides, indole carboxylic acids, indole, indoline, monoterpenoids, n-arylamides, organic sulfonic acids, peptide-peptide hybrids, phenethylamine, fenilam, phenylbutylamine, benzylamine, phenylpiperidine, phenylpropane, phenylpropylamine, phenylpyridine, piperidine carboxylic acid, purines and purine derivatives, pyrazolylpyridine, pyrimidines and pyrimidine derivatives, tetracarboxylic acids, tryptamine, urea, xylene or its derivatives or combinations thereof.

44. The pharmaceutical composition of claim 42 or 43, wherein the pharmaceutical compound comprises 2-iminobiotin, abaricicliz, ABT-510, afanotoxin, guanidine, acetaminophen, avimopanol, amantadine, AMD-070, amifostine, aminocaproic acid, amodiaquine, amphetamine, anatibant, apomorphine, argatroban, avirapamil, atemod, adipidil, bedoradine, benzodiazepine, betanidine, bisifafine, bivalirudin, brotamethasone, buprenorphine, butorphanol, butiline, capreomycin, urea peroxide, cefotaxime, ceritinib, cetrorecliz, chlorhexidine, chloroquine, chlorpheniramine, cinacalcet, trifluoroacetic acid, cortisone, Cr665, creatine, crizotinib, cysteine, CZEN002, Davapril, Dafenadine, Isoquinoline, Deferoxamine, Degarelix, Decaseline, Denibulin, Desipramine, Dilorelin, Desmopressin, Dexfenfluramine, Dextromethorphan, Diethylseminated succinate, Dihydrostreptomycin, Diisoproterenol, Eflunomide, Envelopromycin, Etorphine, Benzovasopressin, Fencanfamin, Fenethine, Fenfluramine, Fenodopan, Fexordil, Furazolidone, Furotriptan, Thiamine, Gadolin, Gadolinol, Gamma-aminobutyric acid, Ganirelin, Gentamicin, Gonaraline, Goserelin, Guanazor, Guanethidine, Guanidine, Halofanthracetam, Hesonaline, Histaminerelin, Hydroxyproline, Hydroxyethyl Hydroxystilbene sulfonate, Ibutilide, Itiband, Imipenem, Indapine, Indicarbide, Iodobenzylguanidine, Iodobenzylguanidine sulfate I-123, Imometidine, Labedimir, L-aminocarnitine-succinyl-leucyl-arginine aldehyde-diethyl acetal, Lanrethide, L-arginine, L-ornithine, Levodeoxyephedrine, Levocarbastine, Lysine amphetamine, Lisinopril, Lixifenatide, L-lysine, Lorcaserin, L-proline, Magnesium oxide, Maprotiline, Maraviro, Mecaramine, Memantine, Mefenamic acid, Metformin, Metformin, Midomafelamine, Nafarelin, Nabuphine, Naltrexone, Naphazoline, Nelamesin Neridonine, Nintedanib, Nor-noha, Nortriptyline, Benzylpropionate, Onipetide, Octreotide, Olcegepant, Ornithine, Omisaban, Oxymethasone, Omexaban, Oxymethoxazole, Papirostat, Pacilostide, Pemetrexed, Pentamivir, Pentazocine, Peramivir, Piperacillin, Phenylephrine, Phentermine, Pimagateline, Piracetam, Presalifos, Polymyxin B Sulfate, Pozaniclone, Pramipexole, Pregabalin, Prezatide, Primaquine, Flusalamide, Chlorguanidine, Propyltriamine, Protriptyline, Tiamethoxazole, Quinacrine, Remolanine, Rifaximin, Amantadine, Rivanol Lin, Romidesin, Ropinirole, Rotigotine, Salazine, Saplatin, Serotonin, SGS-742, Sitamalaquine, SNS-032, Somatostatin, Spermine, SQ-109, Squalamine, Streptomycin, T131, Tafenoxanil, Tarlotrexine, Tanspiramycin, Ticasmazole, Tenocron, Terlipressin, Temorelin, Tecoctocin, Tetrahydrozoline, Tezappanone, Tipiridine, Tirofiban, Tolazoline, Tolterodine, Taurine, Triptorelin, Uralidide, Urea C-13, Vapirtidine, Vintafolide, Vitismycin, WX-UK1, Xylometazoline, Zanamivir or combinations thereof.

45. The pharmaceutical composition according to any one of claims 1-44, wherein the pharmaceutical composition is a solid.

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

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

5.

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

49. The pharmaceutical composition of claim 45, wherein the pKa of the pharmaceutical compound is from 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 pKa of the pharmaceutical compound is at least 5.

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

53. The pharmaceutical composition according to any one of claims 1-52, wherein the pharmaceutical composition, when formulated as a solution, has a weight osmotic molar concentration lower than that of a solution of the composition comprising a salt containing the pharmaceutical compound and a salt containing the complexing agent.

54. The pharmaceutical composition of any one of claims 1-53, wherein, compared with a composition that does not contain the complexing agent or (ii) wherein the pharmaceutical compound does not complex with one or more of the acidic functional groups of the complexing agent, the pharmaceutical composition improves the 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%.

55. The pharmaceutical composition of any one of claims 1-54, wherein, compared to a composition that does not contain the complexing agent or (ii) wherein the pharmaceutical compound does not complex with one or more of the acidic functional groups of the complexing agent, the pharmaceutical composition improves the solubility of the pharmaceutical compound by about 2 times, about 3 times, about 4 times, about 5 times, about 6 times, about 7 times, about 8 times, about 9 times, about 10 times, about 20 times, about 30 times, about 40 times, or about 50 times.

56. The pharmaceutical composition of any one of claims 1-55, wherein the complexing agent comprises a substituted cyclodextrin.

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 sulfobutyl ether-β-cyclodextrin (SBEBCD).

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

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

62. The pharmaceutical composition of claim 1, wherein when formulated as a solution, the weight osmolar concentration of the pharmaceutical composition does not exceed about 850 mOsm / kg.

63. The pharmaceutical composition of claim 62, wherein the pH of the pharmaceutical composition is from 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 a counterion of 1 to 10 molecules of the pharmaceutical compound.

66. The pharmaceutical composition of claim 1, wherein the complexing agent further comprises a nonpolar 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 with the nonpolar pore.

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

1.

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

2.

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

3.

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

4.

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

5.

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

5.

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

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

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

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

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

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, copanlixetine, levodopa, tigecycline, naloxone, amikacin, 1-amantadine, 2-amantadine, rimantadine, amipridine, rapamycin, clonidine, morphine, hydrocodone, sumatriptan, ropivacaine, bupivacaine, diphenhydramine, granisetron, dechlorin, 2-fluoro-dechlorin, or caspofungin.

81. The pharmaceutical composition according to any one of claims 1-80, wherein the pharmaceutical compound comprises a GABAergic agent.

82. The pharmaceutical composition of claim 81, wherein the GABAergic agent comprises baclofen, gapository, or muscarinic acid, or a combination thereof.

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

84. The pharmaceutical composition of claim 83, wherein the α-2 agonist comprises clonidine, guanfasin, or tizanidine, or a combination thereof.

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

86. The pharmaceutical composition of claim 85, wherein the ophthalmic agent comprises acetylcholine, atropine, azelastine, bromonidin, cyclopentolate, ketotifen, levobunolol, olopatadine, spirocarpine, promecaine, tetracaine, timolol, or tropicamide.

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 thereof, or two or more thereof.

89. The pharmaceutical composition according to 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, ceftoran, cefepime, cefdil, cefixime, cefmetazole, cefoperazone, cefotaxime, cefotetan, cefotaxime, cefoxitin, cefpodoxime, cefprozil, cefalorline, ceftazidime, cefbufen, cefazolin, cefuroxime, cefoloza, ceftriaxone, cefuroxime, cefalexin, cefepime, cefepime, cefradine, ciprofloxacin, clarithromycin, cloquinolones, colistin, dapavancin, Dalfopristin, daptomycin, doripenum, doxycycline, ertapenem, eracycline, erythromycin, fosfomycin, gentamicin, imipenem, kanamycin, lefamolin, levofloxacin, linezolid, lincomycin, meropenem, metronidazole, minocycline, moxifloxacin, nalidixic acid, neomycin, nitrofurantoin, orivoxil, penicillin, piperacillin, polymyxin B, quinupristin, retaparin, rifampin, streptomycin, sulfacetamide, sulfadiazine, sulfamethoxazole, sulfasalazine, sulfasalazine, sulfisoxazole, teicoplanin, tervacancin, tetracycline, tigecycline, tobramycin, trimethoprim, or vancomycin or combinations thereof.

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

92. The pharmaceutical composition of claim 91, wherein the anticoagulant or thrombolytic agent comprises alteplase, argatroban, bivalirudin, fondaparinux sodium, lepirudine, streptokinase or urokinase, or combinations thereof or two or more thereof.

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

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

95. The pharmaceutical composition of claim 93, wherein the antifungal agent comprises albendazole, clotrimazole, econazole, fluconazole, isaconazole, itraconazole, ketoconazole, miconazole, posaconazole, tebuconazole, thiabendazole, or voriconazole, or combinations thereof, or two or more thereof.

96. The pharmaceutical composition of claim 93, wherein the antifungal agent is amphotericin B, anisofungin, caspofungin, flucytosine, micafungin, natamycin, or voriconazole, or a combination thereof, or two or more thereof.

97. The pharmaceutical composition according to any one of claims 1-80, wherein the pharmaceutical compound is an antitumor drug.

