Pharmaceutical compositions comprising atorvastatin, or a salt thereof, and a liquid carrier

Abstract

Disclosed are pharmaceutical compositions comprising atorvastatin or a salt thereof and a liquid carrier. Also provided are methods of administering the compositions, and methods of treating a subject in need thereof with the compositions.

Description

[0001] PHARMACEUTICAL COMPOSITIONS COMPRISING ATORVASTATIN, OR A SALT THEREOF, AND A LIQUID CARRIER

[0002] RELATED APPLICATIONS

[0003] This application claims the benefit of U.S. Provisional Application No. 63 / 636,534, filed April 19, 2024, the contents of which are fully incorporated by reference herein.

[0004] STATEMENT OF GOVERNMENT SUPPORT

[0005] This invention was made with government support under SBIR grant no. R43NS119081 awarded by the National Institute of Health (NIH). The government has certain rights in the invention.

[0006] BACKGROUND

[0007] Pharmaceutical compositions provide a vehicle for therapeutic agent delivery. Parenteral pharmaceutical compositions are often liquid pharmaceutical compositions. Liquid particle free parenteral pharmaceutical compositions, i.e. solutions, can be sterile filtered enabling safe and easy manufacturing. For oral pharmaceutical dosing forms, liquid compositions can be also of advantage, as they allow for graded dosing by volume. In addition, they are useful in patients which are not able to swallow tablets or capsules or where a gastric tube allows for dosing of fluids only.

[0008] The need for liquid pharmaceutical compositions including multiple therapeutic agents is especially apparent for parenteral administration, as administration of multiple therapeutic agents in a single administration event may improve patient compliance and reduce waste generated from multiple parenteral administration devices. Accordingly, there is a need in the art for the development of liquid pharmaceutical compositions.

[0009] SUMMARY

[0010] In certain aspects, provided is a pharmaceutical composition comprising atorvastatin, or a salt thereof, and a liquid carrier. The liquid carrier comprises ethylenediaminetetraacetic acid (EDTA), or a salt thereof. In further aspects, provided is a pharmaceutical composition comprising atorvastatin, or a salt thereof, and a liquid carrier. The atorvastatin, or salt thereof, is dissolved within the liquid carrier at a concentration of at least 0.7 mg / mL.

[0011] In further aspects, provided is a pharmaceutical composition comprising atorvastatin calcium and a liquid carrier. The atorvastatin calcium is dissolved within the liquid carrier at a concentration of about 2 mg / mL. The liquid carrier comprises: about 0.3% (w / w) meglumine or a salt thereof; about 3% (w / w) propylene glycol; about 1% (w / w) polysorbate 80; about 0.07% (w / w) tetrasodium EDTA; and 93% to 97% (w / w) 10 millimolar phosphate in water.

[0012] In further aspects, provided is a method of administering atorvastatin to a subject comprising administering atorvastatin, or a pharmaceutically acceptable salt thereof, to the subject parentally.

[0013] In further aspects, provided is a method of administering atorvastatin to a subject comprising orally administering to the subject the pharmaceutical composition according to embodiments described herein.

[0014] In further aspects, provided is a method of administering a combination of atorvastatin, or a salt thereof, ceftriaxone, or a salt thereof, and levetiracetam to a subject comprising parenterally administering to the subject a pharmaceutical composition comprising atorvastatin, or a salt thereof, ceftriaxone, or a salt thereof, and levetiracetam.

[0015] In further aspects, provided is a method of administering a combination of atorvastatin, or a salt thereof, ceftriaxone, or a salt thereof, and seletracetam to a subject comprising parenterally administering to the subject a pharmaceutical composition comprising atorvastatin, or a salt thereof, ceftriaxone, or a salt thereof, and seletracetam.

[0016] In further aspects, provided is a method of administering a combination of atorvastatin, or a salt thereof, an SV2A agonist, and an antibiotic to a subject comprising parenterally administering to the subject a pharmaceutical composition comprising atorvastatin, or a salt thereof, an SV2A agonist, and an antibiotic.

[0017] In further aspects, provided is a method of treating a seizure disorder in a subject in need thereof comprising administering to the subject the pharmaceutical composition according to embodiments described herein. In further aspects, provided is a method of treating dyslipidemia in a subject in need thereof comprising administering to the subject the pharmaceutical composition according to embodiments described herein.

[0018] In further aspects, provided is a method of treating an infection in a subject in need thereof, comprising administering to the subject the pharmaceutical composition according to embodiments described herein.

[0019] In further aspects, provided is a method of treating epileptogenesis in a subject in need thereof, comprising administering to the subject the pharmaceutical composition according to embodiments described herein.

[0020] In further aspects, provided is a kit comprising a first container and a second container. The first container comprises atorvastatin, or a pharmaceutically acceptable salt thereof, and EDTA, or a pharmaceutically acceptable salt thereof. The second container comprises a pharmaceutically acceptable solution comprising water and propylene glycol.

[0021] DETAILED DESCRIPTION

[0022] In certain aspects, the present disclosure relates to the discovery that atorvastatin calcium can be readily dissolved in a pharmaceutically acceptable solution comprising ethylenediaminetetraacetic acid (EDTA), or a pharmaceutically acceptable salt thereof. Further experiments revealed that the inclusion of additional pharmaceutically acceptable excipients further enhance the solubility and stability of atorvastatin in the solution. The pharmaceutically acceptable solutions of atorvastatin described herein facilitate the administration of atorvastatin parentally and are also useful for administering atorvastatin orally to subjects who are in a state of reduced consciousness, have difficulty swallowing, or who suffer from a gastrointestinal disorder. Additional therapeutic agents can be added to the pharmaceutically acceptable solutions of atorvastatin described herein to facilitate the administration of multiple therapeutic agents to a subject.

[0023] Atorvastatin calcium (ATV-Ca, also called ATV) is a prescription medication used as a monotherapy or as combination treatment with ezetimibe for treatment of dyslipidemia. All currently marketed oral preparations of atorvastatin contain the calcium salt of atorvastatin, or more specifically, atorvastatin calcium trihydrate. This salt is selected over other salts, as, due to its low solubility, it can be manufactured in high purity and with high chemical stability. ATV is indicated as an adjunct to diet for reduction of elevated total cholesterol (total-C), LDL-cholesterol (LDL-C), apolipoprotein B, and triglycerides in adults, adolescents and children aged 10 years or older with primary hypercholesterolaemia including familial hypercholesterolaemia (heterozygous variant) or combined (mixed) hyperlipidaemia (Corresponding to Types Ila and lib of the Fredrickson classification) when response to diet and other nonpharmacological measures is inadequate.

[0024] Atorvastatin is also indicated to reduce total-C and LDL-C in adults with homozygous familial hypercholesterolaemia as an adjunct to other lipid-lowering treatments (e.g. LDL apheresis) or if such treatments are unavailable.

[0025] ATV is also indicated for the prevention of cardiovascular events in adult patients estimated to have a high risk for a first cardiovascular event, as an adjunct to correction of other risk factors.

[0026] Statins including atorvastatin have been shown to ameliorate the deteriorating effect of a cerebral stroke. If statins are not continued to be treated in patients with stroke, the risk of death and the debilitation score was higher as compared to patients which were continued on statins (if they had been dosed before on statins) or which were started to be dosed with statins upon arrival in the intensive care unit (BLANCO, M., et al. Statin treatment withdrawal in ischemic stroke: a controlled randomized study. Neurology, 2007, 69. Jg., Nr. 9, S. 904-910). Similar positive findings of statin treatment is reported in cardiovascular stroke. In critically ill patients, statin use in the intensive care unit was associated with reduced delirium, especially early during sepsis; discontinuation of a previously used statin was associated with increased delirium (MORANDI, Alessandro, et al. Statins and delirium during critical illness: a multicenter, prospective cohort study. Critical care medicine, 2014, 42. Jg., Nr. 8, S. 1899.). Statin treatment and especially atorvastatin treatment has been reported to reduce the risk to develop epilepsy if administered in patients suffering from glioblastoma, ischemic stroke, radiotherapy for nasopharyngeal carcinoma, intracranial hemorrhage, coronary revascularization following coronary occlusion, and in aged patients which are critically ill Atorvastatin had the most statistically significant association with epilepsy risk reduction in retrospective clinical studies (HUFTHY, Yousif, et al. Statins as antiepileptogenic drugs: Analyzing the evidence and identifying the most promising statin. Epilepsia, 2022, 63. Jg., Nr. 8, S. 1889-1898). Statins have been also reported to ameliorate symptoms in patients suffering from SARS-Cov2 infections and other severe diseases requiring intensive medical treatment (CASTIGLIONE, Vincenzo, et al. Statin therapy in CO VID-19 infection. European Heart Journal-Cardiovascular Pharmacotherapy, 2020, 6. Jg., Nr. 4, S. 258-259). As many of these patients suffer at least temporarily from reduced consciousness or may present with impaired gastroenteric motility, a parenteral atorvastatin formulation is of high medical interest.

[0027] There are currently no United States Food and Drug Administration (U.S. F.D.A.) approved parenteral or oral liquid pharmaceutical compositions of ATV (any salt). Furthermore, there are currently no U.S. F.D.A-approved liquid (parenteral or oral) pharmaceutical compositions combining ATV-Ca with any other pharmaceutical agents. Thus, there is a need for parenteral or oral liquid compositions including ATV or a pharmaceutically acceptable salt thereof for patients with limited ability to swallow tablets or capsules.

[0028] In certain aspects, provided is a pharmaceutical composition comprising atorvastatin, or a salt thereof, and a liquid carrier. The liquid carrier comprises ethylenediaminetetraacetic acid (EDTA), or a salt thereof. In some embodiments, at least a portion of the atorvastatin, or salt thereof, is dissolved within the liquid carrier.

[0029] In further aspects, provided is a pharmaceutical composition comprising atorvastatin, or a salt thereof, and a liquid carrier. The atorvastatin, or salt thereof, is dissolved within the liquid carrier at a concentration of at least 0.7 mg / mL. In certain embodiments, the liquid carrier comprises a chelating agent. In some embodiments, the chelating agent is selected from dimercaprol, penicillamine, trientine, deferasirox, deferiprone, deferoxamine, EDTA, or succimer, or a salt of any of the foregoing, or any combination thereof. In certain embodiments, the chelating agent is EDTA, or a salt thereof.

[0030] In certain embodiments, the atorvastatin, or salt thereof, is dissolved within the liquid carrier at a concentration of 0.7 mg / mL to 3.0 mg / mL. In some embodiments, the atorvastatin, or salt thereof, is dissolved within the liquid carrier at a concentration of 1.0 mg / mL to 2.5 mg / mL. In certain embodiments, the atorvastatin, or salt thereof, is dissolved within the liquid carrier at a concentration of about 2 mg / mL.

[0031] In some embodiments, the liquid carrier comprises 0.01% to 0.20% (w / w) EDTA, or a salt thereof. In certain embodiments, the liquid carrier comprises 0.05% to 0.10% (w / w) EDTA, or a salt thereof. In certain embodiments, the liquid carrier comprises about 0.07% (w / w) EDTA, or a salt thereof. In some embodiments, the EDTA or salt thereof is disodium EDTA or tetrasodium EDTA.

[0032] In certain embodiments, the atorvastatin or salt thereof is atorvastatin calcium.

[0033] In some embodiments, the liquid carrier comprises at least 70% (w / w) water. In certain embodiments, the liquid carrier comprises at least 75%, at least 80%, at least 85%, or at least 90% (w / w) water. In some embodiments, the liquid carrier comprises 70% to 99%, 75% to 99%, 80% to 99%, 85% to 99%, 85% to 98%, 90% to 98%, 93% to 98%, 92% to 97%, or 93 to 97% (w / w) water.

[0034] In certain embodiments, the liquid carrier comprises at least 70% (w / w) 10 millimolar phosphate in water. In certain embodiments, the liquid carrier comprises at least 75%, at least 80%, at least 85%, or at least 90% (w / w) 10 millimolar phosphate in water. In some embodiments, the liquid carrier comprises 70% to 99%, 75% to 99%, 80% to 99%, 85% to 99%, 85% to 98%, 90% to 98%, 93% to 98%, 92% to 97%, or 93 to 97% (w / w) 10 millimolar phosphate in water.

[0035] In certain embodiments, the liquid carrier comprises meglumine or a salt thereof. In some embodiments, the liquid carrier comprises 0.1% to 0.5% (w / w) meglumine or a salt thereof.

[0036] In certain embodiments, the liquid carrier comprises a surfactant. In some embodiments, the surfactant comprises polysorbate 80, polysorbate 20, a polyethylene glycol ester, a polyethylene glycol, a glycerol ether, a glyceryl monoleate, or lecithin. In certain embodiments, the surfactant comprises polysorbate 80. In some embodiments, the liquid carrier comprises about 1 % (w / w) polysorbate 80.

[0037] In certain embodiments, the liquid carrier does not comprise an antioxidant. In some embodiments, the liquid carrier does not comprise ascorbic acid, sodium metabisulfite, or potassium metabisulfite.

[0038] In some embodiments, the liquid carrier comprises propylene glycol. In certain embodiments, the liquid carrier comprises 1% to 10% (w / w) propylene glycol.

[0039] In some embodiments, the liquid carrier comprises a buffering agent. In certain embodiments, the buffering agent is acetic acid, citric acid, sodium citrate, sodium carbonate, sodium tetraborate, sodium phosphate, sodium acetate, meglumine or a salt thereof, sodium bicarbonate, or potassium phosphate, or a combination thereof. In certain embodiments, the buffering agent is sodium phosphate or potassium phosphate. In some embodiments, the composition has a pH of 6-10. In certain embodiments, the composition has a pH of about 8.

[0040] In certain embodiments, the osmolality of the composition is 200 to 3,000 Osmol / kg. In some embodiments, the osmolality of the composition is 300 to 700 Osmol / kg. In certain embodiments, the osmolality of the composition is about 500 Osmol / kg.

[0041] In some embodiments, the concentration of atorvastatin, or salt thereof, in the liquid carrier remains stable (e.g., does not decrease by more than 2%, 5%, 10%, or 20%) during storage. In certain embodiments, the concentration of the atorvastatin, or salt thereof, dissolved within the liquid carrier does not decrease by more than 5% after the composition is stored at 5°C for at least one week, at least two weeks, at least one month, at least two months, at least three months, at least six months, or at least one year. In certain embodiments, the concentration of the atorvastatin, or salt thereof, dissolved within the liquid carrier does not decrease by more than 5% after the composition is stored at 5°C for one week to one year, one week to six months, one week to three months, one week to two months, one week to one month, one week to two weeks, two weeks to one year, two weeks to six months, two weeks to three months, two weeks to two months, two weeks to one month, one month to one year, one month to six months, one month to three months, one month to two months, two months to one year, two months to six months, two months to three months, three months to one year, three months to six months, or six months to one year.

[0042] In certain embodiments, the concentration of the atorvastatin, or salt thereof, dissolved within the liquid carrier does not decrease by more than 5% after the composition is stored at 25 °C at least one week, at least two weeks, at least one month, at least two months, at least three months, at least six months, or at least one year. In certain embodiments, the concentration of the atorvastatin, or salt thereof, dissolved within the liquid carrier does not decrease by more than 5% after the composition is stored at 25°C for one week to one year, one week to six months, one week to three months, one week to two months, one week to one month, one week to two weeks, two weeks to one year, two weeks to six months, two weeks to three months, two weeks to two months, two weeks to one month, one month to one year, one month to six months, one month to three months, one month to two months, two months to one year, two months to six months, two months to three months, three months to one year, three months to six months, or six months to one year. In certain embodiments, the concentration of the atorvastatin, or salt thereof, dissolved within the liquid carrier does not decrease by more than 5% after the composition is stored at 50°C for at least one week, at least two weeks, at least one month, at least two months, at least three months, at least six months, or at least one year. In certain embodiments, the concentration of the atorvastatin, or salt thereof, dissolved within the liquid carrier does not decrease by more than 5% after the composition is stored at 50°C for one week to one year, one week to six months, one week to three months, one week to two months, one week to one month, one week to two weeks, two weeks to one year, two weeks to six months, two weeks to three months, two weeks to two months, two weeks to one month, one month to one year, one month to six months, one month to three months, one month to two months, two months to one year, two months to six months, two months to three months, three months to one year, three months to six months, or six months to one year.

[0043] In some embodiments, the purity of atorvastatin, or salt thereof, in the liquid carrier remains stable (e.g., remains at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, or at least 98%) during storage. In certain embodiments, the purity of the atorvastatin, or salt thereof, dissolved within the liquid carrier is at least 95% after the composition is stored at 5 °C and 100% relative humidity (RH) for at least one week, at least two weeks, at least one month, at least two months, at least three months, at least six months, or at least one year. In certain embodiments, the purity of the atorvastatin, or salt thereof, dissolved within the liquid carrier is at least 95% after the composition is stored at 5°C and 100% relative humidity (RH) for one week to one year, one week to six months, one week to three months, one week to two months, one week to one month, one week to two weeks, two weeks to one year, two weeks to six months, two weeks to three months, two weeks to two months, two weeks to one month, one month to one year, one month to six months, one month to three months, one month to two months, two months to one year, two months to six months, two months to three months, three months to one year, three months to six months, or six months to one year.

[0044] In certain embodiments, the purity of the atorvastatin, or salt thereof, dissolved within the liquid carrier is at least 95% after the composition is stored at 25 °C and 60% RH for at least one week, at least two weeks, at least one month, at least two months, at least three months, at least six months, or at least one year. In certain embodiments, the purity of the atorvastatin, or salt thereof, dissolved within the liquid carrier is at least 95% after the composition is stored at 25 °C and 60% RH for one week to one year, one week to six months, one week to three months, one week to two months, one week to one month, one week to two weeks, two weeks to one year, two weeks to six months, two weeks to three months, two weeks to two months, two weeks to one month, one month to one year, one month to six months, one month to three months, one month to two months, two months to one year, two months to six months, two months to three months, three months to one year, three months to six months, or six months to one year.

[0045] In certain embodiments, the purity of the atorvastatin, or salt thereof, dissolved within the liquid carrier is at least 95% after the composition is stored at 5 °C for at least one week, at least two weeks, at least one month, at least two months, at least three months, at least six months, or at least one year. In certain embodiments, the purity of the atorvastatin, or salt thereof, dissolved within the liquid carrier is at least 97% after the composition is stored at 5 °C for one week to one year, one week to six months, one week to three months, one week to two months, one week to one month, one week to two weeks, two weeks to one year, two weeks to six months, two weeks to three months, two weeks to two months, two weeks to one month, one month to one year, one month to six months, one month to three months, one month to two months, two months to one year, two months to six months, two months to three months, three months to one year, three months to six months, or six months to one year.

[0046] In certain embodiments, the purity of the atorvastatin, or salt thereof, dissolved within the liquid carrier is at least 95% after the composition is stored at 25 °C for at least one week, at least two weeks, at least one month, at least two months, at least three months, at least six months, or at least one year. In certain embodiments, the purity of the atorvastatin, or salt thereof, dissolved within the liquid carrier is at least 95% after the composition is stored at 25 °C for one week to one year, one week to six months, one week to three months, one week to two months, one week to one month, one week to two weeks, two weeks to one year, two weeks to six months, two weeks to three months, two weeks to two months, two weeks to one month, one month to one year, one month to six months, one month to three months, one month to two months, two months to one year, two months to six months, two months to three months, three months to one year, three months to six months, or six months to one year.

[0047] In some aspects, provided is a pharmaceutical composition comprising atorvastatin calcium and a liquid carrier. The atorvastatin calcium is dissolved within the liquid carrier at a concentration of about 2 mg / mL. The liquid carrier comprises: about 0.3% (w / w) meglumine or a salt thereof; about 3% (w / w) propylene glycol; about 1% (w / w) polysorbate 80; about 0.07% (w / w) tetrasodium EDTA; and 93% to 97% (w / w) 10 millimolar phosphate in water.

[0048] In some embodiments, the composition further comprises one or more additional therapeutic agents, i.e., one or more therapeutic agents in addition to the atorvastatin or salt thereof. In some embodiments, the one or more additional therapeutic agents is selected from levetiracetam, seletracetam, and brivaracetam, or a combination thereof. In certain embodiments, the one or more additional therapeutic agents is seletracetam. In some embodiments, the one or more additional therapeutic agents is levetiracetam. In some embodiments, the one or more additional therapeutic agents is selected from ceftriaxone, or a salt thereof, and clavulanic acid, or a salt thereof, or a combination thereof. In certain embodiments, the one or more additional therapeutic agents is a combination of: an SV2A agonist selected from the group consisting of levetiracetam, seletracetam, and brivaracetam, or a combination thereof; and an antibiotic selected from the group consisting of ceftriaxone, or a salt thereof, and clavulanic acid, or a salt thereof, or a combination thereof. In certain embodiments, the SV2A agonist is levetiracetam and the antibiotic is ceftriaxone, or a salt thereof. In some embodiments, the SV2A agonist is seletracetam and the antibiotic is ceftriaxone, or a salt thereof.

[0049] In some aspects, provided is a method of administering atorvastatin to a subject comprising administering a pharmaceutical composition comprising atorvastatin, or a salt thereof, to the subject parentally.

[0050] In certain aspects, provided is a method of administering a combination of atorvastatin, or a salt thereof, an SV2A agonist, and an antibiotic to a subject comprising parenterally administering to the subject a pharmaceutical composition comprising atorvastatin, or a salt thereof, an SV2A agonist, and an antibiotic. In certain embodiments, the SV2A agonist is selected from the group consisting of levetiracetam, seletracetam, and brivaracetam, or a combination thereof. In some embodiments, the antibiotic is selected from the group consisting of ceftriaxone, or a salt thereof, and clavulanic acid, or a salt thereof, or a combination thereof. In certain embodiments, the SV2A agonist is levetiracetam and the antibiotic is ceftriaxone, or a salt thereof. In some embodiments, the SV2A agonist is seletracetam and the antibiotic is ceftriaxone, or a salt thereof. In certain embodiments, the composition is administered intravenously. In some embodiments, the composition is administered subcutaneously. In certain embodiments, the composition is administered intramuscularly. In certain embodiments, the composition is administered intradermally, intrathecally, or intraperitoneally.

[0051] In some embodiments, the method comprises administering the composition according to embodiments described herein.

[0052] In certain aspects, provided is a method of administering atorvastatin to a subject comprising orally administering to the subject the composition according to embodiments described herein.

[0053] In certain embodiments, the subject suffers from dysphagia. In some embodiments, the subject suffers from oropharyngeal dysphagia, esophageal dysphagia, esophagogastric dysphagia, or paraesophageal dysphagia.

[0054] In some embodiments, the subject is in a state of reduced consciousness. In certain embodiments, the subject is unconscious. In some embodiments, the subject is in a coma.

[0055] In certain embodiments, the subject suffers from a gastric disorder. For subjects suffering from a gastric disorder, the administration of atorvastatin in a solid oral dosage form may be unpleasant.

[0056] In some aspects, provided is a method of treating a seizure disorder in a subject in need thereof comprising administering to the subject the composition according to embodiments described herein. In some embodiments, the seizure disorder comprises epilepsy, a first seizure, a febrile seizure, or eclampsia. In certain embodiments, the seizure disorder comprises epilepsy. In some embodiments, the epilepsy comprises absence epilepsy, frontal lobe epilepsy, temporal lobe epilepsy, neocortical epilepsy, juvenile myoclonic epilepsy, Lennox-Gastaut syndrome, infantile spasms, childhood absence epilepsy, Rasmussen’s encephalitis, Dravet syndrome, hypothalamic hamartoma, or developmental and epileptic encephalopathy. In certain embodiments, the subject is experiencing a seizure or a seizure cluster.

[0057] In certain aspects, provided is a method of treating dyslipidemia in a subject in need thereof comprising administering to the subject the composition according to embodiments described herein. In certain embodiments, the subject suffers from a heart disease (e.g., a coronary heat disease). In some embodiments, the subject has experienced a heart attack or a stroke. In certain embodiments, the subject has experienced a stroke. In some aspects, provided is a method of treating an infection in a subject in need thereof, comprising administering to the subject the composition according to embodiments described herein.

[0058] In certain aspects, provided is a method of treating epileptogenesis in a subject in need thereof, comprising administering to the subject the pharmaceutical composition according to embodiments described herein. In certain embodiments, the subject has experienced a traumatic brain injury.

[0059] In certain aspects, provided is a kit comprising a first container and a second container, wherein: the first container comprises atorvastatin, or a pharmaceutically acceptable salt thereof, and EDTA, or a pharmaceutically acceptable salt thereof; and the second container comprises a pharmaceutically acceptable solution comprising water and propylene glycol. In certain embodiments, the first container further comprises levetiracetam, seletracetam, or brivaracetam. In some embodiments, the first container further comprises ceftriaxone, or a salt thereof, or clavulanic acid, or a salt thereof. In certain embodiments, the second container further comprises meglumine or a salt thereof, polysorbate 80, and a buffering agent.

[0060] In some embodiments, the composition includes 0.1 mg / mL to 5 mg / mL (e.g., 1 mg / mL to 4 mg / mL, 1.5 mg / mL to 4 mg / mL, 20 mg / mL to 3 mg / mL, 2 mg / mL to 2.5 mg / mL, atorvastatin calcium.

[0061] In certain embodiments, the liquid carrier comprises meglumine or a salt thereof. In certain embodiments, the liquid carrier includes 1 mg / mL to 500 mg / mL (e.g., 1 mg / ml to 400 mg / ml, 1 mg / mL to 250 mg / ml, 1 mg / ml to 100 mg / mL, 1 mg / mL to 50 mg / mL, 5 mg / mL to 50 mg / mL, 10 mg / mL to 50 mg / mL, or 1 mg / mL to 30 mg / mL) of meglumine or a salt thereof.

[0062] In certain embodiments, the liquid carrier comprises EDTA, or a salt thereof. In certain embodiments, the liquid carrier includes 0.1 mg / mL to 10 mg / mL (e.g., 0.2 to 10 mg / ml, 0.2 mg / mL to 4 mg / mL, 0.2 mg / mL to 2 mg / mL, 0.5 mg / mL 10 mg / ml, 0.5 to 4 mg / ml, 0.5 to 2 mg / mL, 0.5 mg / mL to 1.5 mg / mL, 1 mg / ml to 10 mg / ml, 1 mg / ml to 5 mg / ml, 1 mg / ml to 2.5 mg / ml, 2 mg / ml to 10 mg / ml, 2 mg / ml to 5 mg / ml, 2 mg / ml to 2.5 mg / ml, 4 mg / ml to 10 mg / ml) EDTA or a salt thereof. In some embodiments, the EDTA or salt thereof is tetrasodium EDTA or disodium EDTA.