98. The pharmaceutical composition of claim 97, wherein the antitumor drug is afatinib, alectinib, arisetinib, axitinib, bosutinib, cabozantinib, cannetinib, carfilzomib, siddinib, ceritinib, cimetidine, cobitinib, dabrafenib, darazabine, dasatinib, decarsetinib, dovitinib, erlotinib, etorcoxib, felanib, gresartinib, ibrutinib, ederalipix, imatinib, ispinib, ixazomib, lapatinib, lenvatinib. Nitroglycerin, lincitinib, lonafab, masatitinib, motisanib, nilotinib, nintedanib, odandarbitril, olaparib, onanacipiride, osimertinib, palbociclib, pazopanib, peritrinib, ponatinib, regorafenib, renalapadi, ruxolitinib, celicil, sorafenib, sunitinib, tandutinib, tepififib, tofacitinib, vandetanib, varitinib, varitinib, vatalani, veripabinib, vemurafenib, vemodegil, or combinations thereof or two or more thereof.

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

100. The pharmaceutical composition of claim 99, wherein the antiviral agent comprises abacavir, acyclovir, adefovir, amantadine, ampravir, atazanavir, bicretiravir, cidofovir, darunavir, dasabuvir, deraviridine, norinosine, dolutegravir, efavirenz, erteiravir, emtricitabine, enfuvirtide, entecavir, famciclovir, foscarnet, ganciclovir, grazoprevir, imiquimod, indiravir. Lamivudine, Lanimivir, Leadipasvir, Lopinavir, Maraviro, Nafinavir, Nevirapine, Obitasvir, Oseltamivir, Palirivir, Penciclovir, Peramivir, Prexafovir, Podophyllotoxin, Raltegravir, Ribavirin, Rilpivirin, Ritonavir, Saquinavir, Sofosbuvir, Stavudine, Tenofovir, Telanavir, Trifluridine, Valacyclovir, Valganciclovir, Zanamivir, or Zidovudine or combinations thereof.

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

102. The pharmaceutical composition of claim 101, wherein the cardiovascular drug comprises bromide, dobutamine, dopexamine, eprostol, esmolol, iloprost, nesiritide, nitroglycerin, norepinephrine or phenylephrine, or combinations thereof 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, nitrazepam, clonazepam, diazepam, dexmedetomidine, dextromethorphan, flurazepam, gabapentin, ketamine, lorazepam, midazolam, oxazepam, propofol, temazepam, or triazolam, or combinations thereof, 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, dextromethorphan, dextromethorphan, ephedrine, lysine amphetamine, methylphenidate, methylphenidate, modafinil, phenylephrine, pseudoephedrine, or sibutramine, or combinations thereof, 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, dibutylcaine, eticaine, levobupivacaine, lidocaine, malbivocaine, prilocaine, procaine, prilocaine, ropivacaine, or tetracaine, or combinations thereof.

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

110. The pharmaceutical composition of claim 109, wherein the antiemetic 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 drug.

112. The pharmaceutical composition of claim 111, wherein the anti-migraine drug comprises amotriptan, avetriptan, doniptriptan, eletriptan, frotriptan, lamitantan, nalatriptan, 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 disease drug.

114. The pharmaceutical composition of claim 113, wherein the anti-Parkinson's disease drug comprises amantadine, apomorphine, benzalkonium chloride, benserazide, bromocriptine, cabergoline, carbidopa, entacapone, foscarbidopa, foscarbidopa, levodopa, melevopa, pramipexole, rasagiline, ropinirole, rotigotine, safenamide, selegiline, tocapone, or trihexyphenidyl or combinations 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 avastin, brompheniramine, cetirizine, chlorpheniramine, chlormastine, cyproheptadine, desloratadine, dextrochlorpheniramine, diphenhydramine, doxylamine, fexofenadine, hydroxyzine, levocetirizine, loratadine, meclopramide, promirtine, or tropineamine, or combinations 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 substance.

120. The pharmaceutical composition of claim 119, wherein the opioid substance comprises buprenorphine, butorphanol, codeine, fentanyl, heroin, hydrocodone, hydromorphone, levonorphine, pethidine, methadone, morphine, naloxone, naltrexone, nalmefenamic acid, oxycodone, oxymorphone, pentazocine, sufentanil, tapentadone, or tramadol, or combinations thereof, 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 amipyridine, amifostine, aminocaproic acid, argatroban, asenapine, atropine, bivalirudin, cisatracurium, deferoxamine, desmopressin, gabapentin, lurasidone, milrinone, nicotine, octreotide, pregabalin, rocuronium bromide, terbutaline, tirofiban, tranexamic acid, vecuronium bromide, naprafenamide, or any combination thereof.

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

10.

125. A pharmaceutically acceptable salt of a compound drug, comprising: (i) a pharmaceutical compound or its enantiomers, mixtures of enantiomers or isotopic variants; or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the pharmaceutical compound comprises a protonated nitrogen atom and has a pKa of at least 1; as well as (ii) A conjugate base of a complexing agent comprising a plurality of acidic functional groups, wherein at least one 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 about 1:1 to about 1:

10.

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

10.

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

10.

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

129. A pharmaceutically acceptable salt according to any one of claims 124-128, wherein the complexing 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 sulfobutyl ether-β-cyclodextrin (SBEBCD).

132. The pharmaceutically acceptable salt of any one of claims 124-131, wherein the pKa of the pharmaceutical compound is at least 1.

133. The pharmaceutically acceptable salt of any one of claims 124-132, wherein the pKa of the pharmaceutical compound is from about 1 to about 7.

5.

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

135. The pharmaceutically acceptable salt of any one of claims 124-134, wherein the pKa of the pharmaceutical compound is about 7.5 to about 13.

136. A pharmaceutically acceptable salt according to any one of claims 124-135, wherein the pharmaceutical compound comprises 5'-deoxyribonucleoside, 6,7-benzomorphine, amaryl-snake root alkaloid, alkaline earth metal organometallic compounds, amaryllidaceae alkaloids, anthracene, anthracene rings, apophene, azaspirodecane, azacycloheptane, azobenzene, azole, azoleidine, azoleline, benzo[a]azonium, benzene and substituted benzene, benzimidazole ribonucleoside and ribonucleotide, benzimidazole, benzo[a]cycloheptylpyridine, benzo[a]diazazepine, benzo[a]dioxane, benzo[a]dioxane, benzo[a]dioxane, benzo[a]furan, benzo[a]pyran, benzo[a]pyrazole, benzo[a]thiadiazole, benzo[a]thiazole, Benzothiazine, benzothiazolium, benzothiocyanate, benzothiophene, benzothiaran, benzotriazole, benzoxadiazole, benzooxazine, benzoxazine, benzooxazine, biotin, camptothecin, carboxylic acid, Cephalotaxus alkaloids, cinchona alkaloids, cinnamic acid, coumaranthium, cycloheptaphene, condensed phenolic acids and condensed phenolic acid cyclic ethers, diarylheptane compounds, diazanaphthalene, diazacyclohexane, diazine, dibenzocycloheptenene, dioxane, epoxides, ergoline, fatty acyl groups, flavonoid nucleotides, flavonoids, fluorene, furan, furanopyran, glycerophospholipids, other homogeneous nonmetallic compounds, hydroxy acids, ibogan-type alkaloids, imidazodiaza, imidazodiaza Azoxyribonucleosides and ribonucleotides, imidazopyridine, imidazopyrimidine, imidazothiazole, indene, indene and isindene, indole, indolizidine, isocoumaranth, isoindole, isoquinoline, lactam, linear 1,3-diarylpropane, lupin alkaloids, macrolactams, macrolide lactams, macrolide morphine, tetraphenyl, naphthalene, naphthofuran, naphthopyran, nucleoside and nucleotide analogs, organic carbonic acid, organophosphorus, organophosphonic acid, organic sulfonic acid, organic nitrogen compounds, organic oxygen compounds, organic thiophosphorus compounds, oxazine, peptide analogs, phenanthrene, phenanthroxolin, phenol esters, phenol ethers, phenol, phenylpropionic acid, phthaloylisoquinoline, piperazine-azohydrazine, Piperidine, polypeptides, isopentenol lipids, pteridine, purine nucleosides, purine nucleotides, pyrazolopyridine, pyrazolopyrimidine, pyridine, pyridopyrimidine, pyrimidine nucleosides, pyrrole, pyrrolidine, pyrrolopyrazine, pyrrolopyridine, pyrrolopyrimidine, quinoline, steroids and steroids, piracetam, tetracycline, tetrahydroisoquinoline, naphthiazine, thienodiazazine, thienopyridine, thienothiazine, thiochromene, thioethers, thiols, thiophene, transition metal salts, triazacyclohexane, triazine, triazole ribonucleosides and ribonucleotides, triazole pyrimidine, triphenyl compounds, hyoscyamine alkaloids, vinca alkaloids, yohimbine alkaloids or their derivatives or combinations thereof.

137. The pharmaceutically acceptable salt of any one of claims 124-134, wherein the pKa of the pharmaceutical compound is about 1 to about 2.

138. The pharmaceutically acceptable salt of claim 137, wherein the pharmaceutical compound comprises 1,4-benzodiazepine, amine, amino acid, peptide, androstened steroid, benzenesulfonamide, benzoic acid, benzophenone, benzothiadiazine, biphenyl, carboxylic acid derivative, phenolic peptide, diphenylmethane, ether, halobenzene, isoindoline, nitrogen mustard compound, nitroquinoline, purine 2'-deoxyribonucleoside, purine, pyrazole, pyrimidine or derivative thereof, retinoid, substituted pyrrole or combinations thereof.