[0063] In certain embodiments, the liquid carrier comprises propylene glycol. In certain embodiments, the liquid carrier comprises 1 mg / mL to 500 mg / mL (e.g., 10 mg / mL to 250 mg / mL, 10 mg / mL to 150 mg / mL, 30 mg / mL to 150 mg / mL, 50 mg / mL to 150 mg / mL, or 50 mg / mL to 100 mg / mL) of propylene glycol.

[0064] In certain embodiments, the liquid carrier comprises polyethylene glycol (e.g., PEG400). In some embodiments, as the liquid carrier comprises PEG200, PEG 300, or EPG800. In certain embodiments, the liquid carrier includes 1 mg / mL to 500 mg / mL (e.g., 10 mg / mL to 250 mg / mL, 10 mg / mL to 150 mg / mL, 30 mg / mL to 150 mg / mL, 50 mg / mL to 150 mg / mL, or 50 mg / mL to 100 mg / mL) of polyethylene glycol.

[0065] In certain embodiments, the liquid carrier comprises a combination of polyethylene glycol and propylene glycol at a ratio of 0.1 : 100 to 100:0.1 (weight by weight). In certain embodiments, the liquid carrier includes 1 mg / mL to 500 mg / mL (e.g., 10 mg / mL to 250 mg / mL, 10 mg / mL to 150 mg / mL, 30 mg / mL to 150 mg / mL, 50 mg / mL to 150 mg / mL, or 50 mg / mL to 100 mg / mL) of the combination of polyethylene glycol with propylene glycol.

[0066] In certain embodiments, the liquid carrier comprises polyoxyethylene (20) sorbitan monooleate (polysorbate 80). In certain embodiments, the liquid carrier includes 1 mg / mL to 50 mg / mL (e.g., 1 mg / mL to 25 mg / mL, 1 mg / mL to 15 mg / mL, 3 mg / mL to 15 mg / mL, 5 mg / mL to 15 mg / mL, or 5 mg / mL to 10 mg / mL) of polysorbate 80.

[0067] In certain embodiments, the liquid carrier comprises propylene glycol or polyethylene glycol or combinations of both, and polysorbate 80. In certain embodiments, the composition includes 10 mg / mL to 500 mg / mL (e.g., 10 mg / mL to 250 mg / mL, 10 mg / mL to 150 mg / mL, 30 mg / mL to 150 mg / mL, 50 mg / mL to 150 mg / mL, or 50 mg / mL to 100 mg / mL) of polyethylene glycol or propylene glycol, combined with 1 mg / mL to 50 mg / mL (e.g., 1 mg / mL to 25 mg / mL, 1 mg / mL to 15 mg / mL, 3 mg / mL to 15 mg / mL, 5 mg / mL to 15 mg / mL, or 5 mg / mL to 10 mg / mL) of polysorbate 80.

[0068] In certain embodiments, the composition comprises levetiracetam. In particular embodiments, the composition includes 5 mg / mL to 500 mg / mL (e.g., 5 mg / mL to 150 mg / mL, 20 mg / mL to 150 mg / mL, 60 mg / mL to 120 mg / mL, or 30 mg / mL to 60 mg / mL) of levetiracetam. In further embodiments, the weight ratio of levetiracetam to atorvastatin or salt thereof (e.g., atorvastatin calcium) to is 200: 1 or less (e.g., 100: 1 or less) in the composition. In yet further embodiments, the weight ratio of levetiracetam to atorvastatin or salt thereof (e.g., atorvastatin calcium) is at least 10: 1 in the composition. In certain embodiments, the composition comprises brivaracetam. In still further embodiments, the composition includes 0.5 mg / mL to 50 mg / mL (e.g., 2 mg / mL to 8 mg / mL, 4 mg / mL to 8 mg / mL, or 2 mg / mL to 4 mg / mL) of brivaracetam. In some embodiments, the weight ratio of brivaracetam to atorvastatin or salt thereof (e.g., atorvastatin calcium)is 4: 1 or less in the composition. In certain embodiments, the weight ratio of brivaracetam to atorvastatin or salt thereof (e.g., atorvastatin calcium) is at least 1: 1 in the composition.

[0069] In certain embodiments, the solution comprises seletracetam. In some embodiments, the composition includes 0.25 mg / mL to 50 mg / mL (e.g., 1 mg / mL to 8 mg / mL, 2 mg / ml to 8 mg / ml, 4 mg / mL to 8 mg / mL, or 2 mg / mL to 4 mg / mL) of seletracetam. In certain embodiments, the weight ratio of seletracetam to atorvastatin or salt thereof (e.g., atorvastatin calcium)is 4: 1 or less in the composition. In some embodiments, the weight ratio of seletracetam to atorvastatin or salt thereof (e.g., atorvastatin calcium) is at least 0.5: 1 in the composition.

[0070] In certain embodiments, the composition comprises ceftriaxone or a pharmaceutically acceptable salt thereof. In some embodiments, the composition comprises 5 mg / mL to 500 mg / mL (e.g., 5 mg / mL to 150 mg / mL, 20 mg / mL to 150 mg / mL, 60 mg / mL to 120 mg / mL, or 30 mg / mL to 60 mg / mL) of ceftriaxone. In further embodiments, the weight ratio of ceftriaxone to atorvastatin or salt thereof (e.g., atorvastatin calcium) is 200: 1 or less (e.g., 150: 1 or less, or 100: 1 or less) in the composition. In yet further embodiments, the weight ratio of ceftriaxone to atorvastatin or salt thereof (e.g., atorvastatin calcium) is at least 10:1 in the composition.

[0071] In certain embodiments, the composition comprises clavulanic acid or a pharmaceutically acceptable salt thereof, i.e. clavulanate.

[0072] In some embodiments, the composition comprises 5 mg / mL to 500 mg / mL (e.g., 5 mg / mL to 150 mg / mL, 20 mg / mL to 150 mg / mL, 60 mg / mL to 120 mg / mL, or 30 mg / mL to 60 mg / mL) of clavulanate. In further embodiments, the weight ratio of clavulanate to atorvastatin or salt thereof (e.g., atorvastatin calcium) is 200:1 or less (e.g., 150:1 or less, or 100: 1 or less) in the composition. In yet further embodiments, the weight ratio of clavulanate to atorvastatin or salt thereof (e.g., atorvastatin calcium)is at least 10: 1 in the composition.

[0073] In certain embodiments, the composition further includes an acidulant (e.g., acetic acid, hydrochloric acid).

[0074] In certain embodiments, the composition has a pH of 6.5 to 10.0 (e.g., 7.5 to 9.5). In some embodiments, the composition is formulated for parenteral administration (e.g., for intravenous administration, subcutaneous administration, or intramuscular administration). In certain embodiments, the composition is formulated for oral administration.

[0075] In another aspect, provided are kits including a first container and a second container. The first container comprises atorvastatin or salt thereof (e.g., atorvastatin calcium). The second container comprises a pharmaceutically acceptable solution of meglumine or a salt thereof and other pharmaceutical excipients, e.g. disodium- or tetrasodium EDTA, polysorbate 80, and propylene glycol or polyethylene glycol.

[0076] In some embodiments, the combination of the contents of the first container and the second container produces the composition according to embodiments described herein.

[0077] In some embodiments, atorvastatin or salt thereof (e.g., atorvastatin calcium) is present in the first container in a crystalline, micronized or lyophilized form. In certain embodiments, the atorvastatin or salt thereof (e.g., atorvastatin calcium) is present in an amount sufficient to produce a composition including 0.1 mg / mL to 5 mg / mL of atorvastatin or salt thereof (e.g., atorvastatin calcium) upon combination with the solution of the second container.

[0078] In certain embodiments, the solution includes 1 mg / mL to 250 mg / mL of meglumine or a salt thereof.

[0079] In further embodiments, the solution includes 0.1 mg / mL to 10 mg / mL EDTA or a salt thereof (e.g., tetrasodium EDTA or disodium-EDTA).

[0080] In further embodiments, the solution includes 10 mg / mL to 500 mg / mL propylene glycol or polyethylene glycol or combinations of both at a ratio of 0.1 : 100 to 100:0.1.

[0081] In further embodiments, the solution includes 1 mg / mL to 50 mg / mL polysorbate 80.

[0082] In further embodiments, the first container further includes levetiracetam. In yet further embodiments, levetiracetam is present in an amount sufficient to produce a composition including 5 mg / mL to 500 mg / mL of levetiracetam upon combination with the solution of the second container. In still further embodiments, the weight ratio of levetiracetam to atorvastatin or salt thereof (e.g., atorvastatin calcium) is 200:1 or less (e.g., 100:1 or less). In other embodiments, the weight ratio of levetiracetam to atorvastatin or salt thereof (e.g., atorvastatin calcium) is at least 10: 1.

[0083] In further embodiments, the first container further includes brivaracetam or seletracetam.

[0084] In still further embodiments, brivaracetam or seletracetam is present in an amount sufficient to produce a composition including 0.5 mg / mL to 50 mg / mL of brivaracetam or seletracetam upon combination with the solution of the 2ndcontainer. In still further embodiments, the weight ratio, the weight ratio of brivaracetam to atorvastatin or salt thereof (e.g., atorvastatin calcium) is 4:1 or less. In certain embodiments, the weight ratio of brivaracetam to atorvastatin or salt thereof (e.g., atorvastatin calcium) is at least 1:1. In still further embodiments, the weight ratio, the weight ratio of seletracetam to atorvastatin or salt thereof (e.g., atorvastatin calcium) is 4: 1 or less. In some embodiments, the weight ratio of seletracetam to atorvastatin or salt thereof (e.g., atorvastatin calcium) is at least 0.5: 1.

[0085] In certain embodiments, the first container further includes ceftriaxone or a pharmaceutically acceptable salt thereof. In some embodiments, ceftriaxone is present in an amount sufficient to produce a composition including 5 mg / mL to 500 mg / mL of levetiracetam upon combination with the solution of the second container. In certain embodiments, the weight ratio of ceftriaxone to atorvastatin or salt thereof (e.g., atorvastatin calcium) to is 200: 1 or less (e.g., 100: 1 or less). In some embodiments, the weight ratio of levetiracetam to atorvastatin or salt thereof (e.g., atorvastatin calcium) is at least 10: 1.

[0086] In certain embodiments, the first container contents and the second container contents upon combination produce a composition having a pH of 6.5 to 10.0 (e.g., 7.5 to 9.5).

[0087] In some embodiments, the kit further includes an acidulant (e.g., acetic acid or hydrochloric acid). In still further embodiments, the solution of the second container includes the acidulant.

[0088] In some embodiments, combination of the first container contents and the second container contents produces a composition for parenteral administration. In certain embodiments, combination of the first container contents and the second container contents produces a composition for intravenous administration, subcutaneous administration, or intramuscular administration. In some embodiments, combination of the first container contents and the second container contents produces a composition for oral administration. In certain embodiments, combination of the first container contents and the second container contents produces a dosage form.

[0089] In some embodiments, the first container contents are solid (e.g., micronized or lyophilized). In certain aspects, disclosed are methods of treating a subject in need thereof by administering to the subject a therapeutically effective amount of the composition according to embodiments described herein.

[0090] In some aspects, disclosed are methods of treating a subject in need thereof by combining the first container contents and the second container contents in the kit according to embodiments described herein to produce a pharmaceutical composition comprising atorvastatin or a salt thereof dissolved within a liquid carrier, and administering a therapeutically effective amount of the pharmaceutical composition to the patient.

[0091] In some embodiments, the therapeutically effective amount is an amount providing 0.1 mg / kg / day to 2.5 mg / kg / day (e.g., 0.2 mg / kg / day to 2.0 mg / kg / day) of atorvastatin or salt thereof (e.g., atorvastatin calcium). In certain embodiments, the therapeutically effective amount is an amount providing at least 5 mg / day (e.g., at least 10 mg / day) of atorvastatin or salt thereof (e.g., atorvastatin calcium). In some embodiments, the therapeutically effective amount is an amount providing 200 mg / day or less (e.g., 100 mg / day or less) of atorvastatin or salt thereof (e.g., atorvastatin calcium).

[0092] In further embodiments, the therapeutically effective amount is an amount providing 2.5 mg / kg / day to 150 mg / kg / day (e.g., 10 mg / kg / day to 75 mg / kg / day) of levetiracetam.

[0093] In further embodiments, the therapeutically effective amount is an amount providing 0.2 mg / kg / day to 10 mg / kg / day (e.g., 0.5 mg / kg / day to 5 mg / kg / day) of brivaracetam.

[0094] In further embodiments, the therapeutically effective amount is an amount providing 012 mg / kg / day to 10 mg / kg / day (e.g., 0.25 mg / kg / day to 5 mg / kg / day) of seletracetam.

[0095] In further embodiments, the therapeutically effective amount is an amount providing 2.5 mg / kg / day to 150 mg / kg / day (e.g., 10 mg / kg / day to 75 mg / kg / day) of ceftriaxone.

[0096] In some embodiments, the composition is administered parenterally (e.g., intravenously, subcutaneously, or intramuscularly). In yet other embodiments, the composition is administered orally.

[0097] In some embodiments, the subject is in need of a treatment with atorvastatin for a disorder or condition selected from dyslipidemia (for reduction of elevated total cholesterol (total-C), LDL-cholesterol (LDL-C), apolipoprotein B, and triglycerides), cardiac events (cardiac stroke, myocardial infarction) and cerebral stroke. In certain embodiments, the subject is in need of preventive treatment with ATV due to a high risk for a first cardiovascular event.

[0098] In some embodiments, the subject has suffered either a cardiovascular event (e.g., a stroke or myocardial infarction) or has suffered a cerebral stroke or cerebra hemorrhagic infarct and is therefore in need of a treatment with atorvastatin or salt thereof (e.g., atorvastatin calcium) to limit the damage induced by the event and to increase the likelihood of survival and recovery.

[0099] In certain embodiments, the subject is unable to swallow oral medication, due to, e.g., reduced consciousness or swallowing disorder, or due to gastrointestinal conditions prohibiting oral intake of medication such as, e.g., planned gastrointestinal surgery or severe nausea, and thus cannot continue the oral medication with atorvastatin or salt thereof (e.g., atorvastatin calcium).

[0100] In some embodiments, the subject is in need of a treatment for a disorder or condition selected from the group consisting of epilepsy, seizures, anoxia, stroke, traumatic brain injury, brain infection, brain abscess, aneurism, subarachnoid hemorrhage, status epilepticus, refractory status epilepticus, refractory partial onset seizures (POS), gambling addiction, migraines, substance dependence, alcoholism, cocaine dependence, nicotine dependence, metabolic syndrome X, diabetes mellitus, type 2, vomiting, obsessive-compulsive disorder, refractory generalized social phobia, Tourette Syndrome, levodopa-induced dyskinesia in Parkinson’s Disease, Prader-Willi syndrome, multiple sclerosis, Lennox-Gastaut Syndrome, Dravet’s syndrome, bipolar disorder, obesity, post-traumatic stress disorder, cluster headaches, severe headaches, and conditions caused by exposure to a chemical warfare nerve agent.

[0101] In some embodiments, the subject is in need of neuroprotection. In certain embodiments, the subject is in need of a treatment for a disorder or condition selected from the group consisting of traumatic brain injury, stroke, a brain infection and subarachnoid hemorrhage. In certain embodiments, the subject is in need of a treatment for traumatic brain injury. In some embodiments, the patient is in need of a treatment for stroke. In certain embodiments, the patient is in need of a treatment for a brain infection. In certain embodiments, the patient is in need of a treatment for encephalitis, meningoencephalitis or a brain abscess.

[0102] Atorvastatin In certain embodiments, the pharmaceutical composition comprises, e.g., 0.1 mg / mL to 6 mg / mL (e.g., 0.1 mg / mL to 6 mg / mL, 0.4 mg / mL to 6 mg / mL, 1 mg / mL to 6 mg / mL, 1.5 mg / mL to 6 mg / mL, 2 mg / mL to 6 mg / mL, 2.5 mg / mL to 6 mg / mL, 3 mg / mL to 6 mg / mL, 4 mg / mL to 6 mg / mL, 5 mg / ml to 6 mg / ml, 0.1 mg / mL to 4 mg / mL, 0.4 mg / mL to 4 mg / mL, 1 mg / mL to 4 mg / mL, 1.5 mg / mL to 4 mg / mL, 2 mg / mL to 4 mg / mL, 2.5 mg / mL to 4 mg / mL, 3 mg / mL to 4 mg / mL, 0.1 mg / mL to 3 mg / mL, 0.4 mg / mL to 3 mg / mL, 1 mg / mL to 3 mg / mL, 1.5 mg / mL to 3 mg / mL, 2 mg / mL to 3 mg / mL, 2.5 mg / mL to 3 mg / mL, 0.1 mg / mL to 2.5 mg / mL, 0.4 mg / mL to 2.5 mg / mL, 1 mg / mL to 2.5 mg / mL, 1.5 mg / mL to 2.5 mg / mL, 2 mg / mL to 2.5 mg / mL, 0.1 mg / mL to 2.5 mg / mL, 0.4 mg / mL to 2.5 mg / mL, 1.0 mg / mL to 2.5 mg / mL, 1.5 mg / mL to 2.5 mg / mL, 2.0 mg / mL to 2.5 mg / mL, 0.1 mg / mL to 2.0 mg / mL, 0.4 mg / mL to 2.0 mg / mL, 1.0 mg / mL to 2.0 mg / mL, 1.5 mg / mL to 2.0 mg / mL, 0.1 mg / mL to 1.5 mg / mL,0.4 mg / mL to 1.5 mg / mL, 1.0 mg / mL to 1.5 mg / mL) of atorvastatin or salt thereof (e.g., atorvastatin calcium).

[0103] In certain embodiments, the composition comprises 1.0 mg / mL to 4.0 mg / mL (e.g., 1.3 mg / mL to 4.0 mg / mL, 1.5 mg / mL to 4.0 mg / mL, 2.0 mg / mL to 4.0 mg / mL, 2.5 mg / mL to 4.0 mg / mL, 3.0 mg / ml to 4.0 mg / ml, 3.5 mg / ml to 4.0 mg / ml, 1.0 mg / mL to 3.0 mg / mL, 1.3 mg / mL to 3.0 mg / mL, 1.5 mg / mL to 3.0 mg / mL, 2.0 mg / mL to 3.0 mg / mL, 2.5 mg / mL to 3.0 mg / mL, 1.0 mg / mL to 2.5 mg / mL, 1.3 mg / mL to 2.5 mg / mL, 1.5 mg / mL to 2.5 mg / mL, 2.0 mg / mL to 2.5 mg / mL, 1.0 mg / mL to 2.0 mg / mL, 1.3 mg / mL to 2.0 mg / mL, 1.5 mg / mL to 2.0 mg / mL, 1.0 mg / mL to 1.5 mg / mL,) of atorvastatin or salt thereof (e.g., atorvastatin calcium).

[0104] In some embodiments, the composition comprises 1.5 mg / mL to 4.0 mg / mL (e.g., 1.5 mg / mL to 3.5 mg / mL, 1.7 mg / mL to 3.5 mg / mL, 2.0 mg / mL to 3.5 mg / mL, 2.5 mg / mL to 3.5 mg / mL, 3.0 mg / mL to 3.5 mg / mL, 1.5 mg / mL to 3.0 mg / mL, 1.7 mg / mL to 3.0 mg / mL, 2.0 mg / mL to 3.0 mg / mL, 2.5 mg / mL to 3.0 mg / mL, 1.5 mg / mL to 2.5 mg / mL, 1.7 mg / mL to 2.5 mg / mL, 2.0 mg / mL to 2.5 mg / mL,) of atorvastatin or salt thereof (e.g., atorvastatin calcium).

[0105] In certain embodiments, the composition comprises at least 0.5 mg / mL, at least 0.6 mg / mL, at least 0.7 mg / mL, at least 0.8 mg / mL, at least 0.9 mg / mL, at least 1 mg / mL, at least 1.2 mg / mL, or at least 1.5 mg / mL of atorvastatin or salt thereof (e.g., atorvastatin calcium). In some embodiments, the composition comprises at least 0.7 mg / mL of atorvastatin or salt thereof (e.g., atorvastatin calcium). In certain embodiments, the composition comprises 1.0 mg / mL to 2.5 mg / mL atorvastatin or salt thereof (e.g., atorvastatin calcium). In some embodiments, the solution comprises about 2.0 mg / mL atorvastatin or salt thereof (e.g., atorvastatin calcium). In some preferred embodiments (e.g., in instances where a lower concentration of solvents and co-solvents is preferable, such as in liquid pharmaceutical compositions containing a combination of therapeutic agents described herein or in formulations for newborn or children or elderly), the composition includes 0.1 mg / mL to 2.0 mg / mL (e.g., 0.4 mg / mL to 2.0 mg / mL, 1.0 mg / mL to 2.0 mg / mL, 1.5 mg / mL to 2.0 mg / mL, 0.4 mg / mL to 1.5 mg / mL, 1.0 mg / mL to 1.5 mg / mL, 0.4 mg / mL to 1.0 mg / mL) of atorvastatin or salt thereof (e.g., atorvastatin calcium). In certain more preferred embodiments (e.g., in instances where a lower concentration solvents and co-solvents (e.g., 1 mg / mL to 50 mg / mL (preferably, 5 mg / mL to 50 mg / mL) propylene glycol or 1 mg / ml to 50 mg / ml (preferably, 5 mg / mL to 50 mg / mL) polyethylene glycol or mixtures of propylene glycol and polyethylene glycol, 1: 100 to 100:1, at a combined concentration of 1 mg / ml to 50 mg / ml (preferably, 5 mg / mL to 50 mg / mL), and polysorbate 80, 0.1 mg / ml to 0.5 mg / ml), the composition includes 0.1 mg / mL to 1.5 mg / mL (e.g., 0.4 mg / mL to 1.5 mg / mL, 0.6 mg / mL to 1.5 mg / mL, 1.0 mg / mL to 1.5 mg / mL) of atorvastatin or salt thereof (e.g., atorvastatin calcium). In even more preferred embodiments (e.g., in instances where a lower concentration of solvents and co-solvents is preferable, meglumine and propylene glycol, polyethylene glycol and polysorbate 80 are omitted from the formulation and only EDTA or a salt thereof is used at a concentration of 0.1 mg / mL to 10 mg / mL (e.g., 0.2 to 10 mg / ml, 0.2 mg / mL to 4 mg / mL, 0.2 mg / mL to 2 mg / mL, 0.5 mg / mL 10 mg / ml, 0.5 to 4 mg / ml, 0.5 to 2 mg / mL, 0.5 mg / mL to 1.5 mg / mL, 1 mg / ml to 10 mg / ml, 1 mg / ml to 5 mg / ml, 1 mg / ml to 2.5 mg / ml, 2 mg / ml to 10 mg / ml, 2 mg / ml to 5 mg / ml, 2 mg / ml to 2.5 mg / ml, 4 mg / ml to 10 mg / ml). In such preparations, the concentration of atorvastatin or salt thereof (e.g., atorvastatin calcium) is 0.1 mg / mL to 1.5 mg / mL (e.g., 0.4 mg / mL to 1.5 mg / mL, 0.6 mg / mL to 1.5 mg / mL, 1.0 mg / mL to 1.5 mg / mL).

[0106] Still more preferably, the composition includes 0.4 mg / mL to 2 mg / mL (e.g., 0.4 mg / mL to 1.6 mg / mL, 0.4 mg / mL to 1 mg / mL, 0.4 mg / mL to 0.8 mg / mL, 0.4 mg / mL to 0.5 mg / mL, 0.5 mg / mL to 2 mg / mL, 0.5 mg / mL to 1.6 mg / mL, 0.5 mg / mL to 1 mg / mL, 0.5 mg / mL to 0.8 mg / mL, 1 mg / mL to 2 mg / mL, 1 mg / mL to 1.6 mg / mL, or 1.6 mg / mL to 2 mg / mL) of atorvastatin or salt thereof (e.g., atorvastatin calcium). In some particularly preferred embodiments, the composition includes 1.2 mg / mL to 2.0 mg / mL atorvastatin or salt thereof (e.g., atorvastatin calcium). In alternative particularly preferred embodiments (e.g., for pharmaceutical compositions configured for administration at a higher dosage volume (e.g., 40 mL to 50 mL)), the composition includes 0.5 mg / mL to 1.0 mg / mL of atorvastatin or salt thereof (e.g., atorvastatin calcium).

[0107] EDTA

[0108] In certain embodiments, the liquid carrier comprises EDTA or a salt thereof. In some embodiments, the liquid carrier comprises 0.01% to 0.20% (w / w) EDTA, or a salt thereof. In certain embodiments, the liquid carrier comprises 0.02% to 0.18% (w / w), 0.03% to 0.15% (w / w), 0.05% to 0.10% (w / w), or about 0.07% (w / w) EDTA or a salt thereof. In certain embodiments, the EDTA or salt thereof is disodium EDTA or tetrasodium EDTA.

[0109] In some embodiments, the liquid carrier comprises 0.1 mg / mL to 50 mg / mL (e.g., 0.1 mg / mL to 45 mg / mL, 0.1 mg / mL to 40 mg / mL, 0.1 mg / ml to 30 mg / mL, 0.1 mg / ml to 25 mg / mL, 0.1 mg / mL to 20 mg / mL, 0.1 mg / mL to 15 mg / mL, 0.1 mg / mL to 10 mg / mL, 0.1 mg / mL to 7.5 mg / ml, 0.1 mg / mL to 6 mg / mL, 0.1 mg / mL to 5 mg / mL, 0.1 mg / mL to 3 mg / mL, 0.1 mg / mL to 2.5 mg / mL, 0.1 mg / mL to 1 mg / mL, 0.5 mg / mL to 45 mg / mL, 0.5 mg / mL to 40 mg / mL, 0.5 mg / mL to 30 mg / mL, 0.5 mg / mL to 25 mg / mL, 0.5 mg / mL to 20 mg / mL, 0.5 mg / mL to 15 mg / mL, 0.5 mg / mL to 10 mg / mL, 0.5 mg / mL to 7.5 mg / mL, 0.5 mg / mL to 6 mg / mL, 0.5 mg / mL to 5 mg / mL, 0.5 mg / mL to 3 mg / mL, 0.5 mg / mL to 2.5 mg / mL, 0.5 mg / mL to 1 mg / mL, 0.7 mg / mL to 45 mg / mL, 0.7 mg / mL to 40 mg / mL, 0.7 mg / mL to 30 mg / mL, 0.7mg / mL to 25 mg / mL, 0.7 mg / mL to 20 mg / mL, 0.7 mg / mL to 15 mg / mL, 0.7 mg / mL to 10 mg / mL, 0.7 mg / mL to 7.5 mg / mL, 0.7 mg / mL to 6 mg / mL, 0.7 mg / mL to 5 mg / mL, 0.7 mg / mL to 3 mg / mL, 0.7 mg / mL to 2.5 mg / mL, 0.7 mg / mL to 1 mg / mL, 1 mg / mL to 45 mg / mL, 1 mg / mL to 40 mg / mL, 1 mg / mL to 30 mg / mL, 1 mg / mL to 25 mg / mL, 1 mg / mL to 20 mg / mL, 1 mg / mL to 15 mg / mL, 1 mg / mL to 10 mg / mL, 1 mg / mL to 7.5 mg / mL, 1 mg / mL to 6 mg / mL, 1 mg / mL to 5 mg / mL, 1 mg / mL to 3 mg / mL, 1 mg / mL to 2.5 mg / mL, 2.5 mg / mL to 45 mg / mL, 2.5 mg / mL to 40 mg / mL, 2.5 mg / mL to 30 mg / mL, 2.5 mg / mL to 25 mg / mL, 2.5 mg / mL to 20 mg / mL, 2.5 mg / mL to 15 mg / mL, 2.5 mg / mL to 10 mg / mL, 2.5 mg / mL to 7.5 mg / mL, 2.5 mg / mL to 6 mg / mL, 2.5 mg / mL to 5 mg / mL, 2.5 mg / mL to 3 mg / mL, 5 mg / mL to 45 mg / mL, 5 mg / mL to 40 mg / mL, 5 mg / mL to 30 mg / mL, 5 mg / mL to 25 mg / mL, 5 mg / mL to 20 mg / mL, 5 mg / mL to 15 mg / mL, 5 mg / mL to 10 mg / mL, 5 mg / mL to 7.5 mg / mL, 5 mg / mL to 6 mg / mL, 6 mg / mL to 45 mg / mL, 6 mg / mL to 40 mg / mL, 6 mg / mL to 30 mg / mL, 6 mg / mL to 25 mg / mL, 6 mg / mL to 20 mg / mL, 6 mg / mL to 15 mg / mL, 6 mg / mL to 10 mg / mL, 6 mg / mL to 7.5 mg / mL, 7.5 mg / mL to 45 mg / mL, 7.5 mg / mL to 40 mg / mL, 7.5 mg / mL to 30 mg / mL, 7.5 mg / mL to 25 mg / mL, 7.5 mg / mL to 20 mg / mL, 7.5 mg / mL to 15 mg / mL, 7.5 mg / mL to 10 mg / mL, 10 mg / mL to 45 mg / mL, 10 mg / mL to 40 mg / mL, 10 mg / mL to 30 mg / mL, 10 mg / mL to 25 mg / mL, 10 mg / mL to 20 mg / mL, 10 mg / mL to 15 mg / mL, 15 mg / mL to 45 mg / mL, 15 mg / mL to 40 mg / mL, 150 mg / mL to 30 mg / mL, 15 mg / mL to 25 mg / mL, 15 mg / mL to 20 mg / mL, 20 mg / mL to 45 mg / mL, 20 mg / mL to 40 mg / mL, 20 mg / mL to 30 mg / mL, 20 mg / mL to 25 mg / mL, 25 mg / mL to 45 mg / mL, 25 mg / mL to 40 mg / mL, 25 mg / mL to 30 mg / mL, 30 mg / mL to 45 mg / mL, 30 mg / mL to 40 mg / mL, 40 mg / mL to 45 mg / mL) of EDTA or a salt thereof (e.g., tetrasodium EDTA or disodium EDTA).

[0110] In certain embodiments, the liquid carrier comprises 0.1 mg / mL to 10 mg / mL (e.g., 0.1 mg / mL to 9 mg / mL, 0.1 mg / mL to 8 mg / mL, 0.1 mg / mL to 7 mg / mL, 0.1 mg / mL to 6 mg / mL, 0.1 mg / mL to 5 mg / mL, 0.1 mg / mL to 4 mg / mL, 0.1 mg / mL to 3 mg / mL, 0.1 mg / mL to 2.5 mg / mL, 0.1 mg / mL to 2 mg / mL, 0.1 mg / mL to 1.5 mg / mL, 0.1 mg / mL to 1 mg / mL, 0.1 mg / mL to 0.7 mg / mL, 0.1 mg / mL to 0.5 mg / mL, 0.2 mg / mL to 10 mg / mL, 0.2 mg / mL to 9 mg / mL, 0.2 mg / mL to 8 mg / mL, 0.2 mg / mL to 7 mg / mL, 0.2 mg / mL to 6 mg / mL, 0.2 mg / mL to 5 mg / mL, 0.2 mg / mL to 4 mg / mL, 0.2 mg / mL to 3 mg / mL, 0.2 mg / mL to 2.5 mg / mL, 0.2 mg / mL to 2 mg / mL, 0.2 mg / mL to 1.5 mg / mL, 0.2 mg / mL to 1 mg / mL, 0.2 mg / mL to 0.7 mg / mL, 0.2 mg / mL to 0.5 mg / mL, 03 mg / mL to 10 mg / mL, 0.3 mg / mL to 9 mg / mL, 0.3 mg / mL to 8 mg / mL, 0.3 mg / mL to 7 mg / mL, 0.3 mg / mL to 6 mg / mL, 0.3 mg / mL to 5 mg / mL, 0.3 mg / mL to 4 mg / mL, 0.3 mg / mL to 3 mg / mL, 0.3 mg / mL to 2.5 mg / mL, 0.3 mg / mL to 2 mg / mL, 0.3 mg / mL to 1.5 mg / mL, 0.3 mg / mL to 1 mg / mL, 0.3 mg / mL to 0.7 mg / mL, 0.3 mg / mL to 0.5 mg / mL, 0.4 mg / mL to 10 mg / mL, 0.4 mg / mL to 9 mg / mL, 0.4 mg / mL to 8 mg / mL, 0.4 mg / mL to 7 mg / mL, 0.4 mg / mL to 6 mg / mL, 0.4 mg / mL to 5 mg / mL, 0.4 mg / mL to 4 mg / mL, 0.4 mg / mL to 3 mg / mL, 0.4 mg / mL to 2.5 mg / mL, 0.4 mg / mL to 2 mg / mL, 0.4 mg / mL to 1.5 mg / mL, 0.4 mg / mL to 1 mg / mL, 0.4 mg / mL to 0.7 mg / mL, 04 mg / mL to 0.5 mg / mL, 0.5 mg / mL to 10 mg / mL, 0.5 mg / mL to 9 mg / mL, 0.5 mg / mL to 8 mg / mL, 0.5 mg / mL to 7 mg / mL, 0.5 mg / mL to 6 mg / mL, 0.5 mg / mL to 5 mg / mL, 0.5 mg / mL to 4 mg / mL, 0.5 mg / mL to 3 mg / mL, 0.5 mg / mL to 2.5 mg / mL, 0.5 mg / mL to 2 mg / mL, 0.5 mg / mL to 1.5 mg / mL, 0.5 mg / mL to 1 mg / mL, 0.5 mg / mL to 0.7 mg / mL, 1 mg / mL to 10 mg / mL, 1 mg / mL to 9 mg / mL, 1 mg / mL to 8 mg / mL, 1 mg / mL to 7 mg / mL, 1 mg / mL to 6 mg / mL, 1 mg / mL to 5 mg / mL, 1 mg / mL to 4 mg / mL, 1 mg / mL to 3 mg / mL, 1 mg / mL to 2.5 mg / mL, 1 mg / mL to 2 mg / mL, 1 mg / mL to 1.5 mg / mL, 1.5 mg / mL to 10 mg / mL, 1.5 mg / mL to 9 mg / mL, 1.5 mg / mL to 8 mg / mL, 1.5 mg / mL to 7 mg / mL,

[0111] 1.5 mg / mL to 6 mg / mL, 1.5 mg / mL to 5 mg / mL, 1.5 mg / mL to 4 mg / mL, 1.5 mg / mL to 3 mg / mL, 1.5 mg / mL to 2.5 mg / mL, 1.5 mg / mL to 2 mg / mL, 2 mg / mL to 10 mg / mL, 2 mg / mL to

[0112] 9 mg / mL, 2 mg / mL to 8 mg / mL, 2 mg / mL to 7 mg / mL, 2 mg / mL to 6 mg / mL, 2 mg / mL to 5 mg / mL, 2 mg / mL to 4 mg / mL, 2 mg / mL to 3 mg / mL, 2 mg / mL to 25 mg / mL, 2.5 mg / mL to 10 mg / mL, 2.5 mg / mL to 9 mg / mL, 2.5 mg / mL to 8 mg / mL, 2.5 mg / mL to 7 mg / mL, 2.5 mg / mL to 6 mg / mL, 2.5 mg / mL to 5 mg / mL, 2.5 mg / mL to 4 mg / mL, 2.5 mg / mL to 3 mg / mL, 3 mg / mL to

[0113] 10 mg / mL, 3 mg / mL to 9 mg / mL, 3 mg / mL to 8 mg / mL, 3 mg / mL to 7 mg / mL, 3 mg / mL to 6 mg / mL, 3 mg / mL to 5 mg / mL, 3 mg / mL to 4 mg / mL, 4 mg / mL to 10 mg / mL, 4 mg / mL to 9 mg / mL, 4 mg / mL to 8 mg / mL, 4 mg / mL to 7 mg / mL, 4 mg / mL to 6 mg / mL, 4 mg / mL to 5 mg / mL, 5 mg / mL to 10 mg / mL, 5 mg / mL to 9 mg / mL, 5 mg / mL to 8 mg / mL, 5 mg / mL to 7 mg / mL, 5 mg / mL to 6 mg / mL, 6 mg / mL to 10 mg / mL, 6 mg / mL to 9 mg / mL, 6 mg / mL to 8 mg / mL, 6 mg / mL to 7 mg / mL, 7 mg / mL to 10 mg / mL, 7 mg / mL to 9 mg / mL, 7 mg / mL to 8 mg / mL, 8 mg / mL to 10 mg / mL, 8 mg / mL to 9 mg / mL, or 9 mg / mL to 10 mg / mL) of EDTA or a salt thereof (e.g., tetrasodium EDTA or disodium EDTA).

[0114] In certain preferred embodiments, the liquid carrier comprises 0.1 mg / mL to 5 mg / mL (e.g., 0.1 mg / mL to 4 mg / mL, 0.1 mg / mL to 3 mg / mL, 0.1 mg / mL to 2.5 mg / mL, 0.1 mg / mL to 2 mg / mL, 0.1 mg / mL to 1.5 mg / mL, 0.1 mg / mL to 1 mg / mL, 0.1 mg / mL to 0.7 mg / mL, 0.1 mg / mL to 0.5 mg / mL, 0.2 mg / mL to 5 mg / mL, 0.2 mg / mL to 4 mg / mL, 0.2 mg / mL to 3 mg / mL, 0.2 mg / mL to 2.5 mg / mL, 0.2 mg / mL to 2 mg / mL, 0.2 mg / mL to 1.5 mg / mL, 0.2 mg / mL to 1 mg / mL, 0.2 mg / mL to 0.7 mg / mL, 0.2 mg / mL to 0.5 mg / mL, 0.3 mg / mL to 5 mg / mL, 0.3 mg / mL to 4 mg / mL, 0.3 mg / mL to 3 mg / mL, 0.3 mg / mL to 2.5 mg / mL, 0.3 mg / mL to 2 mg / mL, 0.3 mg / mL to 1.5 mg / mL, 0.3 mg / mL to 1 mg / mL, 0.3 mg / mL to 0.7 mg / mL, 0.3 mg / mL to 0.5 mg / mL, 0.4 mg / mL to 5 mg / mL, 0.4 mg / mL to 4 mg / mL, 0.4 mg / mL to 3 mg / mL, 0.4 mg / mL to

[0115] 2.5 mg / mL, 0.4 mg / mL to 2 mg / mL, 0.4 mg / mL to 1.5 mg / mL, 0.4 mg / mL to 1 mg / mL, 0.4 mg / mL to 0.7 mg / mL, 0.4 mg / mL to 0.5 mg / mL, 0.5 mg / mL to 5 mg / mL, 0.5 mg / mL to 4 mg / mL, 0.5 mg / mL to 3 mg / mL, 0.5 mg / mL to 2.5 mg / mL, 0.5 mg / mL to 2 mg / mL, 0.5 mg / mL to 1.5 mg / mL, 0.5 mg / mL to 1 mg / mL, 0.5 mg / mL to 0.7 mg / mL, 1 mg / mL to 5 mg / mL, 1 mg / mL to 4 mg / mL, 1 mg / mL to 3 mg / mL, 1 mg / mL to 2.5 mg / mL, 1 mg / mL to 2 mg / mL, 1 mg / mL to 1.5 mg / mL, 1.5 mg / mL to 5 mg / mL, 1.5 mg / mL to 4 mg / mL, 1.5 mg / mL to 3 mg / mL,

[0116] 1.5 mg / mL to 2.5 mg / mL, 1.5 mg / mL to 2 mg / mL, 2 mg / mL to 5 mg / mL, 2 mg / mL to 4 mg / mL, 2 mg / mL to 3 mg / mL, 2 mg / mL to 2.5 mg / mL, 2.5 mg / mL to 5 mg / mL, 2.5 mg / mL to 4 mg / mL,

[0117] 2.5 mg / mL to 3 mg / mL, 3 mg / mL to 5 mg / mL, 3 mg / mL to 4 mg / mL, or 4 mg / mL to 5 mg / mL) of EDTA or a salt thereof (e.g., tetrasodium EDTA or disodium EDTA). In some particularly preferred embodiments, the liquid carrier comprises 0.5 mg / mL to 5 mg / mL of EDTA or a salt thereof (e.g., tetrasodium EDTA or disodium EDTA).

[0118] In certain preferred embodiments (e.g., for compositions including two or more therapeutic agents described herein), the liquid carrier includes 0.1 mg / mL to 3 mg / mL (e.g., 0.1 mg / mL to 2.5 mg / mL, 0.1 mg / mL to 2 mg / mL, 0.1 mg / mL to 1.5 mg / mL, 0.1 mg / mL to 1 mg / mL , 0.1 mg / mL to 0.7 mg / mL, 0.1 mg / mL to 0.5 mg / mL, 0.2 mg / mL to 3 mg / mL, 0.2 mg / mL to 2.5 mg / mL, 0.2 mg / mL to 2 mg / mL, 0.2 mg / mL to 1.5 mg / mL, 0.2 mg / mL to 1 mg / mL, 0.2 mg / mL to 0.5 mg / mL, 0.3 mg / mL to 3 mg / mL, 0.3 mg / mL to 2.5 mg / mL, 0.3 mg / mL to 2 mg / mL, 0.3 mg / mL to 1.5 mg / mL, 0.3 mg / mL to 1 mg / mL, 0.3 mg / mL to 0.7 mg / mL, 0.3 mg / mL to 0.5 mg / mL, 0.4 mg / mL to 3 mg / mL, 0.4 mg / mL to 2.5 mg / mL, 0.4 mg / mL to 2 mg / mL, 0.4 mg / mL to 1.5 mg / mL, 0.4 mg / mL to 1 mg / mL, 0.4 mg / mL to 0.7 mg / mL, 0.4 mg / mL to 0.5 mg / mL, 0.5 mg / mL to 3 mg / mL, 0.5 mg / mL to 2.5 mg / mL, 0.5 mg / mL to 2 mg / mL, 0.5 mg / mL to 1.5 mg / mL, 0.5 mg / mL to 1 mg / mL, 1 mg / mL to 3 mg / mL, 1 mg / mL to 2.5 mg / mL, 1 mg / mL to 2 mg / mL, 1 mg / mL to 1.5 mg / mL, 1.5 mg / mL to 3 mg / mL,

[0119] 1.5 mg / mL to 2.5 mg / mL, 1.5 mg / mL to 2 mg / mL, 2 mg / mL to 3 mg / mL, 2 mg / mL to 2.5 mg / mL, or 2.5 mg / mL to 3 mg / mL) of EDTA or a salt thereof (e.g., tetrasodium EDTA or disodium EDTA).

[0120] In further preferred embodiments (e.g., for compositions described herein including atorvastatin or salt thereof (e.g., atorvastatin calcium) as the only therapeutic agent), the liquid carrier includes 0.5 mg / mL to 5 mg / mL (e.g., 0.5 mg / mL to 4 mg / mL, 0.5 mg / mL to 3 mg / mL, 0.5 mg / mL to 2.5 mg / mL, 0.5 mg / mL to 2 mg / mL, 0.5 mg / mL to 1.5 mg / mL, 0.5 mg / ml to 1.0 mg / ml, 0.5 mg / ml to 0.7 mg / ml, 1.0 mg / mL to 4 mg / mL, 1.0 mg / mL to 3 mg / mL, 1.0 mg / mL to

[0121] 2.5 mg / mL, 1.0 mg / mL to 2 mg / mL, 1.0 mg / mL to 1.5 mg / mL, 1.5 mg / mL to 5 mg / mL, 1.5 mg / mL to 4 mg / mL, 1.5 mg / mL to 3 mg / mL, 1.5 mg / mL to 2.5 mg / mL, 1.5 mg / mL to 2 mg / mL, 2 mg / mL to 5 mg / mL, 2 mg / mL to 4 mg / mL, 2 mg / mL to 3 mg / mL, 2 mg / mL to 2.5 mg / mL, 2.5 mg / mL to 5 mg / mL, 2.5 mg / mL to 4 mg / mL, 2.5 mg / mL to 3 mg / mL, 3 mg / mL to 5 mg / mL, 3 mg / mL to 4 mg / mL, or 4 mg / mL to 5 mg / mL) EDTA or a salt thereof (e.g., tetrasodium EDTA or disodium EDTA). Meglumine

[0122] In certain embodiments, the liquid carrier comprises meglumine or a salt thereof. In some embodiments, the liquid carrier comprises 0.01% to 1.0% (w / w) meglumine or a salt thereof. In certain embodiments, the liquid carrier comprises 0.05% to 0.8% (w / w), 0.1% to 0.7% (w / w), 0.1% to 0.5% (w / w), or about 0.3% (w / w) meglumine or a salt thereof.

[0123] In certain embodiments, the liquid carrier comprises 1 mg / mL to 550 mg / mL (e.g., 1 mg / mL to 500 mg / mL, 1 mg / mL to 400 mg / mL, 1 mg / ml to 300 mg / mL, 1 mg / ml to 250 mg / mL, 1 mg / mL to 200 mg / mL, 1 mg / mL to 150 mg / mL, 1 mg / mL to 100 mg / mL, 1 mg / mL to 75 mg / ml, 1 mg / mL to 60 mg / mL, 1 mg / mL to 50 mg / mL, 1 mg / mL to 30 mg / mL, 1 mg / mL to 25 mg / mL, 1 mg / mL to 10 mg / mL, 5 mg / mL to 550 mg / mL, 5 mg / mL to 500 mg / mL, 5 mg / mL to 400 mg / mL, 5 mg / mL to 300 mg / mL, 5 mg / mL to 250 mg / mL, 5 mg / mL to 200 mg / mL, 5 mg / mL to 150 mg / mL, 5 mg / mL to 100 mg / mL, 5 mg / mL to 75 mg / mL, 5 mg / mL to 60 mg / mL, 5 mg / mL to 50 mg / mL, 5 mg / mL to 30 mg / mL, 5 mg / mL to 25 mg / mL, 5 mg / mL to 10 mg / mL, 10 mg / mL to 550 mg / mL, 10 mg / mL to 500 mg / mL, 10 mg / mL to 400 mg / mL, 10 mg / mL to 300 mg / mL, 10 mg / mL to 250 mg / mL, 10 mg / mL to 200 mg / mL, 10 mg / mL to 150 mg / mL, 10 mg / mL to 100 mg / mL, 10 mg / mL to 75 mg / mL, 10 mg / mL to 60 mg / mL, 10 mg / mL to 50 mg / mL, 10 mg / mL to 30 mg / mL, 10 mg / mL to 25 mg / mL, 25 mg / mL to 550 mg / mL, 25 mg / mL to 500 mg / mL, 25 mg / mL to 400 mg / mL, 25 mg / mL to 300 mg / mL, 25 mg / mL to 250 mg / mL, 25 mg / mL to 200 mg / mL, 25 mg / mL to 150 mg / mL, 25 mg / mL to 100 mg / mL, 25 mg / mL to 75 mg / mL, 25 mg / mL to 60 mg / mL, 25 mg / mL to 50 mg / mL, 25 mg / mL to 30 mg / mL, 50 mg / mL to 550 mg / mL, 50 mg / mL to 500 mg / mL, 50 mg / mL to 400 mg / mL, 50 mg / mL to 300 mg / mL, 50 mg / mL to 250 mg / mL, 50 mg / mL to 200 mg / mL, 50 mg / mL to 150 mg / mL, 50 mg / mL to 100 mg / mL, 50 mg / mL to 75 mg / mL, 50 mg / mL to 60 mg / mL, 60 mg / mL to 550 mg / mL, 60 mg / mL to 500 mg / mL, 60 mg / mL to 400 mg / mL, 60 mg / mL to 300 mg / mL, 60 mg / mL to 250 mg / mL, 60 mg / mL to 200 mg / mL, 60 mg / mL to 150 mg / mL, 60 mg / mL to 100 mg / mL, 60 mg / mL to 75 mg / mL, 75 mg / mL to 550 mg / mL, 75 mg / mL to 500 mg / mL, 75 mg / mL to 400 mg / mL, 75 mg / mL to 300 mg / mL, 75 mg / mL to 250 mg / mL, 75 mg / mL to 200 mg / mL, 75 mg / mL to 150 mg / mL, 75 mg / mL to 100 mg / mL, 100 mg / mL to 550 mg / mL, 100 mg / mL to 500 mg / mL, 100 mg / mL to 400 mg / mL, 100 mg / mL to 300 mg / mL, 100 mg / mL to 250 mg / mL, 100 mg / mL to 200 mg / mL, 100 mg / mL to 150 mg / mL, 150 mg / mL to 550 mg / mL, 150 mg / mL to 500 mg / mL, 150 mg / mL to 400 mg / mL, 150 mg / mL to 300 mg / mL, 150 mg / mL to 250 mg / mL, 150 mg / mL to 200 mg / mL, 200 mg / mL to 550 mg / mL, 200 mg / mL to 500 mg / mL, 200 mg / mL to 400 mg / mL, 200 mg / mL to 300 mg / mL, 200 mg / mL to 250 mg / mL, 250 mg / mL to 550 mg / mL, 250 mg / mL to 500 mg / mL, 250 mg / mL to 400 mg / mL, 250 mg / mL to 300 mg / mL, 300 mg / mL to 550 mg / mL, 300 mg / mL to 500 mg / mL, 300 mg / mL to 400 mg / mL, 400 mg / mL to 550 mg / mL, or 400 mg / mL to 500 mg / mL) of meglumine or a salt thereof.

[0124] In certain embodiments, the liquid carrier comprises 1 mg / mL to 100 mg / mL (e.g., 1 mg / mL to 90 mg / mL, 1 mg / mL to 80 mg / mL, 1 mg / mL to 70 mg / mL, 1 mg / mL to 60 mg / mL, 1 mg / mL to 50 mg / mL, 1 mg / mL to 40 mg / mL, 1 mg / mL to 30 mg / mL, 1 mg / mL to 25 mg / mL, 1 mg / mL to 20 mg / mL, 1 mg / mL to 15 mg / mL, 1 mg / mL to 10 mg / mL, 1 mg / mL to 5 mg / mL, 2 mg / mL to 100 mg / mL, 2 mg / mL to 90 mg / mL, 2 mg / mL to 80 mg / mL, 2 mg / mL to 70 mg / mL, 2 mg / mL to 60 mg / mL, 2 mg / mL to 50 mg / mL, 2 mg / mL to 40 mg / mL, 2 mg / mL to 30 mg / mL, 2 mg / mL to 25 mg / mL, 2 mg / mL to 20 mg / mL, 2 mg / mL to 15 mg / mL, 2 mg / mL to 10 mg / mL, 2 mg / mL to 5 mg / mL, 3 mg / mL to 100 mg / mL, 3 mg / mL to 90 mg / mL, 3 mg / mL to 80 mg / mL, 3 mg / mL to 70 mg / mL, 3 mg / mL to 60 mg / mL, 3 mg / mL to 50 mg / mL, 3 mg / mL to 40 mg / mL, 3 mg / mL to 30 mg / mL, 3 mg / mL to 25 mg / mL, 3 mg / mL to 20 mg / mL, 3 mg / mL to 15 mg / mL, 3 mg / mL to 10 mg / mL, 3 mg / mL to 5 mg / mL, 4 mg / mL to 100 mg / mL, 4 mg / mL to 90 mg / mL, 4 mg / mL to 80 mg / mL, 4 mg / mL to 70 mg / mL, 4 mg / mL to 60 mg / mL, 4 mg / mL to 50 mg / mL, 4 mg / mL to 40 mg / mL, 4 mg / mL to 30 mg / mL, 4 mg / mL to 25 mg / mL, 4 mg / mL to 20 mg / mL, 4 mg / mL to 15 mg / mL, 4 mg / mL to 10 mg / mL, 4 mg / mL to 5 mg / mL, 5 mg / mL to 100 mg / mL, 5 mg / mL to 90 mg / mL, 5 mg / mL to 80 mg / mL, 5 mg / mL to 70 mg / mL, 5 mg / mL to 60 mg / mL, 5 mg / mL to 50 mg / mL, 5 mg / mL to 40 mg / mL, 5 mg / mL to 30 mg / mL, 5 mg / mL to 25 mg / mL, 5 mg / mL to 20 mg / mL, 5 mg / mL to 15 mg / mL, 5 mg / mL to 10 mg / mL, 10 mg / mL to 100 mg / mL, 10 mg / mL to 90 mg / mL, 10 mg / mL to 80 mg / mL, 10 mg / mL to 70 mg / mL, 10 mg / mL to 60 mg / mL, 10 mg / mL to 50 mg / mL, 10 mg / mL to 40 mg / mL, 10 mg / mL to 30 mg / mL, 10 mg / mL to 25 mg / mL, 10 mg / mL to 20 mg / mL, 10 mg / mL to 15 mg / mL, 15 mg / mL to 100 mg / mL, 15 mg / mL to 90 mg / mL, 15 mg / mL to 80 mg / mL, 15 mg / mL to 70 mg / mL, 15 mg / mL to 60 mg / mL, 15 mg / mL to 50 mg / mL, 15 mg / mL to 40 mg / mL, 15 mg / mL to 30 mg / mL, 15 mg / mL to 25 mg / mL, 15 mg / mL to 20 mg / mL, 20 mg / mL to 100 mg / mL, 20 mg / mL to 90 mg / mL, 20 mg / mL to 80 mg / mL, 20 mg / mL to 70 mg / mL, 20 mg / mL to 60 mg / mL, 20 mg / mL to 50 mg / mL, 20 mg / mL to 40 mg / mL, 20 mg / mL to 30 mg / mL, 20 mg / mL to 25 mg / mL, 25 mg / mL to 100 mg / mL, 25 mg / mL to 90 mg / mL, 25 mg / mL to 80 mg / mL, 25 mg / mL to 70 mg / mL, 25 mg / mL to 60 mg / mL, 25 mg / mL to 50 mg / mL, 25 mg / mL to 40 mg / mL, 25 mg / mL to 30 mg / mL, 30 mg / mL to 100 mg / mL, 30 mg / mL to 90 mg / mL, 30 mg / mL to 80 mg / mL, 30 mg / mL to 70 mg / mL, 30 mg / mL to 60 mg / mL, 30 mg / mL to 50 mg / mL, 30 mg / mL to 40 mg / mL, 40 mg / mL to 100 mg / mL, 40 mg / mL to 90 mg / mL, 40 mg / mL to 80 mg / mL, 40 mg / mL to 70 mg / mL, 40 mg / mL to 60 mg / mL, 40 mg / mL to 50 mg / mL, 50 mg / mL to 100 mg / mL, 50 mg / mL to 90 mg / mL, 50 mg / mL to 80 mg / mL, 50 mg / mL to 70 mg / mL, 50 mg / mL to 60 mg / mL, 60 mg / mL to 100 mg / mL, 60 mg / mL to 90 mg / mL, 60 mg / mL to 80 mg / mL, 60 mg / mL to 70 mg / mL, 70 mg / mL to 100 mg / mL, 70 mg / mL to 90 mg / mL, 70 mg / mL to 80 mg / mL, 80 mg / mL to 100 mg / mL, 80 mg / mL to 90 mg / mL, or 90 mg / mL to 100 mg / mL) of meglumine or a salt thereof.