139. The pharmaceutically acceptable salt of claim 138, wherein the pharmaceutical compound comprises apatideson, asunaprevir, azilsartan medoxomil, benzylthiazide, bromfenac, candesartan medoxomil, epinephrine, chlorambucil, chlorothiazide, cladribine, clofarabine, clonazepam, CVT-6883, CX516, dacarbazine, diazoxide, ammodendron, femasartan, flubendazole, flucytosine, fludiazepam, flunitrazepam, ganciclovir, gliclazide, glimepiride, grapravir, guanosine, isobutylsitol Terbuprofen, Isobutyric acid, Iopamidol, Iopamidol, Isobutyric acid, Isatoribine, Ixazomib, MB-07803, Nateglinide, Nepafenamide, OPC-51803, Praconazole, Pomalidomide, Punicarboxyfen, Pyrantel, Regadesone, Rimonaban, Selepag, Smepiride, Sulfamethoxypyrimidine, Sulfamethoxypyrimidine, Sulfamethadiazole, Sulfamethoxazole, Sulfamethin, Sulfamethoxazole, Tarenaban, Tazarotene, Thiopronine, Tolazoline, Trapidil, Uracil nitrogen mustard, or combinations thereof.

140. The pharmaceutically acceptable salt of any one of claims 124-134, wherein the pKa of the pharmaceutical compound is about 2 to about 3.

141. The pharmaceutically acceptable salt of claim 140, wherein the pharmaceutical compound comprises azobenzene, azole, benzodiazepine, benzene, benzodiazepine, benzothiazine, benzothiazolium, carboxylic acid, phenolic acid, diazonium, diazine, imidazopyrimidine, indole, isoindole, lactam, macrolide naphthalene, nucleoside and nucleotide analog, organic oxygen compound, piperidine, isopentenyl alcohol lipid, pteridine, purine nucleoside, purine nucleotide, pyrazolopyrimidine, pyridine, pyrimidine nucleoside, pyrrolopyridine, quinoline, steroid, thienodiazepine, triazine, triazolopyrimidine or combinations thereof.

142. The pharmaceutically acceptable salt of claim 141, wherein the pharmaceutical compound comprises 1,4-benzodiazepine, amino acid, peptide, aminotriazine, androstened steroid, sulfaniline, aniline, benzodiazepine, benzenesulfonamide, benzenesulfonyl compound, benzodiazepine, benzoic acid, β-lactam, biphenyl, carbazole, diphenyl ether, diphenylmethane, epothilone estradiol, ether, halobenzene, isoindoline, milbemycin, monoterpenoid, nitroquinoline, oxosteroid, phenoxyacetic acid derivative, phenylbutylamine, phenylcarbamate, benzylamine, phenylpropane, phenylquinoline, pterin, purine 2',3'-dideoxyribonucleoside, purine ribonucleotide, purine and purine derivative, pyrazole, pyrazolo[3,4-d]pyrimidine, pyridinecarboxylic acid, pyrimidine and pyrimidine derivative, sulfaniline, or combinations thereof.

143. The pharmaceutically acceptable salt of claim 141 or 142, wherein the pharmaceutical compound comprises acyclovir, adecidyllon, allistois, allopurinol, ambrisentan, amerubent, aminobenzoic acid, aminopterin, aminosalicylic acid, ampravir, anastrozole, para-aminobenzoic acid, asoprilinide, benzocaine, BMS-488043, becanavir, bromazepam, buprofen. Metformin, Butanben, Cangrelox, Cefixime, Cefpirome, Chromium pyridinecarboxylate, Sidofovir, Sirupvir, Cinasteride, Clarsentan, Clotrazepam, Chloroxazolam, Dabrafenib, Dapsone, Darunavir, Diloxacin, Diazepam, Doxorubicin, Dutasteride, Edonotecan, Efodipine, Ecirapine, Entecavir, Epilazole, Epothilone D, Finasteride, Fluconazole, Flumetazidine ( 18 F), Folic acid, metoprolol, fosanavir, ganstigmine, GW-501516, halazepam, indocyanine green, inosine, iodamide, iopromide, essaconazole, ixaspirin, KOS-1584, KP-1461, lenalidomide, letrozole, folinic acid, levofolinic acid, macitentan, meladidone, mercaptopurine, methotrexate, methylene blue, methylthionine, motexafen gadolinium, motexafen luteolin, moxifloxacin, naciline, nitrazepam, nitrohydroxyquinoline, olaparib, olbitahim, OT-551, pardimethicone O, pariprevir, parupilone, penciclovir, aminosalicylic acid phenyl ester PPL-100, pralatrexate, quazepam, rivconazole, regorafenib, regreroline, ritonavir, roflumilast, roxadustat, silver sulfadiazine, sorafenib, stanozolol, sulfabenzoyl, sulfacetyl, sulfaxitin, sulfadiazine, sulfadoxine, sulfamethazine, sulfadiazine, sulfamethazine, sulfabenzopyrazole, sulfapyridine, sulfasalazine, sulfathiazole, sulfisoxazole, tannetan, tasosartan, technetium[99mTc]desofenine, technetium[99mTc]methylbromofenmin, tezosentan, ticagrelor, terazamine, trisatabine, trypan blue, voriconazole or combinations thereof.

144. The pharmaceutically acceptable salt of any one of claims 124-134, wherein the pKa of the pharmaceutical compound is about 3 to about 4.

145. The pharmaceutically acceptable salt of claim 144, wherein the pharmaceutical compound comprises 1,4-benzodiazepine, amino acids, peptides, acetanilides, anilines and substituted anilines, anisoles, aryl sulfides, benzodiazepines, benzofuranones, benzoic acid and derivatives, benzophenones, β-lactams, biphenyls and derivatives, bipyridines and oligopyridines, carbodiimides, diphenyl ethers, diphenylmethane, epothilone estradiols, ethers, Halogenated quinolines, hexacarboxylic acids and their derivatives, imidazoles, isoindole, milbemycin, morpholine, phenoxyacetic acid derivatives, benzylamine, phenylpyridine, piperazine, pterin and its derivatives, purine 2',3'-dideoxyribonucleoside, purines and their derivatives, purines and their derivatives, pyrazines, pyrazoles, pyridine carboxaldehyde, pyridine carboxylic acids and their derivatives, pyridine sulfonamides, pyridyltriazoles, steroid esters, sulfonylaniline, sulfinylbenzimidazole, or combinations thereof.

146. The pharmaceutically acceptable salt of claim 144 or 145, wherein the pharmaceutical compound comprises adenosine, amiloride, aminobenzoic acid, aminopyrine, anagrelide, aprepitant, para-aminobenzoic acid, azathioprine, aztreonam, benzocaine, benzonatate, diacetylbenzoic acid, bromazepam, bromotezolam, bumetanide, butanben, calcium cyanamide, cefepime, cefixime, cefotaxime, cefotaxime, cefpodoxime, cefazolin, ceftriaxone, chlorhexidine, chromium pyridinecarboxate, cloiodriquinone, dabigatran etexilate, dabrafenib, dexlansoprazole, dexrazoxen, diazepam, norinosine, diiodohydroxyquinoline, entecavir, etofibrate, itravirine, ezogabaline, flumazenil, flumetazidine ( 18 F), Indigo, Inosine, Nicotinic Acid Inositol Ester, Iophobic Acid, Irbesartan, Iscarbohydrazine, Isoniazid, Itraconazole, Ixaspirone, Lansoprazole, Leucovorin, Levofolinic Acid, Rosiglitazone, Losartan, Lumacartocin, Maindo, Mebendazole, Mercaptopurine, Mercaptopurine, Methotrexate, Metronidazole, Montelukast, Montelukast, Moxifloxacin, Nerapine, Nicotinic Acid, Nicotinamide, Norgestrel, Norgestrel, Olfendazole Padimamate, pantoprazole, penciclovir, perampanel, picosulfate, piroxicam, posaconazole, pralatrexate, pralatrexam, procaine ethoxymercurin, pyridoxal, pyridoxal phosphate, riociguat, ritonavir, stanozolol, tanidazole, tasosartan, tenofovir disoproxil fumarate, thiabendazole, tonazolium, ticagrelor, tinidazole, thioguanine, topiroxetine, torasemide, triamterene, triamterene, vemurafenib, vemurafenib, vemodilide, or combinations thereof.

147. The pharmaceutically acceptable salt of any one of claims 124-130, wherein the pKa of the pharmaceutical compound is about 4 to about 5.

148. The pharmaceutically acceptable salt of claim 147, wherein the pharmaceutical compound comprises 1,4-benzodiazepine, 1-ribosyl-imidazolium carbamate, 2-benzimidazolyl carbamate, 8-hydroxyquinoline, amine, amino acid, peptide, androstened steroid, acetanilide, aniline and substituted aniline, anthraquinone, aryl sulfide, benzodiazepine, benzoic acid and its derivatives, β-lactam, biphenyl and its derivatives, bipyridine, oligopyridine, bisphosphonates, carbonyl compounds Diphenylmethane, ethers, hexacarboxylic acids and their derivatives, imidazoles, imidazoquinolines, indolequinones, naphthidines, oxosteroids, phenethylamine, phenylbenzimidazole, phenylhydrazine, phenylpiperidine, phenylpyridine, phenylquinoline, pterin and its derivatives, purine ribonucleotides, purines and their derivatives, pyrazolo[1,5-a]pyrimidine, pyridine carboxylic acids and their derivatives, pyridine sulfonamides, pyridoindole, quinoline carboxylic acids, styrene, sulfinylbenzimidazole, trifluoromethylbenzene or combinations thereof.