[0125] In certain preferred embodiments, the liquid carrier comprises 1 mg / mL to 50 mg / mL (e.g., 1 mg / mL to 40 mg / mL, 1 mg / mL to 30 mg / mL, 1 mg / mL to 25 mg / mL, 1 mg / mL to 20 mg / mL, 1 mg / mL to 15 mg / mL, 1 mg / mL to 10 mg / mL, 1 mg / mL to 5 mg / mL, 2 mg / mL to 50 mg / mL, 2 mg / mL to 40 mg / mL, 2 mg / mL to 30 mg / mL, 2 mg / mL to 25 mg / mL, 2 mg / mL to 20 mg / mL, 2 mg / mL to 15 mg / mL, 2 mg / mL to 10 mg / mL, 2 mg / mL to 5 mg / mL, 3 mg / mL to 50 mg / mL, 3 mg / mL to 40 mg / mL, 3 mg / mL to 30 mg / mL, 3 mg / mL to 25 mg / mL, 3 mg / mL to 20 mg / mL, 3 mg / mL to 15 mg / mL, 3 mg / mL to 10 mg / mL, 3 mg / mL to 5 mg / mL, 4 mg / mL to 50 mg / mL, 4 mg / mL to 40 mg / mL, 4 mg / mL to 30 mg / mL, 4 mg / mL to 25 mg / mL, 4 mg / mL to 20 mg / mL, 4 mg / mL to 15 mg / mL, 4 mg / mL to 10 mg / mL, 4 mg / mL to 5 mg / mL, 5 mg / mL to 50 mg / mL, 5 mg / mL to 40 mg / mL, 5 mg / mL to 30 mg / mL, 5 mg / mL to 25 mg / mL, 5 mg / mL to 20 mg / mL, 5 mg / mL to 15 mg / mL, 5 mg / mL to 10 mg / mL, 10 mg / mL to 50 mg / mL, 10 mg / mL to 40 mg / mL, 10 mg / mL to 30 mg / mL, 10 mg / mL to 25 mg / mL, 10 mg / mL to 20 mg / mL, 10 mg / mL to 15 mg / mL, 15 mg / mL to 50 mg / mL, 15 mg / mL to 40 mg / mL, 15 mg / mL to 30 mg / mL, 15 mg / mL to 25 mg / mL, 15 mg / mL to 20 mg / mL, 20 mg / mL to 50 mg / mL, 20 mg / mL to 40 mg / mL, 20 mg / mL to 30 mg / mL, 20 mg / mL to 25 mg / mL, 25 mg / mL to 50 mg / mL, 25 mg / mL to 40 mg / mL, 25 mg / mL to 30 mg / mL, 30 mg / mL to 50 mg / mL, 30 mg / mL to 40 mg / mL, or 40 mg / mL to 50 mg / mL) of meglumine or a salt thereof. In more preferred embodiments, the liquid carrier includes 5 mg / mL to 50 mg / mL of meglumine or a salt thereof.

[0126] In certain preferred embodiments (e.g., for liquid pharmaceutical compositions described herein including atorvastatin or a salt thereof (e.g., atorvastatin calcium) as the only therapeutic

[0127] -Zi agent), the composition includes 1 mg / mL to 30 mg / mL (e.g., 1 mg / mL to 25 mg / mL, 1 mg / mL to 20 mg / mL, 1 mg / mL to 15 mg / mL, 1 mg / mL to 10 mg / mL, 1 mg / mL to 5 mg / mL, 2 mg / mL to 30 mg / mL, 2 mg / mL to 25 mg / mL, 2 mg / mL to 20 mg / mL, 2 mg / mL to 15 mg / mL, 2 mg / mL to 10 mg / mL, 2 mg / mL to 5 mg / mL, 3 mg / mL to 30 mg / mL, 3 mg / mL to 25 mg / mL, 3 mg / mL to 20 mg / mL, 3 mg / mL to 15 mg / mL, 3 mg / mL to 10 mg / mL, 3 mg / mL to 5 mg / mL, 4 mg / mL to 30 mg / mL, 4 mg / mL to 25 mg / mL, 4 mg / mL to 20 mg / mL, 4 mg / mL to 15 mg / mL, 4 mg / mL to 10 mg / mL, 4 mg / mL to 5 mg / mL, 5 mg / mL to 30 mg / mL, 5 mg / mL to 25 mg / mL, 5 mg / mL to 20 mg / mL, 5 mg / mL to 15 mg / mL, 5 mg / mL to 10 mg / mL, 10 mg / mL to 30 mg / mL, 10 mg / mL to 25 mg / mL, 10 mg / mL to 20 mg / mL, 10 mg / mL to 15 mg / mL, 15 mg / mL to 30 mg / mL, 15 mg / mL to 25 mg / mL, 15 mg / mL to 20 mg / mL, 20 mg / mL to 30 mg / mL, 20 mg / mL to 25 mg / mL, or 25 mg / mL to 30 mg / mL) of meglumine.

[0128] Propylene glycol

[0129] In certain embodiments, the liquid carrier comprises propylene glycol. In some embodiments, the liquid carrier comprises 0.1% to 10% (w / w) propylene glycol. In certain embodiments, the liquid carrier comprises 0.2% to 8% (w / w), 0.5% to 5% (w / w), 1% to 5% (w / w), or about 3% (w / w) propylene glycol.

[0130] In certain embodiments, the liquid carrier comprises 1 mg / mL to 500 mg / mL (e.g., 1 mg / mL to 450 mg / mL, 1 mg / mL to 400 mg / mL, 1 mg / ml to 300 mg / mL, 1 mg / ml to 250 mg / mL, 1 mg / mL to 200 mg / mL, 1 mg / mL to 150 mg / mL, 1 mg / mL to 100 mg / mL, 1 mg / mL to 75 mg / ml, 1 mg / mL to 60 mg / mL, 1 mg / mL to 50 mg / mL, 1 mg / mL to 30 mg / mL, 1 mg / mL to 25 mg / mL, 1 mg / mL to 10 mg / mL, 5 mg / mL to 500 mg / mL, 5 mg / mL to 400 mg / mL, 5 mg / mL to 300 mg / mL, 5 mg / mL to 250 mg / mL, 5 mg / mL to 200 mg / mL, 5 mg / mL to 150 mg / mL, 5 mg / mL to 100 mg / mL, 5 mg / mL to 75 mg / mL, 5 mg / mL to 60 mg / mL, 5 mg / mL to 50 mg / mL, 5 mg / mL to 30 mg / mL, 5 mg / mL to 25 mg / mL, 5 mg / mL to 10 mg / mL, 10 mg / mL to 500 mg / mL, 10 mg / mL to 400 mg / mL, 10 mg / mL to 300 mg / mL, 10 mg / mL to 250 mg / mL, 10 mg / mL to 200 mg / mL, 10 mg / mL to 150 mg / mL, 10 mg / mL to 100 mg / mL, 10 mg / mL to 75 mg / mL, 10 mg / mL to 60 mg / mL, 10 mg / mL to 50 mg / mL, 10 mg / mL to 30 mg / mL, 10 mg / mL to 25 mg / mL, 25 mg / mL to 500 mg / mL, 25 mg / mL to 400 mg / mL, 25 mg / mL to 300 mg / mL, 25 mg / mL to 250 mg / mL, 25 mg / mL to 200 mg / mL, 25 mg / mL to 150 mg / mL, 25 mg / mL to 100 mg / mL, 25 mg / mL to 75 mg / mL, 25 mg / mL to 60 mg / mL, 25 mg / mL to 50 mg / mL, 25 mg / mL to 30 mg / mL, 50 mg / mL to 500 mg / mL, 50 mg / mL to 400 mg / mL, 50 mg / mL to 300 mg / mL, 50 mg / mL to 250 mg / mL, 50 mg / mL to 200 mg / mL, 50 mg / mL to 150 mg / mL, 50 mg / mL to 100 mg / mL, 50 mg / mL to 75 mg / mL, 50 mg / mL to 60 mg / mL, 60 mg / mL to 500 mg / mL, 60 mg / mL to 400 mg / mL, 60 mg / mL to 300 mg / mL, 60 mg / mL to 250 mg / mL, 60 mg / mL to 200 mg / mL, 60 mg / mL to 150 mg / mL, 60 mg / mL to 100 mg / mL, 60 mg / mL to 75 mg / mL, 75 mg / mL to 500 mg / mL, 75 mg / mL to 400 mg / mL, 75 mg / mL to 300 mg / mL, 75 mg / mL to 250 mg / mL, 75 mg / mL to 200 mg / mL, 75 mg / mL to 150 mg / mL, 75 mg / mL to 100 mg / mL, 100 mg / mL to 500 mg / mL, 100 mg / mL to 400 mg / mL, 100 mg / mL to 300 mg / mL, 100 mg / mL to 250 mg / mL, 100 mg / mL to 200 mg / mL, 100 mg / mL to 150 mg / mL, 150 mg / mL to 500 mg / mL, 150 mg / mL to 400 mg / mL, 150 mg / mL to 300 mg / mL, 150 mg / mL to 250 mg / mL, 150 mg / mL to 200 mg / mL, 200 mg / mL to 500 mg / mL, 200 mg / mL to 400 mg / mL, 200 mg / mL to 300 mg / mL, 200 mg / mL to 250 mg / mL, 250 mg / mL to 500 mg / mL, 250 mg / mL to 400 mg / mL, 250 mg / mL to 300 mg / mL, 300 mg / mL to 500 mg / mL, 300 mg / mL to 400 mg / mL, or 400 mg / mL to 500 mg / mL) of propylene glycol.

[0131] In certain embodiments, the liquid carrier comprises 10 mg / mL to 250 mg / mL (e.g., 10 mg / mL to 220 mg / mL, 10 mg / mL to 200 mg / mL, 10 mg / mL to 180 mg / mL, 10 mg / mL to 170 mg / mL, 10 mg / mL to 160 mg / mL, 10 mg / mL to 150 mg / mL, 10 mg / mL to 140 mg / mL, 10 mg / mL to 130 mg / mL, 10 mg / mL to 120 mg / mL, 10 mg / mL to 110 mg / mL, 10 mg / mL to 100 mg / mL, 10 mg / mL to 90 mg / mL, 10 mg / mL to 80 mg / mL, 10 mg / mL to 70 mg / mL, 10 mg / mL to 60 mg / mL, 10 mg / ml to 50 mg / ml, 10 mg / ml to 40 mg / ml, 10 mg / ml to 30 mg / ml, 10 mg / ml to 20 mg / ml, 20 mg / mL to 220 mg / mL, 20 mg / mL to 200 mg / mL, 20 mg / mL to 180 mg / mL, 20 mg / mL to 170 mg / mL, 20 mg / mL to 160 mg / mL, 20 mg / mL to 150 mg / mL, 20 mg / mL to 140 mg / mL, 20 mg / mL to 130 mg / mL, 20 mg / mL to 120 mg / mL, 20 mg / mL to 110 mg / mL, 20 mg / mL to 100 mg / mL, 20 mg / mL to 90 mg / mL, 20 mg / mL to 80 mg / mL, 20 mg / mL to 70 mg / mL, 20 mg / mL to 60 mg / mL, 20 mg / ml to 50 mg / ml, 20 mg / ml to 40 mg / ml, 20 mg / ml to 30 mg / ml, 30 mg / mL to 220 mg / mL, 30 mg / mL to 200 mg / mL, 30 mg / mL to 180 mg / mL, 30 mg / mL to 170 mg / mL, 30 mg / mL to 160 mg / mL, 30 mg / mL to 150 mg / mL, 30 mg / mL to 140 mg / mL, 30 mg / mL to 130 mg / mL, 30 mg / mL to 120 mg / mL, 30 mg / mL to 110 mg / mL, 30 mg / mL to 100 mg / mL, 30 mg / mL to 90 mg / mL, 30 mg / mL to 80 mg / mL, 30 mg / mL to 70 mg / mL, 30 mg / mL to 60 mg / mL, 30 mg / ml to 50 mg / ml, 30 mg / ml to 40 mg / ml, 50 mg / mL to 220 mg / mL, 50 mg / mL to 200 mg / mL, 50 mg / mL to 180 mg / mL, 50 mg / mL to 170 mg / mL, 50 mg / mL to 160 mg / mL, 50 mg / mL to 150 mg / mL, 50 mg / mL to 140 mg / mL, 50 mg / mL to 130 mg / mL, 50 mg / mL to 120 mg / mL, 50 mg / mL to 110 mg / mL, 50 mg / mL to 100 mg / mL, 50 mg / mL to 90 mg / mL, 50 mg / mL to 80 mg / mL, 50 mg / mL to 70 mg / mL, 50 mg / mL to 60 mg / mL, 75 mg / mL to 220 mg / mL, 75 mg / mL to 200 mg / mL, 75 mg / mL to 180 mg / mL, 75 mg / mL to 170 mg / mL, 75 mg / mL to 160 mg / mL, 75 mg / mL to 150 mg / mL, 75 mg / mL to 140 mg / mL, 75 mg / mL to 130 mg / mL, 75 mg / mL to 120 mg / mL, 75 mg / mL to 110 mg / mL, 75 mg / mL to 100 mg / mL, 75 mg / mL to 90 mg / mL, 75 mg / mL to 80 mg / mL, 100 mg / mL to 220 mg / mL, 100 mg / mL to 200 mg / mL, 100 mg / mL to 180 mg / mL, 100 mg / mL to 170 mg / mL, 100 mg / mL to 160 mg / mL, 100 mg / mL to 150 mg / mL, 100 mg / mL to 140 mg / mL, 100 mg / mL to 130 mg / mL, 100 mg / mL to 120 mg / mL, 100 mg / mL to 110 mg / mL, 100 mg / mL to 100 mg / mL, 100 mg / mL to 90 mg / mL, 150 mg / mL to 220 mg / mL, 150 mg / mL to 200 mg / mL, 150 mg / mL to 180 mg / mL, 150 mg / mL to 170 mg / mL, 150 mg / mL to 160 mg / mL, 175 mg / mL to 220 mg / mL, 175 mg / mL to 200 mg / mL, or 200 mg / mL to 220 mg / mL) of propylene glycol.

[0132] Polyethylene glycol

[0133] In certain embodiments, the liquid carrier comprises polyethylene glycol. In certain embodiments, the liquid carrier comprises PEG400, PEG200, PEG 300, or EPG800. In some embodiments, the liquid carrier comprises PEG400. In certain embodiments, the liquid carrier comprises 1 mg / mL to 500 mg / mL (e.g., 1 mg / mL to 450 mg / mL, 1 mg / mL to 400 mg / mL, 1 mg / ml to 300 mg / mL, 1 mg / ml to 250 mg / mL, 1 mg / mL to 200 mg / mL, 1 mg / mL to 150 mg / mL, 1 mg / mL to 100 mg / mL, 1 mg / mL to 75 mg / ml, 1 mg / mL to 60 mg / mL, 1 mg / mL to 50 mg / mL, 1 mg / mL to 30 mg / mL, 1 mg / mL to 25 mg / mL, 1 mg / mL to 10 mg / mL, 5 mg / mL to 500 mg / mL, 5 mg / mL to 400 mg / mL, 5 mg / mL to 300 mg / mL, 5 mg / mL to 250 mg / mL, 5 mg / mL to 200 mg / mL, 5 mg / mL to 150 mg / mL, 5 mg / mL to 100 mg / mL, 5 mg / mL to 75 mg / mL, 5 mg / mL to 60 mg / mL, 5 mg / mL to 50 mg / mL, 5 mg / mL to 30 mg / mL, 5 mg / mL to 25 mg / mL, 5 mg / mL to 10 mg / mL, 10 mg / mL to 500 mg / mL, 10 mg / mL to 400 mg / mL, 10 mg / mL to 300 mg / mL, 10 mg / mL to 250 mg / mL, 10 mg / mL to 200 mg / mL, 10 mg / mL to 150 mg / mL, 10 mg / mL to 100 mg / mL, 10 mg / mL to 75 mg / mL, 10 mg / mL to 60 mg / mL, 10 mg / mL to 50 mg / mL, 10 mg / mL to 30 mg / mL, 10 mg / mL to 25 mg / mL, 25 mg / mL to 500 mg / mL, 25 mg / mL to 400 mg / mL, 25 mg / mL to 300 mg / mL, 25 mg / mL to 250 mg / mL, 25 mg / mL to 200 mg / mL, 25 mg / mL to 150 mg / mL, 25 mg / mL to 100 mg / mL, 25 mg / mL to 75 mg / mL, 25 mg / mL to 60 mg / mL, 25 mg / mL to 50 mg / mL, 25 mg / mL to 30 mg / mL, 50 mg / mL to 500 mg / mL, 50 mg / mL to 400 mg / mL, 50 mg / mL to 300 mg / mL, 50 mg / mL to 250 mg / mL, 50 mg / mL to 200 mg / mL, 50 mg / mL to 150 mg / mL, 50 mg / mL to 100 mg / mL, 50 mg / mL to 75 mg / mL, 50 mg / mL to 60 mg / mL, 60 mg / mL to 500 mg / mL, 60 mg / mL to 400 mg / mL, 60 mg / mL to 300 mg / mL, 60 mg / mL to 250 mg / mL, 60 mg / mL to 200 mg / mL, 60 mg / mL to 150 mg / mL, 60 mg / mL to 100 mg / mL, 60 mg / mL to 75 mg / mL, 75 mg / mL to 500 mg / mL, 75 mg / mL to 400 mg / mL, 75 mg / mL to 300 mg / mL, 75 mg / mL to 250 mg / mL, 75 mg / mL to 200 mg / mL, 75 mg / mL to 150 mg / mL, 75 mg / mL to 100 mg / mL, 100 mg / mL to 500 mg / mL, 100 mg / mL to 400 mg / mL, 100 mg / mL to 300 mg / mL, 100 mg / mL to 250 mg / mL, 100 mg / mL to 200 mg / mL, 100 mg / mL to 150 mg / mL, 150 mg / mL to 500 mg / mL, 150 mg / mL to 400 mg / mL, 150 mg / mL to 300 mg / mL, 150 mg / mL to 250 mg / mL, 150 mg / mL to 200 mg / mL, 200 mg / mL to 500 mg / mL, 200 mg / mL to 400 mg / mL, 200 mg / mL to 300 mg / mL, 200 mg / mL to 250 mg / mL, 250 mg / mL to 500 mg / mL, 250 mg / mL to 400 mg / mL, 250 mg / mL to 300 mg / mL, 300 mg / mL to 500 mg / mL, 300 mg / mL to 400 mg / mL, or 400 mg / mL to 500 mg / mL) of polyethylene glycol(e.g., PEG 400, PEG200, PEG300, or PEG800).

[0134] In certain embodiments, the liquid carrier comprises 10 mg / mL to 250 mg / mL (e.g., 10 mg / mL to 220 mg / mL, 10 mg / mL to 200 mg / mL, 10 mg / mL to 180 mg / mL, 10 mg / mL to 170 mg / mL, 10 mg / mL to 160 mg / mL, 10 mg / mL to 150 mg / mL, 10 mg / mL to 140 mg / mL, 10 mg / mL to 130 mg / mL, 10 mg / mL to 120 mg / mL, 10 mg / mL to 110 mg / mL, 10 mg / mL to 100 mg / mL, 10 mg / mL to 90 mg / mL, 10 mg / mL to 80 mg / mL, 10 mg / mL to 70 mg / mL, 10 mg / mL to 60 mg / mL, 10 mg / ml to 50 mg / ml, 10 mg / ml to 40 mg / ml, 10 mg / ml to 30 mg / ml, 10 mg / ml to 20 mg / ml, 20 mg / mL to 220 mg / mL, 20 mg / mL to 200 mg / mL, 20 mg / mL to 180 mg / mL, 20 mg / mL to 170 mg / mL, 20 mg / mL to 160 mg / mL, 20 mg / mL to 150 mg / mL, 20 mg / mL to 140 mg / mL, 20 mg / mL to 130 mg / mL, 20 mg / mL to 120 mg / mL, 20 mg / mL to 110 mg / mL, 20 mg / mL to 100 mg / mL, 20 mg / mL to 90 mg / mL, 20 mg / mL to 80 mg / mL, 20 mg / mL to 70 mg / mL, 20 mg / mL to 60 mg / mL, 20 mg / ml to 50 mg / ml, 20 mg / ml to 40 mg / ml, 20 mg / ml to 30 mg / ml, 30 mg / mL to 220 mg / mL, 30 mg / mL to 200 mg / mL, 30 mg / mL to 180 mg / mL, 30 mg / mL to 170 mg / mL, 30 mg / mL to 160 mg / mL, 30 mg / mL to 150 mg / mL, 30 mg / mL to 140 mg / mL, 30 mg / mL to 130 mg / mL, 30 mg / mL to 120 mg / mL, 30 mg / mL to 110 mg / mL, 30 mg / mL to 100 mg / mL, 30 mg / mL to 90 mg / mL, 30 mg / mL to 80 mg / mL, 30 mg / mL to 70 mg / mL, 30 mg / mL to 60 mg / mL, 30 mg / ml to 50 mg / ml, 30 mg / ml to 40 mg / ml, 50 mg / mL to 220 mg / mL, 50 mg / mL to 200 mg / mL, 50 mg / mL to 180 mg / mL, 50 mg / mL to 170 mg / mL, 50 mg / mL to 160 mg / mL, 50 mg / mL to 150 mg / mL, 50 mg / mL to 140 mg / mL, 50 mg / mL to 130 mg / mL, 50 mg / mL to 120 mg / mL, 50 mg / mL to 110 mg / mL, 50 mg / mL to 100 mg / mL, 50 mg / mL to 90 mg / mL, 50 mg / mL to 80 mg / mL, 50 mg / mL to 70 mg / mL, 50 mg / mL to 60 mg / mL, 75 mg / mL to 220 mg / mL, 75 mg / mL to 200 mg / mL, 75 mg / mL to 180 mg / mL, 75 mg / mL to 170 mg / mL, 75 mg / mL to 160 mg / mL, 75 mg / mL to 150 mg / mL, 75 mg / mL to 140 mg / mL, 75 mg / mL to 130 mg / mL, 75 mg / mL to 120 mg / mL, 75 mg / mL to 110 mg / mL, 75 mg / mL to 100 mg / mL, 75 mg / mL to 90 mg / mL, 75 mg / mL to 80 mg / mL, 100 mg / mL to 220 mg / mL, 100 mg / mL to 200 mg / mL, 100 mg / mL to 180 mg / mL, 100 mg / mL to 170 mg / mL, 100 mg / mL to 160 mg / mL, 100 mg / mL to 150 mg / mL, 100 mg / mL to 140 mg / mL, 100 mg / mL to 130 mg / mL, 100 mg / mL to 120 mg / mL, 100 mg / mL to 110 mg / mL, 100 mg / mL to 100 mg / mL, 100 mg / mL to 90 mg / mL, 150 mg / mL to 220 mg / mL, 150 mg / mL to 200 mg / mL, 150 mg / mL to 180 mg / mL, 150 mg / mL to 170 mg / mL, 150 mg / mL to 160 mg / mL, 175 mg / mL to 220 mg / mL, 175 mg / mL to 200 mg / mL, or 200 mg / mL to 220 mg / mL) of polyethylene glycol (e.g., PEG 400, PEG200, PEG300 or PEG800).