149. The pharmaceutically acceptable salt of claim 147 or 148, wherein the pharmaceutical compound comprises azathioprine, abiraterone, acalcein, 5'-adenosine sulfate, adenosine monophosphate, AICA ribonucleotide, albendazole, amphetalil, aminoglutethimide, aminohippuric acid, amrinone, atazanavir, aztreonam, banoxane, pinenodipine, diacetylphenidate, carfilzomib, cefotaxime, cefepime, cefotaxime, cefotaxime, cefpodoxime, ceftazidime, cefbufen, cefazolin, ceftriaxone, coenzyme A, dexlansoprazole, ensolazole, erlotinib, emeprazole, estazolam, etomidate, etomidate, ethorcoxib, itravirin, feboraben, flavin adenine dinucleotide, flubetaban ( 18 F), flubetapyr ( 18 F), Gerdemycin, Gentian Violet, Hexocyram, Adelalipic Acid, Impetatae, Indium In-111 Oxyquinoline, Nicotinic Acid Inositol Ester, Iophobic Acid, Irbesartan, Lansoprazole, Levosimendan, Loratadine, Lornoxicam, Losartan, LX-2931, Methoxyamine, Metheprone, Mifepristone, Milrinone, Minoxidil, Nafidinic Acid, Nicotinic Acid, Osiprolone, Omeprazole, OSI-930, Oxyquinoline, Perampanel, Pilidisone, Picosulfate ... Vastatin, limonin, PX-12, pyridoxal, pyridoxal phosphate, rabeprazole, repaglinide, riquimod, retamycin, lidogre, riluzole, risedronate, linaglitone, rosofloxacin, S-8510, sapropterin, ticardisone, tenofovir disoproxil fumarate, tenoxicam, thiabendazole, torasemide, triazolam, tucistat, uristat, varitinib, valproinib, verteporfen, velurubin, vidarabine, velpatinam, vorapazol, or combinations thereof.

150. A pharmaceutically acceptable salt according to any one of claims 124-134, wherein the pKa of the pharmaceutical compound is about 5 to about 6.

151. The pharmaceutically acceptable salt of claim 150, wherein the pharmaceutical compound comprises 1,4-benzodiazepine, 1-ribosyl-imidazolium carbamate, 2-benzimidazolyl carbamate, 8-hydroxyquinoline, amine, amino acid, peptide, androstened steroid, acetanilide, aniline and substituted aniline, anthraquinone, aryl sulfide, benzodiazepine, benzoic acid, β-lactam, biphenyl, bipyridine and oligopyridine, bisphosphonate, diphenyl Methane, ether, hexacarboxylic acid, imidazole, imidazoquinoline, indolequinone, naphthidine, oxosteroids, phenethylamine, phenylbenzimidazole, phenylhydrazine, phenylpiperidine, phenylpyridine, phenylquinoline, pterin, purine ribonucleotides, purines and purine derivatives, pyrazolo[1,5-a]pyrimidine, pyridine carboxylic acid, pyridine sulfonamide, pyridoindole, quinoline carboxylic acid, styrene, sulfinylbenzimidazole, trifluoromethylbenzene or its derivatives or combinations thereof.

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-methyltetrahydrofolate, abacavir, adefovir dipivoxil, adenine, alprazolam, ALT-2074, amdoxovir, apimod, adenosine triphosphate, avanafil, axitinib, azledipine, benazepril, and benzimidazole. Bisifenzyl, Biricorda disitate, Brilliant Green, Cabozantinib, Capvirine, Carbidopa, Cefepime, Cirivastatin, Cialapril, Cisplatin, Clavidipine, Clonisin, Clopidogrel, Cocarboxylase, Dapivirine, Desalazine, Dolastron, Elbasvir, Enalapril, Ethionamide, Etenofoline, Ethefosine, Etozoline, Famciclovir, Felodipine, Fulofenone, Forminoben, Fosaspirantan, GTS-21 Hattacil, Imidacloprid, Imiquimod, Incadronate, Indebulin, Issupanblue, Iradipine, Kinetin, Lamotrigine, Leadipasvir, Lincitinib, Melanathan, Mesalazine, Urotropin, Moxipril, Mornifluoxetine, NADH, Nevirapine, Nifedipine, Nifluoxetine, Nimodipine, Nisodipine, Nifedipine, Olmesartan, Pazopanib, Pedesine, Perindopril, Phenylebhydrazine, Pyrapoplatin, Pinafenadil, Pioglitazone Pipercuronium bromide, Pradefovir mesylate, Prasugrel, Prolinestana, Procarbazine, Pyridoxine, Quinapril, Ramipril, Rilpivirine, Ropepofen, Ruxolitinib, Celicillin, Sildenafil, Sonicidazole, Ropril, Sipofen, Tapimod, Talivirine, Temopril, Temopofen, Tenofovir alafenamide, Thiamine, Qundopril, Topiramide, Velpatasvir, Cimetazidine, Zinc Pyridinecarboxate, Zolpidem, or combinations thereof.

153. The pharmaceutically acceptable salt of any one of claims 124-129, wherein the pKa of the pharmaceutical compound is about 6 to about 7.

154. The pharmaceutically acceptable salt of claim 153, wherein the pharmaceutical compound comprises 1,4-benzodiazepine, 1-ribosyl-imidazolium carbamate, 2-benzimidazolyl carbamate, 8-hydroxyquinoline, amine, amino acid, peptide, androstened steroid, acetanilide, aniline and substituted aniline, anthraquinone, aryl sulfide, benzodiazepine, benzoic acid, β-lactam, biphenyl, bipyridine and oligopyridine, bisphosphonate, carbonyl compound. Diphenylmethane, ether, hexacarboxylic acid, imidazole, imidazoquinoline, indolequinone, naphthidine, oxosteroids, phenethylamine, phenylbenzimidazole, phenylhydrazine, phenylpiperidine, phenylpyridine, phenylquinoline, pterin, purine ribonucleotides, purines and purine derivatives, pyrazolo[1,5-a]pyrimidine, pyridine carboxylic acid, pyridine sulfonamide, pyridoindole, quinoline carboxylic acid, styrene, sulfinylbenzimidazole, trifluoromethylbenzene or its derivatives or combinations thereof.

155. The pharmaceutically acceptable salt of claim 153 or 154, wherein the pharmaceutical compound comprises 2-amino-1-methyl-6-phenylimidozolo(4,5-b)pyridine, 5-methyltetrahydrofolate, abacavir, adefovir dipivoxil, adenine, alprazolam, ALT-2074, amdoxavir, apimod, avanafil, azoledipine, benazepril, benzimidazole, bisacodyl, pyricin Bicocortide, Brilliant Green, capvirline, carbidopa, cerivastatin, cisplatin, clovidipine, clonidine, clopidogrel, cocarboxylase, dapoxetine, deramani, desarazine, dolasetron, elbavirin, Enalapril, Etefosine, Etozoline, Famciclovir, Felodipine, Fulofenin, Forminoben, Fosapitan, GTS-21, Hetacillin, Imidacloprid, Imiquimod, Incadronic acid, Indebulin, Issubanlan, Iradipine, Kinetin, Lamotrigine, Leadipasvir, Melanathana, Mesalazine, Urotropine, Moxipril, Mornifluoxetine, Nevirapine, Nifedipine, Nifluoxetine, Nimodipine, Nisodipine, Nifedipine, Olmesartan, Pazopanib, Pedesine, Perindopril, Phenylezil, Pyrapirocin, Pinafenadil, Piaglitazone, Piperacillin, Piperacillin, Pipercuronium bromide, Pradefovir Mesylate, Prasugrel, Prinstat, Procarbazine, Pyridoxine, Quinapril Ramipril, Rilpivirine, Ropepoxetine, Ruxolitinib, Celicillin, Sildenafil, Sonicidazole, Ropril, Sipofen, Tapimod, Talivirine, Temopril, Temopoxetine, Tenofovir Acetonide, Thiamine, Qundopril, Topicamid, Velpatasvir, Cimetazidine, Zinc Pyridinecarboxate, Zolpidem, Acarbose, Amaryl, Acaratadine, Alfentanil, Alfuzosin, Amitriazine, Amisulpride, Amoxicillin, Ampicillin, Amrubicin, Triprofen, Aripiprazole, Asenapine, Atemexazole, Azapiridone, Bambucillin, Cefaclor, Cefadroxil, Cefdinir, Cefprozil, Cefalexin, Cefalexin, Librium, Chlorpyrifos Tadalafil, dalfopritin, dasatinib, diethylamine benzophenone, domperidone, dazolidin, doxapram, doxazosin, drotavirine, iriconazole, ipramone, flavoxetine, flubancerine, flupiridine, midazoline, indinavir, ketamine, ketotifen, lapatinib, loxapine, mabifocaine, methacycline, mosonidin, nefazodone, olanzapine, ondansetron, benzotriazine, pimozide, promocaine, prazosin, quetiapine, ranolazine, rupatadine, septoprolol, terazosin, buphenazine, ticlopidine, tizanidine, tofacitinib, trazodone, trimethoprim, valacyclovir, valganciclovir, ziprasidone, or combinations thereof.

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

157. The pharmaceutically acceptable salt of claim 156, wherein the pharmaceutical compound comprises amaryl-snake root alkaloid, 1,4-benzodiazepine, 2,3,5-trisubstituted thiophene, alcohols and polyols, amines, amino acids or peptides, acetoaniline, anisole, benzodiazepine, benzo[a]arene, benzene, benzimazole, benzocycloheptapyridine, benzodiazepine, benzodiazepine, benzodiazine, benzofuran, benzoic acid, benzo[a]thiazide Zazole, benzothiazide, benzotriazole, benzooxyzide, benzooxyzide, benzylamine, benzylisoquinoline, benzylpiperidine, β-lactam, biphenyl, carbazole, carbohydrates, carbonyl compounds, carboxylic acids, cycloheptaphene, diarylheptane compounds, diazanaphthalene, diazacyclohexane, diazine, dibenzocycloheptene, dibenzodiazepine, dibenzothiazide, dibenzooxyzide, dibenzooxyzide, diphenylmethane, ergoline Flavonoids, flavonoids, halogenated benzenes, heteropeptides, hydrogenated pyridine, indene, indole, indoline, isoquinoline, isoquinoline ketones, lactams, linear diarylheptane compounds, lysergic acid, macrolactams, macrolide lactams, monoterpenoids, morpholine, n-acylpiperidine, n-alkylindole, tetraphenyl, naphthopyranone, naphthopyran, n-phenylurea, organic nitrogen compounds, organic oxygen compounds, oxazine, pentacarboxylic acids, peptide mimics, phenanthrene Phenethylamine, phenol ether, benzylamine, phenylpiperidine, phenylhyoscyamine, piperazine, piperidine carboxylic acid, piperidine, polypeptides, isopentenol lipids, pyridazine and its derivatives, pyridine, pyrimidine 2'-deoxyribonucleoside, pyrimidine nucleoside, pyrimidine, quinoline carboxylic acid, quinoline, steroid esters, steroids, tetrabenzoquinone, tetracycline, tetrahydroisoquinoline, thienopyridine, thiophene, hyoscyamine alkaloids, xylene, yohimbine alkaloids or their derivatives or combinations thereof.

158. The pharmaceutically acceptable salt of claim 156 or 157, wherein the pharmaceutical compound comprises acarbose, amorol, acarboxidine, alfentanil, alfuzosin, aripiprazole, amitriazine, amoxicillin, hexamethylmelamine, altropane, axidiclofen, amidinenicillin, aminolevulinic acid, amisulpride, amoxicillin, ampicillin, amrubicin, triamcinolone, aripiprazole, asenapine, atemexazole, AV-412, azapirolone, azatadine, bamectin, barnidipine, benidipine, bifenproxetine, bleomycin, bromelain, branicerin, buffentanil, bupivacaine, buspirone, calipexole, cariprazine, cassospirant, cathinone. Cefaclor, Cefadroxil, Cefdinir, Cefprozil, Cefadroxil, Cefalothin, Cefadroxil, Quinoerythromycin, Cetirizine, Chlorpyrimethanil, Librium, Chlortetracycline, Cilansetron, Clozapine, Dafopritin, Dapiprazole, Dasatinib, Disepine, Diethylamine benzophenone, Domperidone, Dozolidine, Dovitinib, Doxapram, Doxazosin, Doxycycline, Drotaverine, Edompex, Ifluconazole, Exalucin, Erudoline, Enalapril, Enzatolin, Epradone, Ergonovine, Ergotamine, EVT-101, Ezastastat, Faneclin, Fempresley, Finafloxacin, Flavoxel, Flubancelin, Flunarizine, Flupyridamole, Hexyl Aminolevulinate, Hydroxyzine, Eraprin, Ipraridone, Miconazole Danazine, Indinavir, Josamycin, Ketamine, Ketotifen, Lapatinib, Larazotide, Lesoprene, Levobupivacaine, Levocetirizine, Lidocaine, Linaloolide, Lofexidine, Cefaclor, Lopipiprazole, Loxapine, Lysergic acid diacetamide, Manidipine, Mepiprazole, Mabifocaine, Methoxycycline, Methylaminolevulinate, Methylergonovine, Mesiergotamine, Miglitol, Motisanib, Mosonicin, Naloxone, Naluzotan, Nefazodone, Nettopitan, Olanzapine, Olanzapine, Ondansetron, Oxytetracycline, Palonosetron, Piperipelone, Benzotriazine, Phenoxybenzamine, Pirenzepine, Pirenzepine, Pituitaridine, Promocaine, Prazosin, Prafuramid prx-08066, pyrimethamine, quetiapine, RAF-265, raloxifene, ranolazine, reboxetine, remifentanil, resveratrol, reserpine, rifampin, rifapentine, rocuronium bromide, ropivacaine, rupatadine, safenamide, saxagliptin, septoprolol, SNX-5422, sorimycin, sufgoli, SUVN-502, talac ferritin α, telithromycin, terazosin, buphenazine, ticlopidine, tepififibidine, tizanidine, tofacitinib, trabectedin, trazodone, trimethoprim, trimethoprim, temasolazoline, valacyclovir, valganciclovir, vallociclovir, vatocitabine, verneclax, voglibose, yohimbine, ziprasidone, zolquida, or combinations thereof.

159. The pharmaceutically acceptable salt of any one of claims 125-132, wherein the pKa of the pharmaceutical compound is about 8 to about 9.

160. The pharmaceutically acceptable salt of claim 159, wherein the pharmaceutical compound comprises 1-benzopyran, 1-benzothiaran, 1-phenyltetrahydroisoquinoline, alcohols, polyols, amines, amino acids, peptides, aminoquinoline and derivatives, androstened steroids, acetanilide, anisole, aryl sulfide, hydroquinone, benzylsulfonamide, benzo-1,4-dioxane, benzodiazepine, benzoic acid and derivatives, benzoquinoline, benzylamine, benzyl ether, benzylpiperidine, β-lactam, biphenyl and derivatives, carbazole, carbohydrates and carbohydrate conjugates, carbonyl compounds, carboxylic acid derivatives, phenolic peptides, dibenzo[a]azine, dibenzo[thio]azine, dibenzo[oxo]azine, diphenylacetonitrile, diphenylfuran, diphenylmethane, ethers, fatty acids and conjugates. Fentanyl, snowflake amine type Amaryllidaceae alkaloids, halobenzenes, hydrogenated pyridine, imidazoline, indazole, indole, indoloquinoline, isoquinolinone and its derivatives, isoxazoline, lysergic acid and its derivatives, methoxybenzene, monoterpenoids, morpholine, n-alkylindole, naphthidine, oxadiazole, pentacarboxylic acid and its derivatives, phenethylamine, phenothiazine, phenothiazine, phenoxy compounds, benzylamine, phenylnaphthalene, phenylpiperidine, phenylpropane, phenylpyridine, phenylpyrrolidine, phenylquinoline, piperazine, piperidine carboxylic acid and its derivatives, purine, pyrimidine and pyrimidine derivatives, pyrrolylpyridine, quinoline carboxamide, quinoline carboxylic acid, styrene, substituted pyrrole, sulfonylaniline, tetracarboxylic acid and its derivatives, thiazole, thiophene carboxylic acid and its derivatives, trifluoromethylbenzene, xylene or its derivatives or combinations thereof.

161. The pharmaceutically acceptable salt of claim 159 or 160, wherein the pharmaceutical compound comprises acepromethazine, acephenanthroline, ararubicin, avavastin, afatinib, afoxifene, aranoxin, amiodarone, aminon-13, ammonium molybdate, aminonaphthylfentanyl, amorolfen, amoxapine, acridine, amicaine, anamoxapine, anirilidine, apirin, acetonide, aclonidine, articaine, azoxifen, azimadolin, aspartame, astemizole, atrasentan, azelastine, azithritol, bedaquiline, benzylfentanyl, bosutinib, bromoxynil, bromhexine, bukrazine, bupivacaine, bupivacaine, bupropion, buprofentanyl, carbidopa, captopril, carbifexamine, carfentanil, carbapenem ... Videlol, Cefminox, Cefotiam, Sigosvir, Cevimeline, Chlorcyclophosphamide, Chlorprocaine, Clopidogrel, Chlorpyrifos I-131, Cinnarizine, Ciprofloxacin, Cisapride, Clarithromycin, Chlorpheniramine, Clomocycline, Clonidine, Clopidogrel, CNS-5161, Cocaine, Cyclopemycin, Cyclopentolate, Cycloserine, Cyproheptadine, Davallin, Daunorubicin, DDP-225, Demeclocycline, Delencyclophosphamide, Desvenlafaxine, Dicyclovir, Dihydroergotamine, Diltiazem, Dimethicone, Diphenhydramine, Diphenhydramine, Diphenoxylate, Diphenhydramine, Dofetilide, Donepezil, Dotarizine, Doxorubicin, Doxylamine, Drolidine, D-Serine, Dacronin, Edioxetine, Edivorcetin Iraqda, eletraptane, elegliflozin, emesostine, enoxacin, eperisone, epinastine, adrenaline, epirubicin, erythromycin, esoxacin, famotidine, fasudil, fentanyl, flupentixol, fluphenazine, flurazepam, frodisiac, freundromycin B, gaboxetine, gadofosamide, galantamine, galafloxacin, gatifloxacin, grelasatinib, glucosamine, glypromate, granisetron, gapfloxacin, haloperidol, hydrocodone, hydromorphone, idarubicin, imatinib, imolamin, indium pentiate In-111, iroxadin, isominir, isoproterenol, isocetirizine ... Levobupivacaine, Cobadine, Lincomycin, Lobeline, Lofentanil, Lomefloxacin, L-Threonine, Thiantrone, Lumapizoline, Lurasidone, LY-517717, Demamagazine, Masetinib, Meclozine, Mepiridazine, Mepiridazine, Mepiridazine, Mesodazine, Midodrine, Miglustat, Miglustat, Mimosine, Minocycline, Moxicillin Naloxetine, Nebivolol, Nafenavir, Nicardipine, Nicergoline, Nicotine, Norepinephrine, Norfloxacin, Normethadone, Oxcarpiperone, Oxymethylfentanil, Ophenazine, Osimertinib, Obubucaine, Oxibutin, Oxycodone, Hydroxybenzylphenidate, Palfurapine, Palbociclib, Palpanridone, Palilodane, Pargilin, PBT-1033, PeritinibTrisodium pentiate calcium, trisodium pentiate zinc, pentostatin, perphenazine, meperidine, p-flufentanyl, indole, fenmetrazine, bensulfuron-methyl, pimozide, pipampazone, pipexazol, piperoxithiazide, pyridinole, ponatinib, PPI-1019, pricaine, procaine, prochlorperazine, proflavin, promecaine, piperazine, propyrazole, propylthiazide, prooxycaine, protoprolol, prunasine Carpipride, PRX-07034, Quinolidone, Quinuprin, Rabemodil, Ranitidine, Rasagiline, Remasiamide, Remopride, Lenzapride, Rifabutin, Rifarazil, Relapade, Risperidone, Rivasidine, Robazotane, Lorapitane, Roxatidine Acetate, Saquinavir, Salfloxacin, Salizotan, Selegiline, Serine, Serindole, Sincalitone, Sitagliptin, Soriberi Naxin, Sparfloxacin, Sodomycin, Sufentanil, Sulpiride, Taclopramide, Talaposta, Tamoxifen, Taliquida, Technetium TC-99M Tetraphosphine, Tegaserod, Terbinafine, Terconazole, Tetracaine, Tetracycline, Thiophanolfentanil, Thiproprazole, Thioridazine, Tevothiazol, Somizole, Thionepril, Tigecycline, Tocainide, Topazol, Toremifen, Trifluoperazine, Trimebutine, Trimebutine Benzylamine, Triprine, Triptoridine, Tromethamine, Tubocurane, Udenafil, Varanoslin, Veripani, Venlafaxine, Viveverol, Verazorone, Veroxadone, Vincronidine, Vincristine, Vindesine, Vinorelbine, Laurylamine, Vortioxetine, Zaridroden, Zantinol, Zanapezil, Zotepine, Zincylthiasol, α-Methylfentanyl, α-Methylthiofentanyl, β-Hydroxythiofentanyl, or combinations thereof.