[0135] In certain embodiments, the liquid carrier comprises a combination of polyethylene glycol and propylene glycol at a ratio of 0.1 : 100 to 100:0.1 (weight by weight). In certain embodiments, the liquid carrier comprises 1 mg / mL to 500 mg / mL (e.g., 1 mg / mL to 450 mg / mL, 1 mg / mL to 400 mg / mL, 1 mg / ml to 300 mg / mL, 1 mg / ml to 250 mg / mL, 1 mg / mL to 200 mg / mL, 1 mg / mL to 150 mg / mL, 1 mg / mL to 100 mg / mL, 1 mg / mL to 75 mg / ml, 1 mg / mL to 60 mg / mL, 1 mg / mL to 50 mg / mL, 1 mg / mL to 30 mg / mL, 1 mg / mL to 25 mg / mL, 1 mg / mL to 10 mg / mL, 5 mg / mL to 500 mg / mL, 5 mg / mL to 400 mg / mL, 5 mg / mL to 300 mg / mL, 5 mg / mL to 250 mg / mL, 5 mg / mL to 200 mg / mL, 5 mg / mL to 150 mg / mL, 5 mg / mL to 100 mg / mL, 5 mg / mL to 75 mg / mL, 5 mg / mL to 60 mg / mL, 5 mg / mL to 50 mg / mL, 5 mg / mL to 30 mg / mL, 5 mg / mL to 25 mg / mL, 5 mg / mL to 10 mg / mL, 10 mg / mL to 500 mg / mL, 10 mg / mL to 400 mg / mL, 10 mg / mL to 300 mg / mL, 10 mg / mL to 250 mg / mL, 10 mg / mL to 200 mg / mL, 10 mg / mL to 150 mg / mL, 10 mg / mL to 100 mg / mL, 10 mg / mL to 75 mg / mL, 10 mg / mL to 60 mg / mL, 10 mg / mL to 50 mg / mL, 10 mg / mL to 30 mg / mL, 10 mg / mL to 25 mg / mL, 25 mg / mL to 500 mg / mL, 25 mg / mL to 400 mg / mL, 25 mg / mL to 300 mg / mL, 25 mg / mL to 250 mg / mL, 25 mg / mL to 200 mg / mL, 25 mg / mL to 150 mg / mL, 25 mg / mL to 100 mg / mL, 25 mg / mL to 75 mg / mL, 25 mg / mL to 60 mg / mL, 25 mg / mL to 50 mg / mL, 25 mg / mL to 30 mg / mL, 50 mg / mL to 500 mg / mL, 50 mg / mL to 400 mg / mL, 50 mg / mL to 300 mg / mL, 50 mg / mL to 250 mg / mL, 50 mg / mL to 200 mg / mL, 50 mg / mL to 150 mg / mL, 50 mg / mL to 100 mg / mL, 50 mg / mL to 75 mg / mL, 50 mg / mL to 60 mg / mL, 60 mg / mL to 500 mg / mL, 60 mg / mL to 400 mg / mL, 60 mg / mL to 300 mg / mL, 60 mg / mL to 250 mg / mL, 60 mg / mL to 200 mg / mL, 60 mg / mL to 150 mg / mL, 60 mg / mL to 100 mg / mL, 60 mg / mL to 75 mg / mL, 75 mg / mL to 500 mg / mL, 75 mg / mL to 400 mg / mL, 75 mg / mL to 300 mg / mL, 75 mg / mL to 250 mg / mL, 75 mg / mL to 200 mg / mL, 75 mg / mL to 150 mg / mL, 75 mg / mL to 100 mg / mL, 100 mg / mL to 500 mg / mL, 100 mg / mL to 400 mg / mL, 100 mg / mL to 300 mg / mL, 100 mg / mL to 250 mg / mL, 100 mg / mL to 200 mg / mL, 100 mg / mL to 150 mg / mL, 150 mg / mL to 500 mg / mL, 150 mg / mL to 400 mg / mL, 150 mg / mL to 300 mg / mL, 150 mg / mL to 250 mg / mL, 150 mg / mL to 200 mg / mL, 200 mg / mL to 500 mg / mL, 200 mg / mL to 400 mg / mL, 200 mg / mL to 300 mg / mL, 200 mg / mL to 250 mg / mL, 250 mg / mL to 500 mg / mL, 250 mg / mL to 400 mg / mL, 250 mg / mL to 300 mg / mL, 300 mg / mL to 500 mg / mL, 300 mg / mL to 400 mg / mL, or 400 mg / mL to 500 mg / mL) of the combination of polyethylene glycol with propylene glycol.

[0136] In certain embodiments, the liquid carrier comprises 10 mg / mL to 250 mg / mL (e.g., 10 mg / mL to 220 mg / mL, 10 mg / mL to 200 mg / mL, 10 mg / mL to 180 mg / mL, 10 mg / mL to 170 mg / mL, 10 mg / mL to 160 mg / mL, 10 mg / mL to 150 mg / mL, 10 mg / mL to 140 mg / mL, 10 mg / mL to 130 mg / mL, 10 mg / mL to 120 mg / mL, 10 mg / mL to 110 mg / mL, 10 mg / mL to 100 mg / mL, 10 mg / mL to 90 mg / mL, 10 mg / mL to 80 mg / mL, 10 mg / mL to 70 mg / mL, 10 mg / mL to 60 mg / mL, 10 mg / ml to 50 mg / ml, 10 mg / ml to 40 mg / ml, 10 mg / ml to 30 mg / ml, 10 mg / ml to 20 mg / ml, 20 mg / mL to 220 mg / mL, 20 mg / mL to 200 mg / mL, 20 mg / mL to 180 mg / mL, 20 mg / mL to 170 mg / mL, 20 mg / mL to 160 mg / mL, 20 mg / mL to 150 mg / mL, 20 mg / mL to 140 mg / mL, 20 mg / mL to 130 mg / mL, 20 mg / mL to 120 mg / mL, 20 mg / mL to 110 mg / mL, 20 mg / mL to 100 mg / mL, 20 mg / mL to 90 mg / mL, 20 mg / mL to 80 mg / mL, 20 mg / mL to 70 mg / mL, 20 mg / mL to 60 mg / mL, 20 mg / ml to 50 mg / ml, 20 mg / ml to 40 mg / ml, 20 mg / ml to 30 mg / ml, 30 mg / mL to 220 mg / mL, 30 mg / mL to 200 mg / mL, 30 mg / mL to 180 mg / mL, 30 mg / mL to 170 mg / mL, 30 mg / mL to 160 mg / mL, 30 mg / mL to 150 mg / mL, 30 mg / mL to 140 mg / mL, 30 mg / mL to 130 mg / mL, 30 mg / mL to 120 mg / mL, 30 mg / mL to 110 mg / mL, 30 mg / mL to 100 mg / mL, 30 mg / mL to 90 mg / mL, 30 mg / mL to 80 mg / mL, 30 mg / mL to 70 mg / mL, 30 mg / mL to 60 mg / mL, 30 mg / ml to 50 mg / ml, 30 mg / ml to 40 mg / ml, 50 mg / mL to 220 mg / mL, 50 mg / mL to 200 mg / mL, 50 mg / mL to 180 mg / mL, 50 mg / mL to 170 mg / mL, 50 mg / mL to 160 mg / mL, 50 mg / mL to 150 mg / mL, 50 mg / mL to 140 mg / mL, 50 mg / mL to 130 mg / mL, 50 mg / mL to 120 mg / mL, 50 mg / mL to 110 mg / mL, 50 mg / mL to 100 mg / mL, 50 mg / mL to 90 mg / mL, 50 mg / mL to 80 mg / mL, 50 mg / mL to 70 mg / mL, 50 mg / mL to 60 mg / mL, 75 mg / mL to 220 mg / mL, 75 mg / mL to 200 mg / mL, 75 mg / mL to 180 mg / mL, 75 mg / mL to 170 mg / mL, 75 mg / mL to 160 mg / mL, 75 mg / mL to 150 mg / mL, 75 mg / mL to 140 mg / mL, 75 mg / mL to 130 mg / mL, 75 mg / mL to 120 mg / mL, 75 mg / mL to 110 mg / mL, 75 mg / mL to 100 mg / mL, 75 mg / mL to 90 mg / mL, 75 mg / mL to 80 mg / mL, 100 mg / mL to 220 mg / mL, 100 mg / mL to 200 mg / mL, 100 mg / mL to 180 mg / mL, 100 mg / mL to 170 mg / mL, 100 mg / mL to 160 mg / mL, 100 mg / mL to 150 mg / mL, 100 mg / mL to 140 mg / mL, 100 mg / mL to 130 mg / mL, 100 mg / mL to 120 mg / mL, 100 mg / mL to 110 mg / mL, 100 mg / mL to 100 mg / mL, 100 mg / mL to 90 mg / mL, 150 mg / mL to 220 mg / mL, 150 mg / mL to 200 mg / mL, 150 mg / mL to 180 mg / mL, 150 mg / mL to 170 mg / mL, 150 mg / mL to 160 mg / mL, 175 mg / mL to 220 mg / mL, 175 mg / mL to 200 mg / mL, or 200 mg / mL to 220 mg / mL) of the combination of polyethylene glycol with propylene glycol.

[0137] Polysorbate 80

[0138] In certain embodiments, the liquid carrier comprises polysorbate 80. In some embodiments, the liquid carrier comprises 0.1% to 10% (w / w) polysorbate 80. In certain embodiments, the liquid carrier comprises 0.2% to 8% (w / w), 0.2% to 5% (w / w), 0.5% to 3% (w / w), or about 1% (w / w) polysorbate 80.

[0139] In certain embodiments, the liquid carrier comprises polyoxyethylene (20) sorbitan monooleate (polysorbate 80). In certain embodiments, the liquid carrier comprises 1 mg / mL to 50 mg / mL (e.g., 1 mg / mL to 40 mg / mL, 1 mg / mL to 30 mg / mL, 1 mg / mL to 25 mg / mL, 1 mg / mL to 20 mg / mL, 1 mg / mL to 15 mg / mL, 1 mg / mL to 10 mg / mL, 1 mg / mL to 5 mg / mL, 2 mg / mL to 50 mg / mL, 2 mg / mL to 40 mg / mL, 2 mg / mL to 30 mg / mL, 2 mg / mL to 25 mg / mL, 2 mg / mL to 20 mg / mL, 2 mg / mL to 15 mg / mL, 2 mg / mL to 10 mg / mL, 2 mg / mL to 5 mg / mL, 3 mg / mL to 50 mg / mL, 3 mg / mL to 40 mg / mL, 3 mg / mL to 30 mg / mL, 3 mg / mL to 25 mg / mL, 3 mg / mL to 20 mg / mL, 3 mg / mL to 15 mg / mL, 3 mg / mL to 10 mg / mL, 3 mg / mL to 5 mg / mL, 4 mg / mL to 50 mg / mL, 4 mg / mL to 40 mg / mL, 4 mg / mL to 30 mg / mL, 4 mg / mL to 25 mg / mL, 4 mg / mL to 20 mg / mL, 4 mg / mL to 15 mg / mL, 4 mg / mL to 10 mg / mL, 4 mg / mL to 5 mg / mL, 5 mg / mL to 50 mg / mL, 5 mg / mL to 40 mg / mL, 5 mg / mL to 30 mg / mL, 5 mg / mL to 25 mg / mL, 5 mg / mL to 20 mg / mL, 5 mg / mL to 15 mg / mL, 5 mg / mL to 10 mg / mL, 10 mg / mL to 50 mg / mL, 10 mg / mL to 40 mg / mL, 10 mg / mL to 30 mg / mL, 10 mg / mL to 25 mg / mL, 10 mg / mL to 20 mg / mL, 10 mg / mL to 15 mg / mL, 15 mg / mL to 50 mg / mL, 15 mg / mL to 40 mg / mL, 15 mg / mL to 30 mg / mL, 15 mg / mL to 25 mg / mL, 15 mg / mL to 20 mg / mL, 20 mg / mL to 50 mg / mL, 20 mg / mL to 40 mg / mL, 20 mg / mL to 30 mg / mL, 20 mg / mL to 25 mg / mL, 25 mg / mL to 50 mg / mL, 25 mg / mL to 40 mg / mL, 25 mg / mL to 30 mg / mL, 30 mg / mL to 50 mg / mL, 30 mg / mL to 40 mg / mL, or 40 mg / mL to 50 mg / mL) of polysorbate 80. In certain embodiments, the liquid carrier comprises 5 mg / ml to 20 mg / ml e.g., 8 mg / ml to 15 mg / ml of polysorbate 80.

[0140] In certain embodiments, the liquid carrier comprises a combination of the following: disodium or tetrasodium EDTA, propylene glycol or polyethylene glycol or combinations of both, and polysorbate 80. In certain embodiments, the liquid carrier comprises 1 mg / mL to 500 mg / mL (e.g., 10 mg / mL to 250 mg / mL, 10 mg / mL to 150 mg / mL, 30 mg / mL to 150 mg / mL, 50 mg / mL to 150 mg / mL, or 50 mg / mL to 100 mg / mL) of polyethylene glycol or propylene glycol, and 1 mg / mL to 50 mg / mL (e.g., 1 mg / mL to 25 mg / mL, 1 mg / mL to 15 mg / mL, 3 mg / mL to 15 mg / mL, 5 mg / mL to 15 mg / mL, or 5 mg / mL to 10 mg / mL) of polysorbate 80.

[0141] Further Therapeutic Agents

[0142] Levetiracetam

[0143] The composition may include one or more additional therapeutic agents (i.e., in addition to atorvastatin or salt thereof (e.g., atorvastatin calcium)).

[0144] In certain preferred embodiments, the composition includes levetiracetam. In some embodiments, the composition comprises 5 mg / mL to 500 mg / mL (e.g., 5 mg / mL to 400 mg / mL, 5 mg / mL to 300 mg / mL, 5 mg / mL to 250 mg / mL, 5 mg / mL to 200 mg / mL, 5 mg / mL to 150 mg / mL, 5 mg / mL to 100 mg / mL, 5 mg / mL to 75 mg / mL, 5 mg / mL to 60 mg / mL, 5 mg / mL to 50 mg / mL, 5 mg / mL to 30 mg / mL, 5 mg / mL to 25 mg / mL, 5 mg / mL to 10 mg / mL, 10 mg / mL to 500 mg / mL, 10 mg / mL to 400 mg / mL, 10 mg / mL to 300 mg / mL, 10 mg / mL to 250 mg / mL, 10 mg / mL to 200 mg / mL, 10 mg / mL to 150 mg / mL, 10 mg / mL to 100 mg / mL, 10 mg / mL to 75 mg / mL, 10 mg / mL to 60 mg / mL, 10 mg / mL to 50 mg / mL, 10 mg / mL to 30 mg / mL, 10 mg / mL to 25 mg / mL, 25 mg / mL to 500 mg / mL, 25 mg / mL to 400 mg / mL, 25 mg / mL to 300 mg / mL, 25 mg / mL to 250 mg / mL, 25 mg / mL to 200 mg / mL, 25 mg / mL to 150 mg / mL, 25 mg / mL to 100 mg / mL, 25 mg / mL to 75 mg / mL, 25 mg / mL to 60 mg / mL, 25 mg / mL to 50 mg / mL, 25 mg / mL to 30 mg / mL, 50 mg / mL to 500 mg / mL, 50 mg / mL to 400 mg / mL, 50 mg / mL to 300 mg / mL, 50 mg / mL to 250 mg / mL, 50 mg / mL to 200 mg / mL, 50 mg / mL to 150 mg / mL, 50 mg / mL to 100 mg / mL, 50 mg / mL to 75 mg / mL, 50 mg / mL to 60 mg / mL, 60 mg / mL to 500 mg / mL, 60 mg / mL to 400 mg / mL, 60 mg / mL to 300 mg / mL, 60 mg / mL to 250 mg / mL, 60 mg / mL to 200 mg / mL, 60 mg / mL to 150 mg / mL, 60 mg / mL to 100 mg / mL, 60 mg / mL to 75 mg / mL, 75 mg / mL to 500 mg / mL, 75 mg / mL to 400 mg / mL, 75 mg / mL to 300 mg / mL, 75 mg / mL to 250 mg / mL, 75 mg / mL to 200 mg / mL, 75 mg / mL to 150 mg / mL, 75 mg / mL to 100 mg / mL, 100 mg / mL to 500 mg / mL, 100 mg / mL to 400 mg / mL, 100 mg / mL to 300 mg / mL, 100 mg / mL to 250 mg / mL, 100 mg / mL to 200 mg / mL, 100 mg / mL to 150 mg / mL, 150 mg / mL to 500 mg / mL, 150 mg / mL to 400 mg / mL, 150 mg / mL to 300 mg / mL, 150 mg / mL to 250 mg / mL, 150 mg / mL to 200 mg / mL, 200 mg / mL to 500 mg / mL, 200 mg / mL to 400 mg / mL, 200 mg / mL to 300 mg / mL, 200 mg / mL to 250 mg / mL, 250 mg / mL to 500 mg / mL, 250 mg / mL to 400 mg / mL, 250 mg / mL to 300 mg / mL, 300 mg / mL to 500 mg / mL, 300 mg / mL to 400 mg / mL, or 400 mg / mL to 500 mg / mL) of levetiracetam.

[0145] In certain preferred embodiments, the composition comprises 5 mg / mL to 150 mg / mL (e.g., 5 mg / mL to 100 mg / mL, 5 mg / mL to 75 mg / mL, 5 mg / mL to 60 mg / mL, 5 mg / mL to 50 mg / mL, 5 mg / mL to 30 mg / mL, 5 mg / mL to 25 mg / mL, 5 mg / mL to 10 mg / mL, 10 mg / mL to 150 mg / mL, 10 mg / mL to 100 mg / mL, 10 mg / mL to 75 mg / mL, 10 mg / mL to 60 mg / mL, 10 mg / mL to 50 mg / mL, 10 mg / mL to 30 mg / mL, 10 mg / mL to 25 mg / mL, 25 mg / mL to 150 mg / mL, 25 mg / mL to 100 mg / mL, 25 mg / mL to 75 mg / mL, 25 mg / mL to 60 mg / mL, 25 mg / mL to 50 mg / mL, 25 mg / mL to 30 mg / mL, 50 mg / mL to 150 mg / mL, 50 mg / mL to 100 mg / mL, 50 mg / mL to 75 mg / mL, 50 mg / mL to 60 mg / mL, 60 mg / mL to 150 mg / mL, 60 mg / mL to 100 mg / mL, 60 mg / mL to 75 mg / mL, 75 mg / mL to 150 mg / mL, 75 mg / mL to 100 mg / mL, or 100 mg / mL to 150 mg / mL) of levetiracetam. In some more preferred embodiments, the composition includes 20 mg / mL to 150 mg / mL (e.g., 20 mg / mL to 120 mg / mL, 20 mg / mL to 100 mg / mL, 20 mg / mL to 60 mg / mL, 20 mg / mL to 50 mg / mL, 50 mg / mL to 150 mg / mL, 50 mg / mL to 120 mg / mL, 50 mg / mL to 100 mg / mL, 50 mg / mL to 60 mg / mL, 100 mg / mL to 150 mg / mL, 100 mg / mL to 120 mg / mL, or 120 mg / mL to 150 mg / mL) of levetiracetam. In yet more preferred embodiments, the composition includes 60 mg / mL to 120 mg / mL of levetiracetam. In some more preferred embodiments (e.g., for compositions configured for administration at a higher dosage volume (e.g., 40 mL to 50 mL)), the composition includes 30 mg / mL to 60 mg / mL of levetiracetam.

[0146] Brivaracetam

[0147] In some preferred embodiments, the composition includes brivaracetam. In some embodiments, the composition includes 0.5 mg / mL to 50 mg / mL (e.g., 0.5 mg / mL to 40 mg / mL, 0.5 mg / mL to 30 mg / mL, 0.5 mg / mL to 25 mg / mL, 0.5 mg / mL to 20 mg / mL, 0.5 mg / mL to 15 mg / mL, 0.5 mg / mL to 10 mg / mL, 0.5 mg / mL to 7.5 mg / mL, 0.5 mg / mL to 5 mg / mL, 0.5 mg / mL to 2.5 mg / mL, 2.5 mg / mL to 50 mg / mL, 2.5 mg / mL to 40 mg / mL, 2.5 mg / mL to 30 mg / mL, 2.5 mg / mL to 25 mg / mL, 2.5 mg / mL to 20 mg / mL, 2.5 mg / mL to 15 mg / mL, 2.5 mg / mL to 10 mg / mL, 2.5 mg / mL to 7.5 mg / mL, 2.5 mg / mL to 5 mg / mL, 5 mg / mL to 50 mg / mL, 5 mg / mL to 40 mg / mL, 5 mg / mL to 30 mg / mL, 5 mg / mL to 25 mg / mL, 5 mg / mL to 20 mg / mL, 5 mg / mL to 15 mg / mL, 5 mg / mL to 10 mg / mL, 5 mg / mL to 7.5 mg / mL, 7.5 mg / mL to 50 mg / mL, 7.5 mg / mL to 40 mg / mL, 7.5 mg / mL to 30 mg / mL, 7.5 mg / mL to 25 mg / mL, 7.5 mg / mL to 20 mg / mL, 7.5 mg / mL to 15 mg / mL, 7.5 mg / mL to 10 mg / mL, 10 mg / mL to 50 mg / mL, 10 mg / mL to 40 mg / mL, 10 mg / mL to 30 mg / mL, 10 mg / mL to 25 mg / mL, 10 mg / mL to 20 mg / mL, 10 mg / mL to 15 mg / mL, 15 mg / mL to 50 mg / mL, 15 mg / mL to 40 mg / mL, 15 mg / mL to 30 mg / mL, 15 mg / mL to 25 mg / mL, 15 mg / mL to 20 mg / mL, 20 mg / mL to 50 mg / mL, 20 mg / mL to 40 mg / mL, 20 mg / mL to 30 mg / mL, 20 mg / mL to 25 mg / mL, 25 mg / mL to 50 mg / mL, 25 mg / mL to 40 mg / mL, 25 mg / mL to 30 mg / mL, 30 mg / mL to 50 mg / mL, 30 mg / mL to 40 mg / mL, or 40 mg / mL to 50 mg / mL) of brivaracetam. In certain preferred embodiments, the composition includes 0.5 mg / mL to 10 mg / mL (e.g., 0.5 mg / mL to 7.5 mg / mL, 0.5 mg / mL to 5 mg / mL, 0.5 mg / mL to 2.5 mg / mL, 2.5 mg / mL to 10 mg / mL, 2.5 mg / mL to 7.5 mg / mL, 2.5 mg / mL to 5 mg / mL, 5 mg / mL to 10 mg / mL, 5 mg / mL to 7.5 mg / mL, or 7.5 mg / mL to 10 mg / mL) of brivaracetam. In yet more preferred embodiments, the composition includes 2 mg / mL to 8 mg / mL of brivaracetam. In still more preferred embodiments, the composition includes 4 mg / mL to 8 mg / mL of brivaracetam. In some more preferred embodiments (e.g., for compositions configured for administration at a higher dosage volume (e.g., 40 mL to 50 mL)), the composition includes 2 mg / mL to 4 mg / mL of brivaracetam.