162. The pharmaceutically acceptable salt of any one of claims 125-132, wherein the pKa of the pharmaceutical compound is about 9 to about 10.

163. The pharmaceutically acceptable salt of claim 162, wherein the pharmaceutical compound comprises 1-benzopyran, 1-benzothiaran, 1-hydroxy-4-unsubstituted benzene compounds, 4-quinoline methanol, 5'-deoxy-5'-thionucleoside, amine, amino acid, peptide, aminophenyl ether, aminoquinoline, acetanilide, anisole, anthraquinone, hydroquinone, benzyl sulfonamide, benzo-1,4-dioxane, benzodiazepine, benzoic acid, benzyl nitrile, benzoquinoline, benzoxazinone, benzoyl, benzyl alcohol, benzyl ether, benzylpiperidine, β-lactam, biphenyl, bisphosphonates, carbazole, carbohydrates and carbohydrate conjugates, indigo, phenolic peptides, dibenzodiazepines, dibenzothiocyanates, dibenzooxazines, dicarboxylic acids, diphenylacetonitrile, diphenylmethane, bis(benzopyrene) Terpenoids, ethers, fentanyl, glycerophosphoserine, halobenzenes, heteropeptides, hydrogenated pyridine, hydrogenated quinoline, hydroxypyridine, indazole, indole carboxylic acid, indole, indoline, indoroquinoline, indole carboxylic acid, isoquinoline quinone, lysergic acid, methoxybenzene, naphthidine, nitrobenzene, nitroquinoline, organic sulfonic acids, pentacarboxylic acids, phenethylamine, fenilam, phenothiazine, phenoxazine, phenoxy compounds, phenoxyacetic acid, phenylacetamide, phenylbutylamine, benzylamine, phenylpiperidine, phenylpropane, phenylhyoscyamine, piperazine, piperidine carboxylic acid, pregnane steroids, purines and purines, pyridinium, quinoline carboxylic acid, quinolones, steroid esters, styrene, substituted pyrroles, sulfonylaniline, tametriline, thiophene carboxylic acid, toluene, trifluoromethylbenzene, tryptamine, tyrosol or derivatives thereof or combinations thereof.

164. The pharmaceutically acceptable salt of claim 162 or 163, wherein the pharmaceutical compound comprises (3S)-3-methyl-D-aspartic acid, isocortin, 13-deoxydoxorubicin, 3-allyl fentanyl, 3-methylfentanyl, 4-phenylfentanyl, 7-hydroxyspicoline, acebutolol, S-adenosylmethionine, adoloxin, alendronate, aliximab, aliskiren, amotriptan, alogliptin, alprazolam, ambroxol, amibelonone, amikacin, amigonic acid, aminocontin, amitriptyline, and ambroxol. Dihydropyridine, Amphotericin B, Atazoline, Ampicillin, Apramycin, Abaclofen, Abexocin, Abutamine, Afortrol, Arelolomo, Aprolol, Arylacetamide, Atenolol, Atoxitin, Atoxiban, Atropine, Azithromycin, Bacitracin, Baclofen, Babuterol, Badoxifene, Betcalin, Benflurex, Benzatropine, Benzylphenamine, Benzylpenicillin, Thiazolyl-Lysine, Betastin, Bepridil, Besifloxacin, Betahistine ... Solomon's, Bodnisolone, Butofencin, Bromhexine, Bromdapoxetine, Brompheniramine, Butifrolol, Blavallorone, Butenafine, Cabergoline, Canphosphatamide, Carbocysteine, Cardilolol, Caspofungin, Sildenafil, Cefalexin, Cefoloza, Celilolol, Chlorpheniramine, Chlorpromazine, Chlorprothiazide, Cilastatin, Cincocaine, Cialis, Citalopram, Clomastine, Clenbuterol, Chlorcarmine, Clofazimine, Clomiphene, Clomipramine, Cobitinib, Codeine, Colestipol, CP-122721, Cymemazine, Cyclobenzaline, Cyclomethasone Acetaminophen, Cystine, Indigoferazone, Dapavancin, Dapoxetine, Datopromycin, Dalinpacin, Desclopramide, Demetriline, Desloratadine, Dexbromin, Dexclopramide Maleate, Dextromethorphan, Dextromethorphan, Dextropropoxyphene, Dextrothyroxine, Dezocine, Diphenoxyphene, Diphenoxyphene, Diphenidol, Dipiformin, Diphenoxyphene, Diphenoxyphene, Dierythromycin, D-methionine, Dobutamine, Dopamine, Doripenem, Duthipine, Doxepin, Dronedarone, Duloxetine, Encani, Enclomiphene, Ephedrine, EpiceptNP-1, Eribulin, Ertapenem, Etapril, Esmolol, Ethambutol, Profenamide, Ethylmorphine, Eticacaine, Ethyltryptamine, Fennoterol, Fensipride, Ferrous Glycine, Fexofenadine, Flannib, Fingolimod, Flucainide, Fluoxetine, Fluspiline, Fluvoxamine, Formoterol, Freund's Mycelium, Gabapentin, Gadobacterium, Gadolinium Trisodium, Gadolinium Dimeglumine, Gadolinol, Gadoxetine, Gemmifloxacin, Glutamic Acid, Glutathione, Glutathione Disulfide, Glycine, Golomod, Gorgliptin, Granisetron, Haloferone, Heroin, Hecticine, Heccaine, Histamine, Histidine, Homatropine Huperzine A, Huperzine B, Hydroxybufenazole, Hydroxychloroquine, Hyoscyamine, Ibandronate, Efenidil, Imipramine, Indacaterol, Ioflupane I-123, Irinotecan, Iotaline, Isopin, Ivabradine, K201, Kanamycin, Labetalol, L-Alanine, L-Aspartate, L-Citrile, L-Cysteine, L-Lercanidipine, Leukotriene C4, Levofloxacin, Levoamlodipine, Levobetalol, Levobuprofen, Levodopa, Levomethadone, Levomilnacipran, Levofenoxate, Levothyroxine, L-Glutamine, Linagliptin, Iothrolone, Compound Thyroxine, L-Isoleucine, LJP1082, L-Leucine, Lometrexed, Loperamide, L-Phenylanine, L-Threonine, L-Tryptophan, L-Tyrosine, Benfluorenol, L-Valine, Lysylcycline, Sulfamethoxazole, Magnesium Glycine, Mefloxacin, Melphalan, Meropenem, Metarhamnol, Methadone, Acetatemethadone, Methionine, Levomethazine, Metoxamine, Methyldopa, Methylphenidate, Methemolol, Methoxane, Metoclopramide, Metoprolol, Methyltyrosine, Mexiletine, Mibeprazole, Milnacipran, Mirabelon, Mitansinol, Mitoxantrone, MN-305, Morphine, Moxifloxacin, Nadolol, Naftifine, Namefen, Naratriptan, Naronapride, Natal Mycin, Nemonoxacin, Netilmicin, Nitroarginine, NPS-2143, NS-2359, Nystatin, Oglufanine, Odanoterol, Olopatadine, Homoharringtonine, OPC-28326, Osinarine, Osanetin, Oseltamivir, Oxaniquine, Olofolin, Serotonin, Oxenolol, Pamidronate, Paroxetine, Paroxetine, Penicillamine, Pentoxyverine, Pergolitide, Phenylephrine, Indoleamine, Feniramine, Phentolamine, Phenylephrine, Phenylephrine, Pholcodine, Phosphatidylserine, Piperazine, Indoleolol, Piperazine, Pirarubicin, Pirbuterol, Pifenamic acid, Zinc prasinose, Pracinositol Pramolol, Procainamide, Procaterol, Procycline, Promethazine, Promirtine, Propafenone, Propoxyfen Naphthylsulfamate, Propranolol, PRX-03140, Pseudoephedrine, PX-478, Quarfloxin, Quinidine, Quinidine Barbiturate, Quinine, Repinovantan, Retaparin, Ribomycin, Ritodrine, Rizatriptan, Ronacarb, Roxithromycin, Salbutamol, Salmeterol, Sarredutan, Selenomethionine, Seroxetine, Sertraline, Sibutramine, Silodosin, Cilamecone, Sorabelon, Sotalol, Spectinomycin, Spiramycin, Sumatriptan, Sunitinib, Tamsulosin, Tandutinib Tapendarone, TAS-108, Taurine, Tedesamine, Terbutaline, Terfenadine, Telmilipin, Tersofencin, Tetrodotoxin, TG-100801, Tigaben, Ticapride, Tilmicosin, Timolol, Tobramycin, Topotecan, Tramadol, Transphenylcyclopropamine, Triethylenetetramine, Trifluoropromethazine, Trihexyphenidyl, Trimetazidine, Trimipramine, Travafloxacin, Tyramine, Ubenimex, Vancomycin, Vandetanil, Vareniclan, Vecuronium bromide, Verapamil, Vernacalan, Vigabatrin, Vilanterol, Vildagliptin, Zolmitriptan, α-Methylacetylfentanyl, α-Methylfentanyl, β-Methylfentanyl or combinations thereof.

165. The pharmaceutically acceptable salt of any one of claims 125-132, wherein the pKa of the pharmaceutical compound is about 10 to about 13.

166. The pharmaceutically acceptable salt of claim 165, wherein the pharmaceutical compound comprises 2,6-dimethyl-3-benzo[a]arene, alkaline earth metal oxides, alkyl thiols, amines, amino acids, peptides, aminopyridine, aminoquinoline, hydroquinone, benzoic acid, benzo[a]quinoline, β-lactam, cholic acid, alcohols, biphenyl, bisphosphonates, carbazole, carbohydrates and carbohydrate conjugates, carboxylic acid derivatives, cyclohexylamine, phenolic peptides, dibenzo[a]azine, diphenylmethane, ethers, fatty acids and conjugates, guanidine, halobenzenes, heteropeptides, indole carboxylic acids, indole, indoline, monoterpenoids, n-arylamides, organic sulfonic acids, peptide-peptide hybrids, phenethylamine, fenilam, phenylbutylamine, benzylamine, phenylpiperidine, phenylpropane, phenylpropylamine, phenylpyridine, piperidine carboxylic acid, purines and purine derivatives, pyrazolylpyridine, pyrimidines and pyrimidine derivatives, tetracarboxylic acids, tryptamine, urea, xylene or its derivatives or combinations thereof.

167. The pharmaceutically acceptable salt of claim 165 or 166, wherein the pharmaceutical compound comprises 2-iminobiotin, abaricidin, ABT-510, afanotoxin, guanidine, acetaminophen, avimopanol, amantadine, AMD-070, amifostine, aminocaproic acid, amodiaquine, amphetamine, anatibant, apomorphine, argatroban, averapamil, atemod, adipidil, bedoradine, benzodiazepine, betanidine, bisifafine, bivalirudin, brotamethasone, buprenorphine, butorphanol, butiline, capreomycin, urea peroxide, cefotoxin, ceritinib, cetrorexate, chlorhexidine, chloroquine, p-chlorophenbutanol, cinacalcet, trifluoroacetic acid, cortisone, Cr66 5. Creatine, Crizotinib, Cysteine, CZEN002, Davapiridine, Dafenacin, Isoquinoline, Deferoxamine, Degarelix, Decasate, Denibulin, Desipramine, Diloxacin, Desmopressin, Dexfenfluramine, Dextroamphetamine, Diethylseminated spermine, Dihydrostreptomycin, Diisopropyridine, Eflunomide, Envelopromycin, Etorphine, Phenylephrine Fencanfamin, fenfluramine, fenfluramine, fennorphanine, fexordine, frefiban, furotriptan, furazolidone, gadoteric acid, gadoterol, γ-aminobutyric acid, ganirilac, gentamicin, gonadorelin, goserelin, guanazolidin, guanethidine, guanidine, halopanyltriol, hesonaline, histamine relin, hydroxyproline, hydroxystilbene hydroxyethylsulfonic acid, ibutilide, atebandonide, Imipenem, Indapoxetine, Indecarbide, Iodobenzylguanidine, Iodobenzylguanidine sulfate I-123, Imometidine, Labedimir, L-Aminocarnitine-succinyl-leucyl-arginine-diethylacetal, Lanrethide, L-arginine, L-ornithine, Levodosethionine, Levocarbastine, Lysine amphetamine, Lisinopril, Lixifenatide, L-lysine, Lorcaserin, L-proline, Magnesium oxide, Maprotiline, Maraviro, Mecarmine, Memantine, Mefenamic acid, Metformin, Metformin, Midomafelamine, Nafarelin, Nabuphine, Naltrexone, Naphazoline, Nelamesin, Neridonic acid, Nintedanib, Nor-noha, Nortriptyline, Benzylpropionic acid, Onipeptide, Octreotide, Olcegepant, O Levancin, Ornithine, Omisaban, Oxymetazoline, Hydroxymorphine, Pabistat, Paciletide, Pemetrexed, Pentamicil, Pentazocine, Peramivir, Piperacillin, Phenylephrine, Phentermine, Pimazidine, Pimagatem, Piracetam, Presalifos, Polymyxin B Sulfate, Pozaniclone, Pramipexole, Pregabalin, Prezatide, Primaquine, Flusalamide, Chlorguanidine, Propranolol, Protriptyline, Tiamethoxam, Quinacrine, Ramolane, Rifaximin, Amantadine, Rivanoline, Romidixin, Ropinirole, Rotigotine, Salazine, Saplatin, Serotonin, SGS-742, Sitamoebasil, SNS-032, Somatostatin, Spermine, SQ-109, Squalamine, Streptomycin, T131, Tafenoxane, TarlotrexineTanspiramycin, tecasmizole, tenosynovine, terlipressin, temorepinephrine, tecocloprid, tetrahydrozoline, tezapanide, tepiramycin, tirofiban, tolazoline, tolterodine, taurine, tranexamic acid, triptorelin, uracil, urea C-13, vapitaxine, vintafolide, purpuric acid, WX-UK1, xylometazoline, zanamivir, or combinations 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 pKa of the pharmaceutical compound is at least 2.

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

5.

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

172. The pharmaceutically acceptable salt of claim 168, wherein the pKa of the pharmaceutical compound is 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.

174. The pharmaceutically acceptable salt of claim 173, wherein the pKa of the pharmaceutical compound is at least 5.

175. The pharmaceutically acceptable salt of claim 173, wherein the pKa of the pharmaceutical compound is 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 weight osmotic molar concentration lower than that of a solution containing the composition comprising the salt of the pharmaceutical compound and the salt of the complexing agent.

177. The pharmaceutically acceptable salt of any one of claims 124-176, wherein, compared to a composition (i) free of the complexing agent or (ii) wherein the pharmaceutical compound does not complex with one or more of the acidic functional groups of the complexing agent, the pharmaceutically acceptable salt improves the 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%.

178. The pharmaceutically acceptable salt of any one of claims 124-177, wherein, compared to a composition (i) free of the complexing agent or (ii) wherein the pharmaceutical compound does not complex with one or more of the acidic functional groups of the complexing agent, the pharmaceutically acceptable salt improves the solubility of the pharmaceutical compound by about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 20, about 30, about 40, or about 50 times.

179. A pharmaceutically acceptable salt according to 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 sulfobutyl ether-β-cyclodextrin (SBEBCD).

183. The pharmaceutically acceptable salt of claim 124, wherein the pharmaceutically acceptable salt, when formulated as a solution, has a weight osmotic molar concentration lower than that of a solution comprising a composition containing the salt comprising the pharmaceutical compound and the salt comprising the complexing agent.

184. The pharmaceutically acceptable salt of claim 124, wherein the drug is formulated for subcutaneous, intramuscular, sublingual, oral, rectal, vaginal, or intranasal administration.

185. The pharmaceutically acceptable salt of claim 124, wherein when prepared as a solution, the weight osmolar concentration of the pharmaceutically acceptable salt does not exceed about 850 mOsm / kg.

186. The pharmaceutically acceptable salt of claim 62, wherein the pH of the pharmaceutically acceptable salt is from 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 as a counterion of 1 to 10 molecules of the pharmaceutical compound.

189. The pharmaceutically acceptable salt of claim 124, wherein the complexing agent further comprises a nonpolar 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 with the nonpolar pore.

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

1.

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

2.

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

3.

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

4.

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

5.

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

5.

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

198. The pharmaceutically acceptable salt of claim 124, wherein the solubility of the pharmaceutical compound as a salt in an aqueous medium is less than about 10 mg / ml.

199. The pharmaceutically acceptable salt of claim 124, wherein the solubility of the pharmaceutical compound as a salt in an aqueous medium is less than about 5 mg / ml.