[0148] Seletracetam In some preferred embodiments, the composition includes seletracetam. In some embodiments, the composition includes 0.25 mg / mL to 50 mg / mL (e.g., 0.25 mg / mL to 40 mg / mL, 0.25 mg / mL to 30 mg / mL, 0.25 mg / mL to 25 mg / mL, 0.25 mg / mL to 20 mg / mL, 0.25 mg / mL to 15 mg / mL, 0.25 mg / mL to 10 mg / mL, 0.25 mg / mL to 7.5 mg / mL, 0.25 mg / mL to 5 mg / mL, 0.25 mg / mL to 2.5 mg / mL, 0.5 mg / mL to 50 mg / mL (e.g., 0.5 mg / mL to 40 mg / mL, 0.5 mg / mL to 30 mg / mL, 0.5 mg / mL to 25 mg / mL, 0.5 mg / mL to 20 mg / mL, 0.5 mg / mL to 15 mg / mL, 0.5 mg / mL to 10 mg / mL, 0.5 mg / mL to 7.5 mg / mL, 0.5 mg / mL to 5 mg / mL, 0.5 mg / mL to 2.5 mg / mL, 2.5 mg / mL to 50 mg / mL, 2.5 mg / mL to 40 mg / mL, 2.5 mg / mL to 30 mg / mL, 2.5 mg / mL to 25 mg / mL, 2.5 mg / mL to 20 mg / mL, 2.5 mg / mL to 15 mg / mL, 2.5 mg / mL to 10 mg / mL, 2.5 mg / mL to 7.5 mg / mL, 2.5 mg / mL to 5 mg / mL, 5 mg / mL to 50 mg / mL, 5 mg / mL to 40 mg / mL, 5 mg / mL to 30 mg / mL, 5 mg / mL to 25 mg / mL, 5 mg / mL to 20 mg / mL, 5 mg / mL to 15 mg / mL, 5 mg / mL to 10 mg / mL, 5 mg / mL to 7.5 mg / mL, 7.5 mg / mL to 50 mg / mL, 7.5 mg / mL to 40 mg / mL, 7.5 mg / mL to 30 mg / mL, 7.5 mg / mL to 25 mg / mL, 7.5 mg / mL to 20 mg / mL, 7.5 mg / mL to 15 mg / mL, 7.5 mg / mL to 10 mg / mL, 10 mg / mL to 50 mg / mL, 10 mg / mL to 40 mg / mL, 10 mg / mL to 30 mg / mL, 10 mg / mL to 25 mg / mL, 10 mg / mL to 20 mg / mL, 10 mg / mL to 15 mg / mL, 15 mg / mL to 50 mg / mL, 15 mg / mL to 40 mg / mL, 15 mg / mL to 30 mg / mL, 15 mg / mL to 25 mg / mL, 15 mg / mL to 20 mg / mL, 20 mg / mL to 50 mg / mL, 20 mg / mL to 40 mg / mL, 20 mg / mL to 30 mg / mL, 20 mg / mL to 25 mg / mL, 25 mg / mL to 50 mg / mL, 25 mg / mL to 40 mg / mL, 25 mg / mL to 30 mg / mL, 30 mg / mL to 50 mg / mL, 30 mg / mL to 40 mg / mL, or 40 mg / mL to 50 mg / mL) of seletracetam. In certain preferred embodiments, the composition includes 0.25 mg / mL to 10 mg / mL (e.g., 0.25 mg / mL to 7.5 mg / mL, 0.25 mg / mL to 5 mg / mL, 0.25 mg / mL to 2.5 mg / mL, 2.5 mg / mL to 10 mg / mL, 2.5 mg / mL to 7.5 mg / mL, 2.5 mg / mL to 5 mg / mL, 5 mg / mL to 10 mg / mL, 5 mg / mL to 7.5 mg / mL, or 7.5 mg / mL to 10 mg / mL) of seletracetam. In yet more preferred embodiments, the composition includes 1 mg / mL to 8 mg / mL of seletracetam. In still more preferred embodiments, the composition includes 2 mg / mL to 8 mg / mL of seletracetam. In some more preferred embodiments (e.g., for compositions configured for administration at a higher dosage volume (e.g., 40 mL to 50 mL)), the composition includes 1 mg / mL to 4 mg / mL of brivaracetam. Ceftriaxone

[0149] In some preferred embodiments, the composition further includes ceftriaxone. In certain embodiments, the composition includes 5 mg / mL to 500 mg / mL (e.g., 5 mg / mL to 400 mg / mL, 5 mg / mL to 300 mg / mL, 5 mg / mL to 250 mg / mL, 5 mg / mL to 200 mg / mL, 5 mg / mL to 150 mg / mL, 5 mg / mL to 100 mg / mL, 5 mg / mL to 75 mg / mL, 5 mg / mL to 60 mg / mL, 5 mg / mL to 50 mg / mL, 5 mg / mL to 30 mg / mL, 5 mg / mL to 25 mg / mL, 5 mg / mL to 10 mg / mL, 10 mg / mL to 500 mg / mL, 10 mg / mL to 400 mg / mL, 10 mg / mL to 300 mg / mL, 10 mg / mL to 250 mg / mL, 10 mg / mL to 200 mg / mL, 10 mg / mL to 150 mg / mL, 10 mg / mL to 100 mg / mL, 10 mg / mL to 75 mg / mL, 10 mg / mL to 60 mg / mL, 10 mg / mL to 50 mg / mL, 10 mg / mL to 30 mg / mL, 10 mg / mL to 25 mg / mL, 25 mg / mL to 500 mg / mL, 25 mg / mL to 400 mg / mL, 25 mg / mL to 300 mg / mL, 25 mg / mL to 250 mg / mL, 25 mg / mL to 200 mg / mL, 25 mg / mL to 150 mg / mL, 25 mg / mL to 100 mg / mL, 25 mg / mL to 75 mg / mL, 25 mg / mL to 60 mg / mL, 25 mg / mL to 50 mg / mL, 25 mg / mL to 30 mg / mL, 50 mg / mL to 500 mg / mL, 50 mg / mL to 400 mg / mL, 50 mg / mL to 300 mg / mL, 50 mg / mL to 250 mg / mL, 50 mg / mL to 200 mg / mL, 50 mg / mL to 150 mg / mL, 50 mg / mL to 100 mg / mL, 50 mg / mL to 75 mg / mL, 50 mg / mL to 60 mg / mL, 60 mg / mL to 500 mg / mL, 60 mg / mL to 400 mg / mL, 60 mg / mL to 300 mg / mL, 60 mg / mL to 250 mg / mL, 60 mg / mL to 200 mg / mL, 60 mg / mL to 150 mg / mL, 60 mg / mL to 100 mg / mL, 60 mg / mL to 75 mg / mL, 75 mg / mL to 500 mg / mL, 75 mg / mL to 400 mg / mL, 75 mg / mL to 300 mg / mL, 75 mg / mL to 250 mg / mL, 75 mg / mL to 200 mg / mL, 75 mg / mL to 150 mg / mL, 75 mg / mL to 100 mg / mL, 100 mg / mL to 500 mg / mL, 100 mg / mL to 400 mg / mL, 100 mg / mL to 300 mg / mL, 100 mg / mL to 250 mg / mL, 100 mg / mL to 200 mg / mL, 100 mg / mL to 150 mg / mL, 150 mg / mL to 500 mg / mL, 150 mg / mL to 400 mg / mL, 150 mg / mL to 300 mg / mL, 150 mg / mL to 250 mg / mL, 150 mg / mL to 200 mg / mL, 200 mg / mL to 500 mg / mL, 200 mg / mL to 400 mg / mL, 200 mg / mL to 300 mg / mL, 200 mg / mL to 250 mg / mL, 250 mg / mL to 500 mg / mL, 250 mg / mL to 400 mg / mL, 250 mg / mL to 300 mg / mL, 300 mg / mL to 500 mg / mL, 300 mg / mL to 400 mg / mL, or 400 mg / mL to 500 mg / mL) of ceftriaxone.

[0150] In certain preferred embodiments, the composition includes 5 mg / mL to 150 mg / mL (e.g., 5 mg / mL to 100 mg / mL, 5 mg / mL to 75 mg / mL, 5 mg / mL to 60 mg / mL, 5 mg / mL to 50 mg / mL, 5 mg / mL to 30 mg / mL, 5 mg / mL to 25 mg / mL, 5 mg / mL to 10 mg / mL, 10 mg / mL to 150 mg / mL, 10 mg / mL to 100 mg / mL, 10 mg / mL to 75 mg / mL, 10 mg / mL to 60 mg / mL, 10 mg / mL to 50 mg / mL, 10 mg / mL to 30 mg / mL, 10 mg / mL to 25 mg / mL, 25 mg / mL to 150 mg / mL, 25 mg / mL to 100 mg / mL, 25 mg / mL to 75 mg / mL, 25 mg / mL to 60 mg / mL, 25 mg / mL to 50 mg / mL, 25 mg / mL to 30 mg / mL, 50 mg / mL to 150 mg / mL, 50 mg / mL to 100 mg / mL, 50 mg / mL to 75 mg / mL, 50 mg / mL to 60 mg / mL, 60 mg / mL to 150 mg / mL, 60 mg / mL to 100 mg / mL, 60 mg / mL to 75 mg / mL, 75 mg / mL to 150 mg / mL, 75 mg / mL to 100 mg / mL, or 100 mg / mL to 150 mg / mL) of levetiracetam. In some more preferred embodiments, the composition includes 20 mg / mL to 150 mg / mL (e.g., 20 mg / mL to 120 mg / mL, 20 mg / mL to 100 mg / mL, 20 mg / mL to 60 mg / mL, 20 mg / mL to 50 mg / mL, 50 mg / mL to 150 mg / mL, 50 mg / mL to 120 mg / mL, 50 mg / mL to 100 mg / mL, 50 mg / mL to 60 mg / mL, 100 mg / mL to 150 mg / mL, 100 mg / mL to 120 mg / mL, or 120 mg / mL to 150 mg / mL) of ceftriaxone. In yet more preferred embodiments, the composition includes 60 mg / mL to 120 mg / mL of ceftriaxone. In some more preferred embodiments (e.g., for compositions configured for administration at a higher dosage volume (e.g., 40 mL to 50 mL)), the composition includes 30 mg / mL to 60 mg / mL of ceftriaxone.

[0151] In some preferred embodiments, the composition further includes clavulanic acid or a pharmaceutically acceptable salt.

[0152] In some embodiments, the composition includes 5 mg / mL to 500 mg / mL (e.g., 5 mg / mL to 400 mg / mL, 5 mg / mL to 300 mg / mL, 5 mg / mL to 250 mg / mL, 5 mg / mL to 200 mg / mL, 5 mg / mL to 150 mg / mL, 5 mg / mL to 100 mg / mL, 5 mg / mL to 75 mg / mL, 5 mg / mL to 60 mg / mL, 5 mg / mL to 50 mg / mL, 5 mg / mL to 30 mg / mL, 5 mg / mL to 25 mg / mL, 5 mg / mL to 10 mg / mL, 10 mg / mL to 500 mg / mL, 10 mg / mL to 400 mg / mL, 10 mg / mL to 300 mg / mL, 10 mg / mL to 250 mg / mL, 10 mg / mL to 200 mg / mL, 10 mg / mL to 150 mg / mL, 10 mg / mL to 100 mg / mL, 10 mg / mL to 75 mg / mL, 10 mg / mL to 60 mg / mL, 10 mg / mL to 50 mg / mL, 10 mg / mL to 30 mg / mL, 10 mg / mL to 25 mg / mL, 25 mg / mL to 500 mg / mL, 25 mg / mL to 400 mg / mL, 25 mg / mL to 300 mg / mL, 25 mg / mL to 250 mg / mL, 25 mg / mL to 200 mg / mL, 25 mg / mL to 150 mg / mL, 25 mg / mL to 100 mg / mL, 25 mg / mL to 75 mg / mL, 25 mg / mL to 60 mg / mL, 25 mg / mL to 50 mg / mL, 25 mg / mL to 30 mg / mL, 50 mg / mL to 500 mg / mL, 50 mg / mL to 400 mg / mL, 50 mg / mL to 300 mg / mL, 50 mg / mL to 250 mg / mL, 50 mg / mL to 200 mg / mL, 50 mg / mL to 150 mg / mL, 50 mg / mL to 100 mg / mL, 50 mg / mL to 75 mg / mL, 50 mg / mL to 60 mg / mL, 60 mg / mL to 500 mg / mL, 60 mg / mL to 400 mg / mL, 60 mg / mL to 300 mg / mL, 60 mg / mL to 250 mg / mL, 60 mg / mL to 200 mg / mL, 60 mg / mL to 150 mg / mL, 60 mg / mL to 100 mg / mL, 60 mg / mL to 75 mg / mL, 75 mg / mL to 500 mg / mL, 75 mg / mL to 400 mg / mL, 75 mg / mL to 300 mg / mL, 75 mg / mL to 250 mg / mL, 75 mg / mL to 200 mg / mL, 75 mg / mL to 150 mg / mL, 75 mg / mL to 100 mg / mL, 100 mg / mL to 500 mg / mL, 100 mg / mL to 400 mg / mL, 100 mg / mL to 300 mg / mL, 100 mg / mL to 250 mg / mL, 100 mg / mL to 200 mg / mL, 100 mg / mL to 150 mg / mL, 150 mg / mL to 500 mg / mL, 150 mg / mL to 400 mg / mL, 150 mg / mL to 300 mg / mL, 150 mg / mL to 250 mg / mL, 150 mg / mL to 200 mg / mL, 200 mg / mL to 500 mg / mL, 200 mg / mL to 400 mg / mL, 200 mg / mL to 300 mg / mL, 200 mg / mL to 250 mg / mL, 250 mg / mL to 500 mg / mL, 250 mg / mL to 400 mg / mL, 250 mg / mL to 300 mg / mL, 300 mg / mL to 500 mg / mL, 300 mg / mL to 400 mg / mL, or 400 mg / mL to 500 mg / mL) of clavulanate (clavulanic acid salt).

[0153] In certain preferred embodiments, the composition includes 5 mg / mL to 150 mg / mL (e.g., 5 mg / mL to 100 mg / mL, 5 mg / mL to 75 mg / mL, 5 mg / mL to 60 mg / mL, 5 mg / mL to 50 mg / mL, 5 mg / mL to 30 mg / mL, 5 mg / mL to 25 mg / mL, 5 mg / mL to 10 mg / mL, 10 mg / mL to 150 mg / mL, 10 mg / mL to 100 mg / mL, 10 mg / mL to 75 mg / mL, 10 mg / mL to 60 mg / mL, 10 mg / mL to 50 mg / mL, 10 mg / mL to 30 mg / mL, 10 mg / mL to 25 mg / mL, 25 mg / mL to 150 mg / mL, 25 mg / mL to 100 mg / mL, 25 mg / mL to 75 mg / mL, 25 mg / mL to 60 mg / mL, 25 mg / mL to 50 mg / mL, 25 mg / mL to 30 mg / mL, 50 mg / mL to 150 mg / mL, 50 mg / mL to 100 mg / mL, 50 mg / mL to 75 mg / mL, 50 mg / mL to 60 mg / mL, 60 mg / mL to 150 mg / mL, 60 mg / mL to 100 mg / mL, 60 mg / mL to 75 mg / mL, 75 mg / mL to 150 mg / mL, 75 mg / mL to 100 mg / mL, or 100 mg / mL to 150 mg / mL) of levetiracetam. In some more preferred embodiments, the composition includes 20 mg / mL to 150 mg / mL (e.g., 20 mg / mL to 120 mg / mL, 20 mg / mL to 100 mg / mL, 20 mg / mL to 60 mg / mL, 20 mg / mL to 50 mg / mL, 50 mg / mL to 150 mg / mL, 50 mg / mL to 120 mg / mL, 50 mg / mL to 100 mg / mL, 50 mg / mL to 60 mg / mL, 100 mg / mL to 150 mg / mL, 100 mg / mL to 120 mg / mL, or 120 mg / mL to 150 mg / mL) of ceftriaxone. In yet more preferred embodiments, the composition includes 60 mg / mL to 120 mg / mL of ceftriaxone. In some more preferred embodiments (e.g., for compositions configured for administration at a higher dosage volume (e.g., 40 mL to 50 mL)), the composition includes 30 mg / mL to 60 mg / mL of clavulanate (clavulanic acid salt).

[0154] Excipients

[0155] The pharmaceutical compositions disclosed herein may further include one or more pharmaceutically acceptable excipients, e.g., an antioxidant, an emulsifier, a tonicity agent, an acidulant, or a combination thereof. Other pharmaceutically acceptable excipients can be colorants, flavoring agents, sweeteners, taste masking agent, thickening agents, and the like. In certain embodiments, the compositions described herein do not include an antioxidant. In some embodiments, the compositions described herein do not include ascorbic acid, sodium metabisulfite, or potassium metabisulfite.

[0156] Antioxidants are pharmaceutically acceptable excipients, typically utilized for their capability to reduce oxidation-related decomposition of a pharmaceutical composition ingredient. Non-limiting examples of antioxidants include citric acid, a-tocopherol (e.g., D,L-a-tocopherol), monothioglycerol, ascorbic acid, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), sodium sulfite, sodium bisulfite, sodium thiosulfate, p-amino benzoic acid, glutathione, propyl gallate, and combinations thereof. Pharmaceutical compositions disclosed herein may include, e.g., 0.001% (w / v) to 1% (w / v) (e.g., 0.01% (w / v) to 0.5% (w / v)) of an antioxidant, which is preferably selected from antioxidants that do not degrade atorvastatin (e.g., ascorbic acid, sodium metabisulfite, or potassium metabisulfite).

[0157] Emulsifiers are pharmaceutically acceptable excipients that may be used to stabilize pharmaceutical compositions, e.g., against mechanical stresses like agitation, shearing and / or crystallization. Non-limiting examples of pharmaceutically acceptable emulsifiers include poloxamers (e.g., low molecular weight poloxamers (e.g., poloxamers having an average molecular weight of less than 10 kDa, e.g., poloxamer 188), polysorbates, polyoxyethylene alkyl ethers (Brij), alkylphenylpolyoxyethylene ethers (Triton-X), sodium dodecyl sulphate (SDS), polyvinylpyrrolidone (PVP), 1 ,2-propylene glycol, cremophor EL, cremophor RH40, lecithin, tert-butanol, ethanol, or polyoxyethylene stearate. In certain preferred embodiments, the emulsifier is a polysorbate. The pharmaceutical compositions disclosed herein may include, e.g., 0.0001% (w / v) to 5% (w / v) (e.g., 0.001% (w / v) to 4% (w / v), 0.001% (w / v) to 3% (w / v), 0.001% (w / v) to 2% (w / v), 0.001% (w / v) to 1% (w / v), 0.001% (w / v) to 0.5% (w / v), 0.001% (w / v) to 0.3% (w / v), 0.001% (w / v) to 0.1% (w / v), 0.003% (w / v) to 5% (w / v), 0.003% (w / v) to 4% (w / v), 0.003% (w / v) to 3% (w / v), 0.003% (w / v) to 2% (w / v), 0.003% (w / v) to 1% (w / v), 0.003% (w / v) to 0.5% (w / v), 0.003% (w / v) to 0.3% (w / v), 0.003% (w / v) to 0.1% (w / v), 0.1% (w / v) to 5% (w / v), 0.1% (w / v) to 4% (w / v), 0.1% (w / v) to 3% (w / v), 0.1% (w / v) to 2% (w / v), 0.1% (w / v) to 1% (w / v), 0.1% (w / v) to 0.5% (w / v), 0.1% (w / v) to 0.3% (w / v), 0.3% (w / v) to 5% (w / v), 0.3% (w / v) to 4% (w / v), 0.3% (w / v) to 3% (w / v), 0.3% (w / v) to 2% (w / v), 0.3% (w / v) to 1% (w / v), 0.3% (w / v) to 0.5% (w / v), 0.5% (w / v) to 5% (w / v), 0.5% (w / v) to 4% (w / v), 0.5% (w / v) to 3% (w / v), 0.5% (w / v) to 2% (w / v), 0.5% (w / v) to 1% (w / v), 1% (w / v) to 5% (w / v), 1% (w / v) to 4% (w / v), 1% (w / v) to 3% (w / v), 1% (w / v) to 2% (w / v), 2% (w / v) to 5% (w / v), 2% (w / v) to 4% (w / v), 2% (w / v) to 3% (w / v), 3% (w / v) to 5% (w / v), 3% (w / v) to 4% (w / v), or 4% (w / v) to 5% (w / v)) of an emulsifier. In some embodiments, the composition disclosed herein (e.g., those including propylene glycol, tert-butanol, ethanol, or a combination thereof as an emulsifier) may include, e.g., 1% (w / v) to 40% (w / v) (e.g., 1% (w / v) to 15% (w / v)) of an emulsifier. In some embodiments, the composition disclosed herein includes, e.g., 1% (w / v) to 15% (w / v) of an emulsifier.

[0158] Tonicity agents are pharmaceutically acceptable excipients, typically utilized to modulate the tonicity of a liquid pharmaceutical composition. Tonicity in general relates to the osmotic pressure of a solution and is typically assessed relative to that of human blood serum. In some embodiments, the composition disclosed herein is hypotonic, isotonic, or hypertonic. In certain preferred embodiments, the composition is isotonic. An isotonic solution is a liquid having the same tonicity as a reference solution, e.g., an isotonic saline or the blood serum. Non-limiting examples of tonicity agents include pharmaceutically acceptable salts (e.g., alkaline salts, e.g., alkaline halides (e.g., sodium chloride and / or potassium chloride), amino acids, and sugars. In some preferred embodiments, the tonicity agent is sodium chloride, trehalose, sucrose, or arginine. Non-limiting examples of amino acid tonicity agents include arginine, glycine, ornithine, lysine, histidine, glutamic acid, aspartic acid, isoleucine, leucine, alanine, phenylalanine, tyrosine, tryptophan, methionine, serine, and proline.

[0159] Acidulants are pharmaceutically acceptable excipients, typically utilized to modulate the pH of a liquid pharmaceutical composition. In some embodiments, the composition includes a sufficient amount of an acidulant to have a pH 5.5 to 8.8. In some preferred embodiments, the pH range is 6.5 to 8.5. In some embodiments, the acidulant is a weak BrOnsted acids, e.g., acids having a pKa of 3-8. Non-limiting examples of acidulants include acetic acid, maleic acid, ascorbic acid, lactic acid, malic acid, and phosphoric acid.

[0160] Administration

[0161] In some embodiments, the pharmaceutical composition disclosed herein is for parenteral administration, e.g., intravenous, intraperitoneal, subcutaneous, intramuscular, or intrathecal mode of administration. Parenteral administration may be by continuous infusion over a predetermined period of time. In some embodiments, the composition disclosed herein is for oral administration.

[0162] The pharmaceutical compositions, e.g., for parenteral administration, may be provided in one or more containers. Such container may be, e.g., vial, bottle, ampoule, or another pharmaceutically acceptable container. In some embodiments, the container may be a prefilled dosing system, e.g., a prefilled syringe, a prefilled infusion bottle, or a prefilled infusion bag.

[0163] In certain embodiments, pharmaceutical compositions disclosed herein may be prepared shortly before administration (e.g., at the point-of-use or to be used within, e.g., 24 to 48 hours of preparation). Such pharmaceutical compositions may be prepared using kits disclosed herein. Typically, a kit disclosed herein includes a first container and a second container, the first container including atorvastatin or salt thereof (e.g., atorvastatin or salt thereof as the only therapeutic agent; atorvastatin or salt thereof and levetiracetam; atorvastatin or salt thereof and brivaracetam; atorvastatin or salt thereof and seletracetam; atorvastatin or salt thereof, levetiracetam, and ceftriaxone or clavulanate; atorvastatin or salt thereof, seletracetam, and ceftriaxone or clavulanate; or atorvastatin or salt thereof, brivaracetam, and ceftriaxone or clavulanate) or pharmaceutically acceptable salts thereof, and the second container including a pharmaceutically acceptable aqueous solution of tetrasodium or disodium-EDTA, proyolene glycol or polyethylene glycol, and polysorbate 80. Kits disclosed herein are configured to provide a pharmaceutical composition disclosed herein.

[0164] Liquid pharmaceutical composition disclosed herein may be used in a method of treating a patient in need thereof. The method includes administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein. The pharmaceutical composition may be prepared from a kit. Thus, the method may include combining the first container contents and the second container contents in the kit described herein to produce a pharmaceutical composition, and administering a therapeutically effective amount of the pharmaceutical composition to the patient.

[0165] The therapeutically effective amount may be an amount providing, e.g., 0.1 mg / kg / day to 5 mg / kg / day (e.g., 0.1 mg / kg / day to 2 mg / kg / day) of atorvastatin or salt thereof. For example, the therapeutically effective amount may be, e.g., an amount providing at least 5 mg / day (e.g., at least 10 mg / day) of atorvastatin or salt thereof. Additionally or alternatively, the therapeutically effective amount may be, e.g., an amount providing 250 mg / day or less (e.g., 150 mg / day or less) of atorvastatin or salt thereof. The therapeutically effective amount may be an amount providing, e.g., 2.5 mg / kg / day to 150 mg / kg / day (e.g., 10 mg / kg / day to 75 mg / kg / day) of levetiracetam. The therapeutically effective amount may be an amount providing, e.g., 0.2 mg / kg / day to 10 mg / kg / day (e.g., 0.5 mg / kg / day to 5 mg / kg / day) of brivaracetam. The therapeutically effective amount may be an amount providing, e.g., 0.1 mg / kg / day to 10 mg / kg / day (e.g., 0.25 mg / kg / day to 5 mg / kg / day) of seletracetam. Additionally or alternatively, the therapeutically effective amount may be, e.g., an amount providing 50 mg / day to 400 mg / day (e.g., 50 mg / day to 200 mg / day or 100 mg / day to 400 mg / day) of brivaracetam. Additionally or alternatively, the therapeutically effective amount may be, e.g., an amount providing 25 mg / day to 400 mg / day (e.g., 25 mg / day to 200 mg / day or 50 mg / day to 200 mg / day) of seletracetam. The therapeutically effective amount may be an amount providing, e.g., 2.5 mg / kg / day to 150 mg / kg / day (e.g., 10 mg / kg / day to 75 mg / kg / day) of ceftriaxone or clavulanate.

[0166] The pharmaceutical composition may be administered, e.g., parenterally (e.g., intravenously, subcutaneously, or intramuscularly). The pharmaceutical composition may be administered, e.g., orally.

[0167] In instances involving administration of a pharmaceutical composition including atorvastatin or salt thereof as the only therapeutic agent, the method may further include step(s) of administering (i) levetiracetam or brivaracetam or seletracetam and / or (ii) ceftriaxone or clavulanate a pharmaceutically acceptable salt thereof. Levetiracetam may be administered as the only additional therapeutic agent or in combination with ceftriaxone or a pharmaceutically acceptable salt thereof. When levetiracetam is administered in combination with ceftriaxone or a pharmaceutically acceptable salt thereof, the two therapeutic agents may be administered in the same pharmaceutical composition or in different pharmaceutical compositions. When levetiracetam is administered in combination with ceftriaxone or a pharmaceutically acceptable salt thereof, the two therapeutic agents may be administered by the same route of administration or by different routes of administration. A pharmaceutical composition including levetiracetam may be administered by the same route of administration as the pharmaceutical composition including atorvastatin or salt thereof. Alternatively, a pharmaceutical composition including levetiracetam may be administered by a different route of administration as the pharmaceutical composition including atorvastatin or salt thereof. Brivaracetam may be administered as the only additional therapeutic agent or in combination with ceftriaxone or a pharmaceutically acceptable salt thereof. When brivaracetam is administered in combination with ceftriaxone or a pharmaceutically acceptable salt thereof, the two therapeutic agents may be administered by the same route of administration or by different routes of administration. A pharmaceutical composition including brivaracetam may be administered by the same route of administration as the pharmaceutical composition including atorvastatin or salt thereof. Alternatively, a pharmaceutical composition including brivaracetam may be administered by a different route of administration as the pharmaceutical composition including atorvastatin or salt thereof.

[0168] Seletracetam may be administered as the only additional therapeutic agent or in combination with ceftriaxone or a pharmaceutically acceptable salt thereof. When seletracetam is administered in combination with ceftriaxone or a pharmaceutically acceptable salt thereof, the two therapeutic agents may be administered by the same route of administration or by different routes of administration. A pharmaceutical composition including seletracetam may be administered by the same route of administration as the pharmaceutical composition includingatorvastatin or salt thereof. Alternatively, a pharmaceutical composition including seletracetam may be administered by a different route of administration as the pharmaceutical composition including atorvastatin or salt thereof. A pharmaceutical composition including ceftriaxone or a pharmaceutically acceptable salt thereof may be administered by the same route of administration as the pharmaceutical composition including atorvastatin or salt thereof. Alternatively, a pharmaceutical composition including ceftriaxone or a pharmaceutically acceptable salt thereof may be administered by a different route of administration as the pharmaceutical composition including atorvastatin or salt thereof. Ceftriaxone may be replaced by clavulanate or any pharmaceutically acceptable salt thereof in all formulations.

[0169] In instances involving administration of a pharmaceutical composition including atorvastatin or salt thereof and levetiracetam as the only therapeutic agents, the method may further include step of administering ceftriaxone or a pharmaceutically acceptable salt thereof. A pharmaceutical composition including ceftriaxone or a pharmaceutically acceptable salt thereof may be administered by the same route of administration as the pharmaceutical composition including atorvastatin or salt thereof and levetiracetam. Alternatively, a pharmaceutical composition including ceftriaxone or a pharmaceutically acceptable salt thereof may be administered by a different route of administration as the pharmaceutical composition including atorvastatin or salt thereof and levetiracetam. In instances involving administration of a pharmaceutical composition including atorvastatin or salt thereof or a pharmaceutically acceptable salt thereof and brivaracetam or seletracetam as the only therapeutic agents, the method may further include step of administering ceftriaxone or a pharmaceutically acceptable salt thereof. A pharmaceutical composition including ceftriaxone or a pharmaceutically acceptable salt thereof may be administered by the same route of administration as the pharmaceutical composition including atorvastatin or salt thereof and brivaracetam or seletracetam. Alternatively, a pharmaceutical composition including ceftriaxone or a pharmaceutically acceptable salt thereof may be administered by a different route of administration as the pharmaceutical composition including atorvastatin or salt thereof and brivaracetam or seletracetam.

[0170] In instances involving administration of a pharmaceutical composition including atorvastatin or salt thereof and ceftriaxone or a pharmaceutically acceptable salt thereof as the only therapeutic agents, the method may further include step of administering levetiracetam or brivaracetam or seletracetam. A pharmaceutical composition including levetiracetam may be administered by the same route of administration as the pharmaceutical composition including atorvastatin or salt thereof and ceftriaxone or a pharmaceutically acceptable salt thereof. Alternatively, a pharmaceutical composition including levetiracetam may be administered by a different route of administration as the pharmaceutical composition including atorvastatin or salt thereof and ceftriaxone or a pharmaceutically acceptable salt thereof. A pharmaceutical composition including brivaracetam or seletracetam may be administered by the same route of administration as the pharmaceutical composition including atorvastatin or salt thereof and ceftriaxone or a pharmaceutically acceptable salt thereof. Alternatively, a pharmaceutical composition including brivaracetam or seletracetam may be administered by a different route of administration as the pharmaceutical composition including atorvastatin or salt thereof and ceftriaxone or a pharmaceutically acceptable salt thereof.

[0171] Treatment

[0172] The subject may be in need of a treatment for, e.g., epilepsy, seizures, anoxia, anoxia- induced brain injury, stroke, cardiac events (cardiac stroke, myocardial infarction), traumatic brain injury, brain infection, brain abscess, aneurism, subarachnoid haemorrhage, status epilepticus, refractory status epilepticus, refractory partial onset seizures (POS), gambling addiction, migraines, substance dependence, alcoholism, cocaine dependence, nicotine dependence, metabolic syndrome X, diabetes mellitus, type 2, vomiting, obsessive-compulsive disorder, refractory generalized social phobia, Tourette Syndrome, levodopa-induced dyskinesia in Parkinson's Disease, Prader-Willi syndrome, multiple sclerosis, Lennox- Gastaut Syndrome, Dravet's syndrome, bipolar disorder, obesity, post-traumatic stress disorder, cluster headaches, severe headaches, or a condition caused by exposure to a chemical warfare nerve agent. Preferably, the patient is in need of a treatment for cardiac events (cardiac stroke, myocardial infarction), post-traumatic epilepsy and post-traumatic epilepsy associated central nervous system symptoms, epilepsy, seizures, anoxia and anoxia induced brain injury, stroke, traumatic brain injury, brain infection, and subarachnoid hemorrhage, brain abscess, status epilepticus, refractory status epilepticus, or refractory partial onset seizures. The subject may be in need of, e.g., neuroprotection and, for cardiac stroke, for protection of the cardiac muscle to limit the size of the lesion. In some preferred embodiments, the subject is in need of a treatment for traumatic brain injury, stroke, cardiac stroke, or a brain infection. The subject may be in need of a treatment for, e.g., a brain abscess.

[0173] Each of the compounds may be, for example, administered to the patient in a single dose or in multiple doses. For any such combinations, the frequency of dosing may be the same for each of the compounds to be combined, or may be individually selected for each of the individual compounds to be combined. When multiple doses are administered, the doses may be separated from one another by, for example, 1-24 hours, or 1-7 days. The compound may be administered according to a schedule or the compound may be administered without a predetermined schedule. An active compound may be administered, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 times per day, every 2nd, 3rd, 4th, 5th, or 6th day, or 1, 2, 3, 4, 5, 6, or 7 times per week. In the case of parenteral administration, such as intravenous or subcutaneous administration, each compound or combination may be administered as bolus administration one or several times per day (1-12 times per day), or as slow bolus with each individual bolus administration taking 1 to 120 min, or as continuous infusion, without or with loading bolus administration. It is to be understood that, for any particular subject, specific dosage regimes should be adjusted over time according to the individual need and the professional judgment of the person administering or supervising the administration of the compositions. The time periods during which the therapeutic combination may be administered may be as described herein.

[0174] In some preferred embodiments, the treatment is to be administered within a defined time frame after the occurrence of the traumatic brain injury or the cardiac stroke. The initiation treatment with effective doses is initiated within less than 7 days after the brain insult, preferably within less than 48 or 24 h after the brain insult, and most preferably within less than 8 h after the brain insult. The initial treatment is continued for a period of 3 day to 3 months after the insult, preferably for 5-30 days. The initiation treatment may be followed by a continuation treatment with the same combination immediately thereafter, either by a different administration route or using the same administration route. Such prolonged treatment can be expected to continue after the initiation treatment for 3 to 6 months, or, if epileptogenesis is only ameliorated, may be administered chronically, to treat the remaining symptoms, as medically indicated, or until occurrence of uncontrolled seizures, which require a change in treatment regimen.

[0175] Preparation

[0176] When the excipient serves as a diluent, it can be a solid, semisolid, or liquid material (e.g., isotonic saline or aqueous solution containing the excipients including propylene glycol or polyethylene glycol, polyorbate 80 and meglumine or a selection of these excipients), which acts as a vehicle, carrier, or medium for the therapeutic agent.

[0177] The pharmaceutical forms suitable for injectable use include sterile aqueous solutions (where water soluble) or sterile powders for the extemporaneous preparation of sterile injectable solutions. In all cases, the form must be sterile and must be fluid to the extent that easy syringability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), suitable mixtures thereof, and vegetable oils. The proper fluidity can be maintained, for example, using emulsifiers. The prevention of the action of microorganisms can be brought about by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, thimerosal, and the like. In many cases, it will be preferable to include a tonicity agent, for example, a sugar or sodium chloride. Prolonged absorption of the injectable compositions can be brought about by the use in the compositions of agents delaying absorption, for example, aluminum monostearate and gelatin.

[0178] Sterile injectable solutions are prepared by incorporating the active compounds in the required amount in the appropriate solvent with various of the other ingredients enumerated above, as required, followed by filtered sterilization (e.g., sterile filtration using a microfilter with a typical pore size of about 0.22 pm or less). Generally, dispersions are prepared by incorporating the various sterilized active ingredient into a sterile vehicle which contains the basic dispersion medium and the required other ingredients from those enumerated above. In the case of preparing sterile powders for the manufacture of sterile injectable solutions, the preferred methods of preparation are vacuum drying, or freeze-drying optionally together with any additional desired ingredient.

[0179] Alternative sterile preparation techniques include autoclaving or ionizing radiation sterilization (i.e., gamma-radiation sterilization) of individual ingredients and primary packaging material or the whole formulation. In case of sterilization of individual ingredients and the primary packaging material, the individual components must be handled in a way that avoids contamination, i.e. may be handled in a sterile environment to prevent contamination during handling, mixing and filling into the primary packaging material, such as the vials, bottle, or infusion bags.

[0180] It is especially advantageous to formulate parenteral compositions in unit dosage forms for ease of administration and dosage uniformity. A unit dosage form as used herein refers to physically discrete units suited for administration as unitary dosages for the mammalian subjects to be treated; each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier.

[0181] The principal active ingredients are compounded for convenient and effective administration in effective amounts with a suitable pharmaceutically acceptable carrier in a unit dosage form as hereinbefore described. A unit dosage form can, for example, be prepared using kits described herein. The dosages for some therapeutic agents described herein may be determined by reference to the usual dose and manner of administration of the said ingredients.

[0182] These pharmaceutical compositions can be manufactured using methods known in the art, e.g., by conventional mixing, dissolving, levigating, emulsifying, encapsulating, entrapping, or lyophilizing processes. Methods known in the art for making pharmaceutical compositions are found, for example, in Remington: The Science and Practice of Pharmacy, 21st Ed., Gennaro, Ed., Lippincott Williams & Wilkins (2005), and Encyclopedia of Pharmaceutical Technology, eds. J. Swarbrick and J. C. Boylan, 1988-1999, Marcel Dekker, New York. Proper formulation is dependent upon the route of administration chosen.

[0183] The dosage of the individual compounds administered as combination treatments used in the methods described herein, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof, can vary depending on many factors, e.g., the pharmacodynamic properties of the compound; the mode of administration; the age, health, and weight of the recipient; the nature and extent of the symptoms; the frequency of the treatment, and the type of concurrent treatment, if any; and the clearance rate of the compound in the individual to be treated. One of skill in the art can determine the appropriate dosage based on the above factors. The compounds used in the methods described herein may be administered initially in a suitable dosage that may be adjusted as required, depending on the clinical response. In general, a suitable daily dose of each of the compounds in combinations will be that amount of each compound that is the lowest dose effective to produce a therapeutic effect. Such an effective dose will generally depend upon the factors described above.

[0184] A compound identified as capable of treating any of the conditions described herein if administered in the combination of compounds, using any of the methods described herein, may be administered to patients or animals as a pharmaceutical composition (e.g., in unit dosage form). The chemical compounds for use in such therapies may be produced and isolated by any standard technique known to those in the field of medicinal chemistry. Conventional pharmaceutical practice may be employed to provide suitable pharmaceutical compositions to administer the identified compound to patients suffering from traumatic brain injury, brain infection, brain abscess, stroke, cardiac stroke, brain ischemia including ischemic stroke, status epilepticus, and brain tumors. The treatment is initiated after the occurrence / diagnosis of the respective insult, and aims at treating epileptogenesis, and in the case of cardiac stroke, treatment of the consequences of the stroke, to limit the size of the insult, to increase the survival rate, and to reduce the disability resulting from the cardiac stroke. Administration may begin before the patient is symptomatic. Exemplary routes of administration of the pharmaceutical compositions include oral, intranasal, intradermal, intramuscular, parenteral, intravenous, intra-arterial, intracranial, subcutaneous, intraorbital, intraventricular, intraspinal, intrathecal, and intraperitoneal.

[0185] In certain embodiments, the pharmaceutical compositions described herein include those formulated for oral administration. In some embodiments, the pharmaceutical composition is in the form of a solution or suspension. In a preferred embodiment, the pharmaceutical composition is a solution.

[0186] In some embodiments, the pharmaceutical composition includes aqueous solutions, suitably flavored syrups, aqueous or oil suspensions, and flavored emulsions with edible oils, e.g., cottonseed oil, sesame oil, coconut oil, or peanut oil, as well as elixirs and similar pharmaceutical vehicles.

[0187] Principles useful in the formulation of pharmaceutical compositions and kits therefor are described, e.g., in Remington: The Science and Practice of Pharmacy, 21st Ed., Gennaro, Ed., Lippincott Williams & Wilkins (2005) and in The United States Pharmacopeia: The National Formulary (USP 36 NF31), published in 2013.

[0188] Definitions

[0189] Unless otherwise defined herein, scientific and technical terms used in this application shall have the meanings that are commonly understood by those of ordinary skill in the art. Generally, nomenclature used in connection with, and techniques of, chemistry, cell and tissue culture, molecular biology, cell and cancer biology, neurobiology, neurochemistry, virology, immunology, microbiology, pharmacology, genetics and protein and nucleic acid chemistry, described herein, are those well known and commonly used in the art.

[0190] The methods and techniques of the present disclosure are generally performed, unless otherwise indicated, according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout this specification. See, e.g. “Principles of Neural Science”, McGraw-Hill Medical, New York, N.Y. (2000); Motulsky, “Intuitive Biostatistics”, Oxford University Press, Inc. (1995); Lodish et al., “Molecular Cell Biology, 4th ed.”, W. H. Freeman & Co., New York (2000); Griffiths et al., “Introduction to Genetic Analysis, 7th ed.”, W. H. Freeman & Co., N.Y. (1999); and Gilbert et al., “Developmental Biology, 6th ed.”, Sinauer Associates, Inc., Sunderland, MA (2000). Chemistry terms used herein, unless otherwise defined herein, are used according to conventional usage in the art, as exemplified by “The McGraw-Hill Dictionary of Chemical Terms”, Parker S., Ed., McGraw-Hill, San Francisco, C.A. (1985).

[0191] All of the above, and any other publications, patents and published patent applications referred to in this application are specifically incorporated by reference herein. In case of conflict, the present specification, including its specific definitions, will control.

[0192] The term “agent” is used herein to denote a chemical compound (such as an organic or inorganic compound, a mixture of chemical compounds), a biological macromolecule (such as a nucleic acid, an antibody, including parts thereof as well as humanized, chimeric and human antibodies and monoclonal antibodies, a protein or portion thereof, e.g., a peptide, a lipid, a carbohydrate), or an extract made from biological materials such as bacteria, plants, fungi, or animal (particularly mammalian) cells or tissues. Agents include, for example, agents whose structure is known, and those whose structure is not known.

[0193] A “patient,” “subject,” or “individual” are used interchangeably and refer to either a human or a non-human animal. These terms include mammals, such as humans, primates, livestock animals (including bovines, porcines, etc.), companion animals (e.g., canines, felines, etc.) and rodents (e.g., mice and rats).

[0194] The term “liquid pharmaceutical composition,” as used herein, refers to those pharmaceutical compositions in the form of pharmaceutical solutions and pharmaceutical suspensions. Preferably, a liquid pharmaceutical composition (e.g., a parenteral, liquid pharmaceutical composition) is a solution.

[0195] The term “pharmaceutically acceptable,” as used herein, refers to those compounds, materials, compositions, and / or dosage forms, which are suitable for contact with the tissues of an individual (e.g., a human), without excessive toxicity, irritation, allergic response and other problem complications commensurate with a reasonable benefit / risk ratio.

[0196] The phrase “pharmaceutically acceptable carrier” as used herein means a pharmaceutically acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material useful for formulating a drug for medicinal or therapeutic use.

[0197] The term “pharmaceutical composition,” as used herein, represents a composition containing one or more compounds described herein, formulated with a pharmaceutically acceptable excipient, and typically manufactured or sold with the approval of a governmental regulatory agency as part of a therapeutic regimen for the treatment of a disease in a mammal. Pharmaceutical compositions can be formulated, for example, for oral administration in unit dosage form (e.g., an oral solution-gelcap, or syrup); for topical administration (e.g., as a cream, gel, lotion, or ointment); for intravenous administration (e.g., as a sterile solution free of particulate emboli and in a solvent system suitable for intravenous use); or in any other formulation described herein.

[0198] “Pharmaceutically acceptable salt” or “salt” is used herein to refer to an acid addition salt or a basic addition salt which is suitable for or compatible with the treatment of patients.

[0199] The term “pharmaceutically acceptable acid addition salt” as used herein means any nontoxic organic or inorganic salt of any base compounds represented by Formula I. Illustrative inorganic acids which form suitable salts include hydrochloric, hydrobromic, sulfuric and phosphoric acids, as well as metal salts such as sodium monohydrogen orthophosphate and potassium hydrogen sulfate. Illustrative organic acids that form suitable salts include mono-, di-, and tricarboxylic acids such as glycolic, lactic, pyruvic, malonic, succinic, glutaric, fumaric, malic, tartaric, citric, ascorbic, maleic, benzoic, phenylacetic, cinnamic and salicylic acids, as well as sulfonic acids such as p-toluene sulfonic and methanesulfonic acids. Either the mono or di-acid salts can be formed, and such salts may exist in either a hydrated, solvated or substantially anhydrous form. In general, the acid addition salts of compounds of Formula I are more soluble in water and various hydrophilic organic solvents, and generally demonstrate higher melting points in comparison to their free base forms. The selection of the appropriate salt will be known to one skilled in the art. Other non-pharmaceutically acceptable salts, e.g., oxalates, may be used, for example, in the isolation of compounds of Formula I for laboratory use, or for subsequent conversion to a pharmaceutically acceptable acid addition salt.

[0200] The term “pharmaceutically acceptable basic addition salt” as used herein means any non-toxic organic or inorganic base addition salt of any acid compounds represented by Formula I or any of their intermediates. Illustrative inorganic bases which form suitable salts include lithium, sodium, potassium, calcium, magnesium, or barium hydroxide. Illustrative organic bases which form suitable salts include aliphatic, alicyclic, or aromatic organic amines such as methylamine, trimethylamine and picoline or ammonia. The selection of the appropriate salt will be known to a person skilled in the art. The term “polysorbate,” as used herein, refers to oleate esters of sorbitol and it’s anhydrides, typically copolymerized with ethylene oxide. In certain embodiments, the term polysorbate refers to polysorbate 80 (poly(ethylene oxide) (80) sorbitan monolaurate).

[0201] “Treating” a condition or patient refers to taking steps to obtain beneficial or desired results, including clinical results. As used herein, and as well understood in the art, “treatment” is an approach for obtaining beneficial or desired results, including clinical results. Beneficial or desired clinical results can include, but are not limited to, alleviation or amelioration of one or more symptoms or conditions, diminishment of extent of disease, stabilized (i.e. not worsening) state of disease, preventing spread of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, and remission (whether partial or total), whether detectable or undetectable. “Treatment” can also mean prolonging survival as compared to expected survival if not receiving treatment.

[0202] The term “preventing” is art-recognized, and when used in relation to a condition, such as a local recurrence (e.g., pain), a disease such as cancer, a syndrome complex such as heart failure or any other medical condition, is well understood in the art, and includes administration of a composition which reduces the frequency of, or delays the onset of, symptoms of a medical condition in a subject relative to a subject which does not receive the composition. Thus, prevention of cancer includes, for example, reducing the number of detectable cancerous growths in a population of patients receiving a prophylactic treatment relative to an untreated control population, and / or delaying the appearance of detectable cancerous growths in a treated population versus an untreated control population, e.g., by a statistically and / or clinically significant amount.

[0203] “Administering” or “administration of’ a substance, a compound or an agent to a subject can be carried out using one of a variety of methods known to those skilled in the art. For example, a compound or an agent can be administered, intravenously, arterially, intradermally, intramuscularly, intraperitoneally, subcutaneously, ocularly, sublingually, orally (by ingestion), intranasally (by inhalation), intraspinally, intracerebrally, and transdermally (by absorption, e.g., through a skin duct). A compound or agent can also appropriately be introduced by rechargeable or biodegradable polymeric devices or other devices, e.g., patches and pumps, or formulations, which provide for the extended, slow or controlled release of the compound or agent. Administering can also be performed, for example, once, a plurality of times, and / or over one or more extended periods.

[0204] Appropriate methods of administering a substance, a compound or an agent to a subject will also depend, for example, on the age and / or the physical condition of the subject and the chemical and biological properties of the compound or agent (e.g., solubility, digestibility, bioavailability, stability and toxicity). In some embodiments, a compound or an agent is administered orally, e.g., to a subject by ingestion. In some embodiments, the orally administered compound or agent is in an extended release or slow release formulation, or administered using a device for such slow or extended release.

[0205] As used herein, the phrase “conjoint administration” refers to any form of administration of two or more different therapeutic agents such that the second agent is administered while the previously administered therapeutic agent is still effective in the body (e.g., the two agents are simultaneously effective in the patient, which may include synergistic effects of the two agents). For example, the different therapeutic compounds can be administered either in the same formulation or in separate formulations, either concomitantly or sequentially. Thus, an individual who receives such treatment can benefit from a combined effect of different therapeutic agents.

[0206] A “therapeutically effective amount,” “effective amount,” “pharmaceutically effective amount,” or a “therapeutically effective dose” of a drug or agent is an amount of a drug or an agent that, when administered to a subject will have the intended therapeutic effect. The full therapeutic effect does not necessarily occur by administration of one dose, and may occur only after administration of a series of doses. Thus, a therapeutically effective amount may be administered in one or more administrations. The precise effective amount needed for a subject will depend upon, for example, the subject’s size, health and age, and the nature and extent of the condition being treated, such as cancer or MDS. The skilled worker can readily determine the effective amount for a given situation by routine experimentation.

[0207] The term “seizure disorder” as used herein refers to a seizure, a condition in which a seizure is a known symptom, or a condition that increases the risk of a seizure. In certain embodiments, the term “seizure disorder” refers to epilepsy. EXAMPLES

[0208] The invention now being generally described, it will be more readily understood by reference to the following examples, which are included merely for purposes of illustration of certain aspects and embodiments of the present invention, and are not intended to limit the invention.

[0209] Example 1 : Excipient solubility testing for a series of potential excipients and atorvastatin as ATY-Ca

[0210] Excipient compatibility is divided into a solubility and chemical stability evaluation. Prior to the initiation of the stability study, the maximum solubility of atorvastatin calcium in each excipient solution was determined. Atorvastatin calcium API was first added into each excipient vehicle listed in Table 1 below and shaken for at least 4-6 hours to induce solubilization. After 4-6 hours of shaking, solutions that were observed to be clear had additional API added followed by another round of solubilization. Additionally, for the aqueous-based samples (#1-19 in Table 1), pH was monitored throughout the study. If pH was observed to drift ± 0.1, the sample was titrated back to within specification and the sample was returned to the shaker for additional solubilization. A pH of 8.0 ± 0.1 was targeted for both the phosphate and the meglumine buffer systems as solubilization of atorvastatin calcium has been observed to shift pH. The endpoint of saturation was determined if the following was observed: (1) API particles remained visually present in the vial after 4-6 hours of shaking and (2) the pH remained within specification after 4-6 hours of shaking (as applicable).

[0211] Samples were evaluated at a starting concentration of 2 mg / mL by weighing out 4 mg of atorvastatin calcium and adding 2 mL of each respective excipient solution. For solutions where precipitate was not observed, additional atorvastatin calcium was added followed by shaking. The concentration of atorvastatin calcium was increased until all solutions were observed to have precipitate following shaking. Once saturated, samples were centrifuged for 5 minutes at 15000 RPM. The supernatant of each sample was removed from the centrifuge tube and analyzed using a validated liquid chromatography (LC) method. The atorvastatin calcium saturated solubility concentrations and pH measurements are provided in Table 2.

[0212] Based on the IV excipient solubility data, atorvastatin calcium appears to be most soluble in neat polymer polyethylene glycol 300, polyethylene glycol 400, and propylene glycol with the highest solubility observed in propylene glycol. Aside from the neat polymers, the highest solubility for atorvastatin calcium was observed in the tetrasodium EDTA chelating agent. Atorvastatin calcium also appears to have slightly higher aqueous solubility in the presence of surfactants Tween 80 and Kolliphor HS15. It was also observed that atorvastatin calcium had higher aqueous solubility in the presence of phosphate buffer species compared to meglumine buffer.

[0213] Table 1. Selection of excipients for solubility study

[0214]

[0215] Table 2. Summary of Atorvastatin Calcium Saturated Solubility for IV Delivery

[0216] 1Solubility analysis was performed assuming a correction factor of 1.00 for Atorvastatin calcium.

[0217] Example 2: Excipient chemical stability testing for a series of potential excipients and atorvastatin as ATY -Ca

[0218] Following the maximum solubility evaluation, the same excipient list was used to evaluate atorvastatin calcium chemical stability in the presence of excipients in solution. For the chemical stability experiment, a stock atorvastatin calcium solution was prepared at a concentration of 600 pg / mL in a 1 : 1 acetonitrile: water solution. The 23 excipient solutions in Table 1 were also prepared as 2X stock solutions (2X excipient amount in 100 mM buffer, pH 8 or neat organic). To make the active samples, each excipient stock solution was diluted down to viable excipient concentrations using the 600 pg / mL atorvastatin calcium 1: 1 acetonitrile: water solution to make a 300 pg / mL atorvastatin calcium 1:1:2 acetonitrile:water:excipient solution.

[0219] For all 23 atorvastatin calcium samples, corresponding placebo solutions were prepared in the same manner without the API and stored alongside the active samples throughout the study. Both active and placebo samples were pH adjusted to the target pH of 8.0 ± 0.1 and analyzed via HPEC for the T=0 timepoint. Upon completion of potency and purity analysis for the T=0 timepoint, all active and placebo samples were transferred into 10 vials of 2 mF aliquots ( 1 vial per timepoint and condition plus 1 contingency vial per condition) and placed inside 25°C / 60% RH and 40°C / 75% RH chambers for a two-week stability study. Time points include T=0, 1 week, and 2 weeks, and tests include visual appearance, pH (for aqueous samples only), and potency and purity at each time point for the active samples. The placebo samples were analyzed by HPLC alongside the samples as comparison. Any peaks observed in the placebo samples were noted as being related to the excipient. The IV excipient compatibility results can be found in Table 3, Table 4, Table 5 for pH, potency and purity, respectively. Potency analysis was performed assuming a correction factor of 1.0 for atorvastatin calcium.

[0220] During sample preparation, each sample remained a clear and colorless solution free of particulates. A few samples containing higher organic contents, such as neat organics (#20-22), appeared more viscous than other samples but remained colorless and clear. All measured pH values were adjusted to be within 8.0 ±0.1.

[0221] Some variability is seen in the individual sample potencies attributed to the initial weight- by-weight sample preparation, but most samples were within an expected range of 98 - 102%, with some slight variations. Primarily, sodium metabisulfite (#10) showed a lower % potency than most other excipients at 94.4%. Additionally, tetrasodium EDTA (#23) showed a slightly higher potency at 103.8%, however its purity remained consistent with other samples at 99.6%. With a purity value trending with the other sample purities, the higher potency suggests that the sample was prepared at a higher concentration than the other samples. Although this value returned higher than expected a drop in potency for subsequent time points can still be observed by comparing values to the T=0 measurement.

[0222] All other samples had purity values that remained consistent with the observed potencies, except for metabisulfite (#10) with purity at 95.9%. The lower potency and purity values for excipient 10 suggests a rapid degradation of atorvastatin calcium in the presence of metabisulfite sodium, and an increase in related substances.

[0223] Table 3. Excipient Stability pH Results, T=0, 1 Week and 2 Weeks

[0224] Observations from T=1 Week:

[0225] Overall, samples maintained physical and chemical stability after the first week of the study with excipients 9 and 10 being the main exceptions. During the T=1 week pull, almost all samples maintained a clear and colorless appearance, however a color change was observed in ascorbic acid (#9) and its placebo. The color gradient of ascorbic acid at the T=l-week timepoint is compared with the control sample (#14), with the samples stored at 40°C showing a more pronounced color change. No visible particulates were observed in any samples.

[0226] An overall slight downward trend in pH can be observed during the T=l-week timepoint, with the 40°C samples trending below the ±0.1 tolerance observed during sample preparation. A few outliers were ascorbic acid (#9) and metabisulfite (#10) with a pH of 5.7 and 7.5 for the 25°C samples and 5.1 and 5.1 for the 40°C samples, respectively.