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

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

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, copanlixetine, levodopa, tigecycline, naloxone, amikacin, 1-amantadine, 2-amantadine, rimantadine, amipridine, rapamycin, clonidine, morphine, hydrocodone, sumatriptan, ropivacaine, bupivacaine, diphenhydramine, granisetron, dechlorin, 2-fluoro-dechlorin, or caspofungin.

204. The pharmaceutically acceptable salt of any one of claims 124-203, wherein the pharmaceutical composition comprises a GABAergic agent.

205. The pharmaceutically acceptable salt of claim 204, wherein the GABAergic agent comprises baclofen, gaposidol, or muscarinic acid, or combinations thereof.

206. A pharmaceutically acceptable salt according to any one of claims 124-203, wherein the pharmaceutical compound comprises an α-2 agonist.

207. The pharmaceutically acceptable salt of claim 206, wherein the α-2 agonist comprises clonidine, guanfasin, or tizanidine, or combinations thereof.

208. A pharmaceutically acceptable salt as claimed in any one of claims 124-203, wherein the pharmaceutical compound is an ophthalmic preparation.

209. The pharmaceutically acceptable salt of claim 208, wherein the ophthalmic preparation comprises acetylcholine, atropine, azelastine, bromonidin, cyclopentolate, ketotifen, levobunolol, olopatadine, spirocarpine, promecaine, tetracaine, timolol, or tropicamide.

210. A pharmaceutically acceptable salt according to 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 of two or more thereof.

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

213. The pharmaceutically acceptable salt of claim 212, wherein the antibiotic comprises amikacin, amoxicillin, ampicillin, azithromycin, aztreonam, cefaclor, cefadroxil, cefalexin, cefazolin, cefdinir, ceftoran, cefepime, cefdil, cefixime, cefmetazole, cefoperazone, cefotaxime, cefotetan, cefotaxime, cefoxitin, cefpodoxime, cefprozil, cefuroxime, ceftazidime, cefotaxime, cefoproxime, cefotaxime, cefotaxime, cefuroxime, ceftriaxone, cefuroxime, cefalexin, cefepime, cefepime, cefradine, ciprofloxacin, clarithromycin, clomiphene, colistin, dapoxetine. Vancomycin, dapoxetine, dapoxetine, doripenem, doxycycline, ertapenem, ilacycline, erythromycin, fosfomycin, gentamicin, imipenem, kanamycin, lefamolin, levofloxacin, linezolid, lincomycin, meropenem, metronidazole, minocycline, moxifloxacin, nalidixic acid, neomycin, nitrofurantoin, orivoxetine, penicillin, piperacillin, polymyxin B, quinupristine, retaparin, rifampin, streptomycin, sulfacetamide, sulfadiazine, sulfamethoxazole, sulfasalazine, sulfasalazine, sulfisoxazole, teicoplanin, tervacancin, tetracycline, tigecycline, tobramycin, trimethoprim, or vancomycin or combinations thereof.

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

215. The pharmaceutically acceptable salt of claim 214, wherein the anticoagulant or thrombolytic agent comprises alteplase, argatroban, bivalirudin, fondaparinux sodium, lepirudine, streptokinase or urokinase or combinations thereof or two or more thereof.

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

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

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

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

220. A pharmaceutically acceptable salt according to any one of claims 124-203, wherein the pharmaceutical compound is an antitumor drug.

221. The pharmaceutically acceptable salt of claim 220, wherein the antitumor drug is afatinib, alectinib, arisetinib, axitinib, bosutinib, cabozantinib, cannetinib, carfilzomib, sildenafil, ceritinib, cimetidine, cobitinib, dabrafenib, darazabine, dasatinib, decarsetinib, dovitinib, erlotinib, etorcoxib, felanib, grelasatinib, ibrutinib, ederalipix, imatinib, ispinox, ixazomib, lapatinib, Lenvatinib, lincitinib, lonafab, masatitinib, motisanib, nilotinib, nintedanib, odandarbitril, olaparib, onanacipiride, osimertinib, palbociclib, pazopanib, perititinib, ponatinib, regorafenib, renalapadi, ruxolitinib, celicil, sorafenib, sunitinib, tandutinib, tepififib, tofacitinib, vandetanib, varitinib, varitinib, vatalani, veripabib, vemurafenib, vemodiginib, or combinations thereof or two or more thereof.

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

223. The pharmaceutically acceptable salt of claim 222, wherein the antiviral agent comprises abacavir, acyclovir, adefovir, amantadine, ampravir, atazanavir, bicretiravir, cidofovir, darunavir, dasabuvir, deraviridine, norinosine, dolutegravir, efavirenz, erteiravir, emtricitabine, enfuvirtide, entecavir, famciclovir, foscarnet, ganciclovir, grazoprevir, imiquimod, Indinavir, lamivudine, lanimivir, ledipasvir, lopinavir, maraviro, nalfinavir, nevirapine, olbitasvir, oseltamivir, pariravir, penciclovir, peramivir, prasafone, podophyllotoxin, raltegravir, ribavirin, rilpivirine, ritonavir, saquinavir, sofosbuvir, stavudine, tenofovir, telanavir, trifluuridine, valacyclovir, valganciclovir, zanamivir, or zidovudine or combinations thereof.

224. A pharmaceutically acceptable salt according to any one of claims 124-203, wherein the pharmaceutical compound comprises a cardiovascular drug.

225. The pharmaceutically acceptable salt of claim 224, wherein the cardiovascular drug comprises bromide, dobutamine, dopexamine, eprostol, esmolol, iloprost, nesiritide, nitroglycerin, norepinephrine or phenylephrine, or combinations thereof or two or more thereof.

226. A pharmaceutically acceptable salt according to any one of claims 124-203, wherein the pharmaceutical compound comprises a central nervous system depressant.

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

228. A pharmaceutically acceptable salt according to any one of claims 124-203, wherein the pharmaceutical compound comprises a central nervous system stimulant.

229. The pharmaceutically acceptable salt of claim 228, wherein the central nervous system stimulant comprises amphetamine, cocaine, dextromethorphan, dextromethorphan, ephedrine, lysine amphetamine, methylphenidate, methylphenidate, modafinil, phenylephrine, pseudoephedrine, or sibutramine, or combinations thereof, or two or more thereof.

230. A pharmaceutically acceptable salt according to 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, dibutylcaine, eticaine, levobupivacaine, lidocaine, mabivocaine, prilocaine, procaine, prilocaine, ropivacaine, or tetracaine or combinations thereof.

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

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

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

235. The pharmaceutically acceptable salt of claim 234, wherein the anti-migraine drug comprises amotriptan, avetriptan, doniptriptan, eletriptan, frotriptan, lamitentan, nalatriptan, rizatriptan, sumatriptan, or zolmitriptan or combinations thereof.

236. A pharmaceutically acceptable salt according to any one of claims 124-203, wherein the pharmaceutical compound comprises an anti-Parkinson's disease drug.

237. The pharmaceutically acceptable salt of claim 236, wherein the anti-Parkinson's disease drug comprises amantadine, apomorphine, benzalkonium chloride, benserazide, bromocriptine, cabergoline, carbidopa, entacapone, foscarbidopa, foscarbidopa, levodopa, melevopa, pramipexole, rasagiline, ropinirole, rotigotine, safenamide, selegiline, tocapone, or trihexyphenidyl or combinations thereof.

238. A pharmaceutically acceptable salt according to 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 avastin, brompheniramine, cetirizine, chlorpheniramine, chlormastine, cyproheptadine, desloratadine, dextrochlorpheniramine, diphenhydramine, doxylamine, fexofenadine, hydroxyzine, levocetirizine, loratadine, meclopramide, promirtine, or tropineamine, or combinations thereof.

240. A pharmaceutically acceptable salt according to 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 the pharmaceutical compound comprises an opioid.

243. The pharmaceutically acceptable salt of claim 242, wherein the opioid substance comprises buprenorphine, butorphanol, codeine, fentanyl, heroin, hydrocodone, hydromorphone, levonorphine, pethidine, methadone, morphine, naloxone, naltrexone, nalmefenamic acid, oxycodone, oxymorphone, pentazocine, sufentanil, tapentadone, or tramadone, or combinations thereof, 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. A pharmaceutically acceptable salt according to any one of claims 124-203, wherein the pharmaceutical compound comprises amipyridine, amifostine, aminocaproic acid, argatroban, asenapine, atropine, bivalirudin, cisatracurium, deferoxamine, desmopressin, gabapentin, lurasidone, milrinone, nicotine, octreotide, pregabalin, rocuronium bromide, terbutaline, tirofiban, tranexamic acid, vecuronium bromide, naprafenamide, or any combination thereof.

247. The pharmaceutical composition according to any one of claims 1-123, wherein at least one of the acidic functional groups is associated with Na. + K + Mg 2+ Ca 2+ H3O + or a combination of cation complexes thereof.

248. A pharmaceutically acceptable salt according to any one of claims 124-246, wherein at least one of the acidic functional groups is associated with Na. + K + Mg 2+ Ca 2+ H3O + or a combination of cation complexes thereof.

249. A method for preparing a pharmaceutical composition, comprising combining in a suitable liquid medium: a) a drug compound or its enantiomers, mixtures of enantiomers or isotopic variants in a free base form, wherein the drug compound comprises at least one basic nitrogen atom and has 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 ailment, comprising administering a pharmaceutical composition as described in any one of claims 1-123, 247 or a pharmaceutically acceptable salt as described in any one of claims 124-246, 248.

Images