[0227] In general, the observed potencies for T=l-week samples stored at 25 °C were within the expected range of 98 - 102%. Similarly, to T=0, both ascorbic acid (#9) and metabisulfite (#10) showed decrease in potency compared to other excipients (92.7% and 26.6% for the 25°C condition and 83.2% and <1% for the 40°C condition, respectively), which aligns with the observed pH decrease. Additionally, excipients containing PEG 400 seem to also have a slight downward trend in the 40°C condition with excipients 2, 13 and 19 all returning with slightly decreased potency values. This observation aligns with the decrease in potency for the neat PEG 300 and PEG 400 excipients at the elevated condition.

[0228] The overall sample purity trend in the excipient samples aligns with observed trends in potencies and pH during the T=l-week time point. Both ascorbic acid and metabisulfite had lower observed purity than other excipients, with atorvastatin being completely degraded in the sodium metabisulfite sample at the elevated temperature. Additionally, an overall slight decrease in purity can be seen trending in the 40°C condition, with samples containing PEG 300 and PEG 400 dropping below a purity of 97%.

[0229] Table 4: Excipient Stability Atorvastatin Calcium Assay Results, T=0, 1 week, and 2 weeks Table 5. Excipient Stability Atorvastatin Calcium Purity Results, T=0, 1 week, and 2 weeks

[0230] Observations from T=2 Weeks:

[0231] Precipitation was not observed in any vials throughout the entire study, a strong indication of physical stability with the selected excipients. Both the active and placebo ascorbic acid (#9) samples continued to change color and were observed to be a darker yellow solution at the end of the study. The change in solution color in both active and placebo vials suggests that the color change is not related to an interaction between ascorbic acid and atorvastatin.

[0232] A downward pH trend was continued to be observed in samples throughout the study, with excipients 9 and 10 dropping down to pH 5 at both temperature conditions by the end of the study. Additionally, samples containing PEGs continued to drop to lower pH values, with excipient 13 decreasing to a pH of 7.5 for the 25°C condition and 7.4 for the 40°C condition.

[0233] Potency values remained stable in the 25 °C condition but a downward trend was observed in the 40°C condition with potencies of 96% observed for most samples. The greatest decrease in potency was observed for both ascorbic acid (#9) and metabisulfite (#10), which showed less than 90% potency at both conditions for #9 and complete loss of potency for #10 at both conditions. Samples containing ethanol and PEGS also continued to display a downward shift in potency in the 40°C conditions.

[0234] Purity values align with observed potency decreases with a general downward trend in purity for all 40°C samples. Samples containing PEG showed a slightly larger downward trend in purity with purity values of 91.5% and 90.4% for samples 13 and 21 respectively. Additionally, sample 10 appeared to have almost completely degraded over the course of the study in both the 25 °C and 40 °C conditions.

[0235] Excipient Compatibility Conclusions

[0236] A generic UPLC analytical method was established for the quantitation of atorvastatin calcium in support of the excipient solubility study. The method was shown to be linear within 200% - 2% nominal range, and acceptable accuracy (98% - 102%) throughout the range. The method was utilized for subsequent solubility testing as stability-indicating method. The excipient compatibility for IV administration study can be executed via solubility and stability evaluation of atorvastatin calcium. The results of the solubility study demonstrate that atorvastatin calcium had highest solubility in the neat organics PEG 300, PEG 400 and PG with the latter having the highest solubility of all excipients tested. Additionally, atorvastatin calcium has the highest aqueous solubility in the presence of tetrasodium EDTA and good solubility in the presence of surfactants, specifically Tween 80 and Kolliphor HS15. Solubility was found to be higher in sodium phosphate buffered system when compared to the meglumine buffer system.

[0237] The results of the stability portion of the excipient compatibility study demonstrate that atorvastatin calcium generally has strong physical and chemical stability in most excipients over the course of two weeks. No difference in stability was observed between the phosphate buffered samples and the meglumine buffered samples. While the neat organic solvents demonstrated a higher maximum solubility than the aqueous samples, it should be noted that the samples containing higher amounts of organics (PEG 300 and PEG 400) had poor stability at the 40°C condition. Of the organic co-solvents used, propylene glycol appeared to remain the most stable throughout the study remaining in trend with most other aqueous based samples. Throughout the study, both ascorbic acid and metabisulfite performed poorly, indicating that atorvastatin calcium does not remain stable when in the presence of these excipients even after 1-week (see table 5).

[0238] Results from the excipient compatibility study demonstrate that atorvastatin calcium is both soluble and stable in multiple excipients. A few excipients that stood out in both the solubility and stability studies are propylene glycol, polysorbate 80 (tween 80), kolliphor HS15 and tetrasodium EDTA. While other organic co-solvents (ethanol, PEG 300, and PEG 400) all demonstrated good solubility, propylene glycol stands out among them as it has both higher solubility and stability with atorvastatin calcium than other co-solvents. Additionally, with no differences in stability observed, the phosphate buffer species stands out due to its higher maximum solubility when compared to the meglumine buffer system. It is also worth noting the higher maximum solubility of atorvastatin in the presence of tetrasodium EDTA (#23) however the presence of sodium in both the high performing phosphate buffer species and EDTA could suggest that the presence of sodium may have an impact on the solubility of atorvastatin calcium. Example 3: Test formulations

[0239] Following the atorvastatin calcium excipient screen, it was noted that the API showed highest solubility in the presence of propylene glycol and polysorbate 80 (see table 2 for comparative data). Experimental formulations were devised using organic co-solvents in combination with polysorbate 80. Additionally, meglumine was included due to its solubility inducing effects on atorvastatin calcium. Different combinations of tetrasodium EDTA were also included to induce solubility via ion exchange. Finally, test formulations were buffered at pH 8.0 using a phosphate buffering system Table 6 provides a summary of the formulations evaluated, their composition, and the visual observations upon compounding.

[0240] Table 6. Test Formulation Composition and Visual Observations

[0241]

[0242]

[0243] Test formulations 1A-1E and 2A-2E were prepared using an order of addition approach. Atorvastatin calcium was first weighed out into vials followed by the addition of organic cosolvents and surfactants and then a concentrated aqueous stock solution. All aqueous components were first dissolved in a phosphate buffer at pH 8.0 to create a concentrated aqueous stock solution. After addition of each component, the formulation was vortexed and sonicated.

[0244] Formulations 1A-1E all contained an atorvastatin concentration of 5 mg / mL while formulations 2A-2E contained a concentration of 2 mg / mL.

[0245] Overall, the formulations containing a concentration of 2 mg / mL presented without precipitation of remaining drug substance, while formulations containing 5 mg / mL showed evidence of incomplete dissolution. It was also noted that formulations containing more aggressive amounts of solvent and surfactant (e.g. propylene glycol, polysorbate 80) outperformed less aggressive formulations which did not contain these solvents. An aliquot of all 10 formulations were centrifuged, the supernatant was extracted and then analyzed for recovery via HPLC. The recovery of atorvastatin calcium can be seen in Table 7 below.

[0246] Table 7. Atorvastatin recovery in Formulations 1A-1E and 2A-2E

[0247] Among the 10 formulations, both formulations IE and 2E had the highest concentration relative to other formulations with the same concentration. The high concentration of atorvastatin calcium indicates that the particulates seen in formulations IE and 2E are salts that came out of solution rather than insoluble atorvastatin calcium. Formulation 2E was modified to remove the presence of salts and was re-prepared as formulations 3A-3D. All four formulations were prepared without meglumine and 3C and 3D were prepared without the presence of a phosphate buffering system. Various solvent and surfactant compositions were used.

[0248] Visual particulates were observed in formulations 3A-3D. An order of addition approach was used when preparing all 4 formulations and involved sonicating and vertexing immediately following each addition. The visual precipitation observed in these formulations suggest that the presence of floating particles in solution was not dependent on the presence of meglumine or phosphate buffer salts. Formulation_2E was then reprepared using a new process. This process involved stirring at 30°C for 1 hour to induce the ion exchange and facilitate solubilization. Formulations 4A-4C were prepared first, each with slightly different combinations of atorvastatin calcium, propylene glycol or tetrasodium EDTA. After atorvastatin calcium was weighed into the vial, propylene glycol and polysorbate 80 were added and the resulting mixture was stirred for 1 hour at 30°C. After 1 hour, a clear viscous mixture was obtained and the aqueous solution containing salts was then added into the vial. Formulations 4A and 4B achieved a clear colorless solution after mixing for 1 hour while formulation 4C remained slightly gray with some floating particulates.

[0249] Formulation 4A and 4B were then analyzed for pH, osmolality and viscosity after overnight storage. The pH, osmolality and viscosity of both samples can be seen in Table 8 and Table 9 below. Additionally, atorvastatin recovery was analyzed via HPLC and can be observed in Table 10 below. The high osmolality observed in 4A and the slight decrease in 4B suggest that the presence of propylene glycolincreased the osmolality of the formulation. The same compounding process was used in formulations 4D and 4E replacing propylene glycol with polyethylene glycol 400 to try and decrease the osmolality. Upon completion of compounding, both formulations were clear and colorless with some floating particles present in the solution.

[0250] Table 8. pH, Osmolality and Viscosity of Formulation 4A

[0251] Table 9. Atorvastatin Recovery of Formulation 4A in various conditions

[0252] Table 10. pH, Osmolality and Viscosity of Formulation 4B

[0253] It was observed that formulations prepared at the 2 mg / mL scale performed much better than formulations prepared at a 5 mg / mL scale. The limit of solubility of atorvastatin calcium was then explored in the current lead test formulation, formulation 4B. The amount of tetrasodium EDTA in the aqueous portion was increased to provide excess sodium and EDTA to facilitate an ion exchange for any additional atorvastatin calcium added. After adding both the organic and aqueous components of formulation 4B, a clear colorless solution was observed. While stirring the solution and at a constant temperature of 30°C, atorvastatin calcium was then added to increase the overall formulation concentration to 2.5 mg / mL. Upon addition of atorvastatin calcium, visible floating particulates could be observed in solution. The resulting mixture was stirred for an additional hour to try and induce solubility. After 1 hour, the solution remained a colorless solution with floating particles.

[0254] Formulation 5A indicates that atorvastatin has a maximum solubility in the lead formulation of 2 mg / mL. The formulation compounding process may allow for a higher concentration of atorvastatin calcium prior to adding both the organic and aqueous components but an increase in atorvastatin concentration after both components have been added resulted in visible particulates present in solution.

[0255] Formulations 6A-6G were then prepared to explore the polysorbate 80 had with the solubility of atorvastatin calcium in solution. Among the elimination of polysorbate 80, some formulations contained different concentrations of PEG 400, PG and tetrasodium EDTA that have not been tried yet.

[0256] All 7 formulations were prepared using the compounding process used for formulation 4B.

[0257] Formulations 6A and 6C-6F all appeared colorless and clear with a small number of particles floating in solution. Formulations 6B and 6G appeared as grayish clear solutions with floating particles. The presence of particles in solution suggests that the presence of both a surfactant and solvent may be necessary for full solubilization of atorvastatin calcium.

[0258] To reduce the osmolality of the lead formulation, formulations 7A-7D were designed to explore how combinations of propylene glycol, polysorbate 80 and polyethylene glycol 400 could be changed to provide a lower osmolality while maintaining a clear colorless solution. The same compounding approach used for formulation 4B was used.

[0259] All four formulations were clear and colorless following the completion of compounding. The four formulations were then analyzed for atorvastatin recovery, osmolality, and viscosity and can be seen in Table 11 below.

[0260] The least aggressive, formulation 7 A, also had the lowest osmolality and viscosity of the four tested. All samples had potencies that were consistent with the concentration of the formulations.

[0261] Formulation 7 A was able to solubilize a 2 mg / mL concentration of atorvastatin calcium with only 5% propylene glycol present in solution. Formulation 7B was also able to solubilize a 2 mg / mL concentration of atorvastatin calcium with 10% propylene glycol but only a 0.5% polysorbate 80 concentration. These two formulations suggest that a better compounding process may allow for decreased concentrations of organics and surfactants in the final formulatiom

[0262] Table 11. Osmolality, Viscosity and Recovery for Formulations 7A-7D

[0263] Example 4: Further test formulations with reduced osmolarity

[0264] To further reduce the osmolality of the lead formulation 7A, four formulations were prepared using the optimized compounding process previously described. A lower salt concentration was explored by reducing the phosphate buffer from a 50 mM concentration to a 10 mM concentration. Formulation 7C eliminated the presence of phosphate altogether. Formulation 7D replaced tetrasodium EDTA with disodium EDTA to further reduce sodium concentration while maintaining atorvastatin calcium solubilization. The composition of the formulations can be seen in Table 12 below. The pH, potency and osmolality of the formulations can also be seen in Table 13 below.

[0265] All four formulations of the “8” series were clear and colorless upon completion of compounding. Little variation was observed in the osmolality and pH remained stable throughout the process. All four formulations had potency values that were consistent with the concentration of the samples. The reduction of polysorbate 80 from 1% to 0.5% in formulation 8A should be noted and explored in further formulations. It should be noted that formulation 8C, which was prepared without the phosphate buffer, had the lowest osmolality of the formulations prepared. This suggests that eliminating phosphate altogether may have a modest impact on osmolality of the formulations tested.

[0266] Formulation 8B was modified to explore a reduced propylene glycol concentration of 3%. The composition of this modified formulation can be seen in Table 12 below. Formulation 9 A was prepared using the following compounding process: After atorvastatin calcium was weighed into the vial, propylene glycol and polysorbate 80 were added and the resulting mixture was stirred for 1 hour at 30°C. After 1 hour, a clear viscous mixture was obtained and the aqueous solution containing salts was then added into the vial and again stirred at 30°C for one hour to obtain a clear solution. The pH, potency and osmolality of the formulation can also be seen in Table 13 below.

[0267] Table 12. Formulation Composition of Formulations 8A-8D Table 13. pH, Potency and Osmolality of Formulations 8A-8D

[0268] Formulation 9A was clear and colorless upon completion of compounding. The potency was consistent with the concentration of the sample. It should be noted that formulation 9A has the lowest osmolality of any formulation prepared.

[0269] Formulation 8A-8D and 9A were all clear and colorless upon completion of compounding. Formulation potencies were all consistent with the concentration prepared for the samples. Most notable, these five formulations all had reduced osmolality values, most likely due to a reduced buffering salt concentration. Substituting tetrasodium EDTA with disodium EDTA in formulation 8D did not appear to have an impact on formulation potency or osmolality. Formulation 8A also had similar potency and osmolality values as the other formulations suggesting that future formulations could have reduced polysorbate 80 concentrations. The largest impact on osmolality was the reduction of propylene glycol from 5% to 3% as observed in formulation 9A. The PG concentration could be further reduced to 2%.

[0270] Example 5 : Chemical stability of atorvastatin formulations

[0271] Stability of atorvastatin formulation 8B (see example 4)

[0272] In a first stability study, involving accelerated stability, atorvastatin Calcium was dissolved in formulation 8B as described in example 4.

[0273] Table 14. stability of formulation 8B

[0274]

[0275] The data indicate that there was no decline if stored at 4°C for up to 1 month at 4°C. The decline in concentration was not present until 2 weeks of storage at both, room temperature and 50°C. Only following storage at 50°C for 1 month, there was a clear decline in atorvastatin concentration. These data demonstrate that formulation 8A is stable at room temperature for at least one month. A temperature excursion into 50°C did not lead to any degradation even for two weeks.

[0276] The lead formulation candidate 9A was modified to explore the relationship polysorbate 80 had on solution stability. The compositions of these three formulations 10 A- 10C can be seen in Table 15 below.

[0277] Table 15. Formulation Composition of Formulations 10 A- 10C

[0278]

[0279] Formulation 10A was clear and colorless upon completion of compounding. There were no visible particulates observed after initial solubilization. The osmolality of formulation 10A was recorded following completion of compounding and was observed to be 503 Osmol / kg. Formulation 10B and 10C both had visible particulates floating in the solution throughout the compounding process. Formulation 10B also appeared a hazy gray solution while formulation 10C was a slightly hazy solution.

[0280] Formulations 10 A- 10C were then left at ambient conditions for 7 days to observe the stability of the formulations. An aliquot of formulation 10A was filtered using a 0.22pm PVDF filter and was also left at ambient conditions to observe filtrated solution stability. After 7 days at ambient conditions, formulations 10B and 10C were observed to contain a gelatinous gray precipitation while formulation 10A, both filtered and nonfiltered, remained clear and colorless after 7 days at ambient conditions.

[0281] It should be noted that the osmolality of formulation 10A is close to the osmolality of formulation 9A, indicating that a reduction of polysorbate 80 from 1% to 0.5% has little effect on osmolality. Formulation 10B and 10C both were unable to initially solubilize Atorvastatin and displayed physical instability over the course of 7 days at ambient conditions. This suggests that the presence of polysorbate 80 has a large impact on the initial solubilization of Atorvastatin Calcium and could have an impact on short term stability of the solution. While formulation 10A does provide the least content of organic solvents, the lower concentration of excipients may impact long term stability. After 15 days, both the filtered and unfiltered formulation 10A remained clear and free of visible particulates. The unfiltered formulation 10A was analyzed via HPLC for potency and purity. The potency and purity of formulation 10A was as follows: potency 101.40%, purity 98.12%. The osmolality of formulation 10A was measured to be 503 mOsmol / kg. Formulation 10A had a potency that was consistent with the expected theoretical value. Impurities above 0.05% were present in the 15-day sample that were not observed in the main standard or diluent blank, which might indicate some chemical instability.

[0282] A two months stability study was conducted with both, formulation 9A an formulation 10A. Two storage conditions, i.e. 5°C + / - 3°C with ambient relative humidity, and 25°C + / - 2°C and 60° relative humidity + / - 5% relative humidity. Solutions were stored in glass vials with screw cap.

[0283] Both formulations were found to be stable for 1 month at both temperature conditions with purity and pH to remain stable. The purity value remained above 99% for both storage conditions. After two months storage at 25 °C and 60% relative humidity, the purity value started to be reduced at the 25 °C storage condition for formulation 10 A, but not for formulation 9 A. At 5°C, both formulations remained stable over 2 months. These data indicate, that polysorbate 80 at 1 % helps to stabilize chemically an atorvastatin solution.

[0284] The stability study of formulation 9A was repeated under conditions of absence of oxygen. After complete manufacturing of the atorvastatin solution, the solution was bubbled for 2 min with pure nitrogen gas to remove oxygen from the solution and from the space above the solution. The vials were immediately thereafter closed with silicon stoppers and aluminum crimp caps, to ensure airtight closure. Two storage conditions, i.e. 5°C + / - 3°C with ambient relative humidity, and 25°C + / - 2°C and 60° relative humidity + / - 5% relative humidity, were applied with 4 weeks and 8 weeks of storage. Under this condition, i.e. removal of oxygen both, from the solution and from the space above the solution in the vial, the solution remained fully stable at both storage conditions with no indication of chemical degradation even at 25 °C for 4 and 8 weeks of storage.

[0285] In a separate stability study, atorvastatin was dissolved in either demineralized water for injection at the solubility limit of 0.6 mg / ml, or in a solution of 0.3% meglumine in demineralized water and stored at room temperature (25°C + / -2°C) or refrigerated (5°C + / - 3°C) for 3 months. In this experiment, the atorvastatin content and purity started to decline at the 3 months time point at room temperature to about 94% and at refrigerated temperatures to about 96% while the purity in the meglumine solution remained to be at 98% at refrigerated temperature, while it started to decline to 97% at room temperature. These data indicate, that meglumine also contributes to the chemical stability of atorvastatin solution.

[0286] Example 6: Combination product

[0287] Taking formulation 9 A at 2 mg / ml, a combination solution was manufactured. 10 ml of formulation 9A were taken, containing 20 mg atorvastatin, and 300 mg levetiracetam was added to the 10 ml solution. Within 5 min of slowly stirring the solution, levetiracetam was completely dissolved. In further tests, the levetiracetam concentration was varied to 20 mg / ml, 60 mg / ml, and 100 mg / ml in all cases, levetiracetam could be easily dissolved without causing precipitation of any kind by stirring for 5 min.

[0288] As next step, 20 mg / ml, 30 mg / ml, 60 mg / ml or 100 mg / ml ceftriaxone was added to each of the combination formulations containing 2 mg / ml atorvastatin and 20 mg / ml, 30 mg / ml, 60 mg / ml, or 100 mg / ml levetiracetam. By means of careful stirring, a complete dissolution of ceftriaxone was be achieved for all these triple combinations.

[0289] As a further iteration, formulation 9A was used and seletracetam was added at 2 mg / ml, 4 mg / ml and 10 mg / ml, followed by addition of ceftriaxone 20 mg / ml, 30 mg / ml, 60 mg / ml or 100 mg / ml to form triple combinations containing atorvastatin 2 mg / ml, seletracetam 2-10 mg / ml, and ceftriaxone, 30-100 mg / ml. All triple combinations could be formulated and complete dissolution was obtained, without any visible remaining crystals.

[0290] Upon storage of all of the prepared triple combination solutions at room temperature (20°C-25°C) or refrigerated (2°C to 8°C) for 24 h and for 28 days, no precipitation was observed and a completely clear solution remained to be present, indicating physical stability of the triple combinations which are based on formulation 9A.

[0291] Example 7: Safety of formulation 9 A

[0292] To evaluate the local tolerance and systemic safety of formulation 9A, this formulation was tested in a 5 day repeat-dose toxicity study in Wistar rats. The formulation 9 A was intravenously administered to groups of 10 male and 10 female Wistar rats at a dosing volume of 5 ml / kg, i.e. a dose of 10 mg / kg was administered daily as intravenous bolus administration, daily for 5 consecutive days. A 2ndgroup of rats was treated with the vehicle only. Additional 5 male and 5 female rats per group served as recovery group animals, and additional animals were included to serve as toxicokinetic satellite groups, to evaluate plasma exposure. On the 6thday, the main group animals were sacrificed and underwent full pathology and histopathology examination. In addition, hematology, clinical chemistry, and urine analysis was performed, and organ weights were recorded. The recovery animals were sacrificed after 14 days of recovery and underwent the same evaluations. The administration of atorvastatin using this formulation was well tolerated. No signs of local irritation at the injection site or of blood incompatibility were noted. In addition, no signs of local or systemic toxicity could be observed. It can be concluded atorvastatin, if administered intravenously as bolus administration, is well tolerated, even at the high dose of 10 mg / kg in Wistar rats.

[0293] INCORPORATION BY REFERENCE

[0294] All publications and patents mentioned herein are hereby incorporated by reference in their entirety as if each individual publication or patent was specifically and individually indicated to be incorporated by reference. In case of conflict, the present application, including any definitions herein, will control.

[0295] EQUIVALENTS

[0296] While specific embodiments of the subject invention have been discussed, the above specification is illustrative and not restrictive. Many variations of the invention will become apparent to those skilled in the art upon review of this specification and the claims below. The full scope of the invention should be determined by reference to the claims, along with their full scope of equivalents, and the specification, along with such variations.

Claims

We claim:

1. A pharmaceutical composition comprising atorvastatin, or a salt thereof, and a liquid carrier; wherein the liquid carrier comprises ethylenediaminetetraacetic acid (EDTA), or a salt thereof.

2. The composition of claim 1 , wherein at least a portion of the atorvastatin, or salt thereof, is dissolved within the liquid carrier.

3. A pharmaceutical composition comprising atorvastatin, or a salt thereof, and a liquid carrier; wherein the atorvastatin, or salt thereof, is dissolved within the liquid carrier at a concentration of at least 0.7 mg / mL.

4. The composition of claim 3, wherein the liquid carrier comprises a chelating agent.

5. The composition of claim 3 or claim 4, wherein the chelating agent is selected from dimercaprol, penicillamine, trientine, deferasirox, deferiprone, deferoxasurrmine, EDTA, or succimer, or a salt of any of the foregoing, or any combination thereof.

6. The composition of claim 5, wherein the chelating agent is EDTA, or a salt thereof.

7. The composition of any one of claims 1-6, wherein the atorvastatin, or salt thereof, is dissolved within the liquid carrier at a concentration of 0.7 mg / mL to 3.0 mg / mL.

8. The composition of claim 7, wherein the atorvastatin, or salt thereof, is dissolved within the liquid carrier at a concentration of 1.0 mg / mL to 2.5 mg / mL.

9. The composition of claim 8, wherein the atorvastatin, or salt thereof, is dissolved within the liquid carrier at a concentration of about 2 mg / mL atorvastatin.

10. The composition of any one of claims 1-9, wherein the liquid carrier comprises 0.01% to 0.20% (w / w) EDTA, or a salt thereof.

11. The composition of claim 10, wherein the liquid carrier comprises 0.05% to 0.10% (w / w) EDTA, or a salt thereof.

12. The composition of claim 11, wherein the liquid carrier comprises about 0.07% (w / w) EDTA, or a salt thereof.

13. The composition of any one of claims 1-2 and 6-12, wherein the EDTA or salt thereof is disodium EDTA or tetrasodium EDTA.

14. The composition of any one of claims 1-13, wherein the atorvastatin or salt thereof is atorvastatin calcium.

15. The composition of any one of claims 1-14, wherein the liquid carrier comprises at least 70% (w / w) water.

16. The composition of claim 15, wherein the liquid carrier comprises at least 90% (w / w) water.

17. The composition of claim 16, wherein the liquid carrier comprises 92% to 97% (w / w) water.

18. The composition of any one of claims 1-17, wherein the liquid carrier comprises meglumine.

19. The composition of claim 18, wherein the liquid carrier comprises 0.1% to 0.5% (w / w) meglumine.

20. The composition of any one of claims 1-19, wherein the liquid carrier comprises a surfactant.

21. The composition of claim 20, wherein the surfactant comprises polysorbate 80, polysorbate 20, a polyethylene glycol ester, a polyethylene glycol, a glycerol ether, a glyceryl monoleate, or lecithin.

22. The composition of claim 21, wherein the surfactant comprises polysorbate 80.

23. The composition of any one of claims 20-22, wherein the liquid carrier comprises about 1 % (w / w) polysorbate 80.

24. The composition of any one of claims 1-23, wherein the liquid carrier does not comprise an antioxidant.

25. The composition of any one of claims 1-24, wherein the liquid carrier comprises propylene glycol.

26. The composition of claim 25, wherein the liquid carrier comprises 1% to 10% (w / w) propylene glycol.

27. The composition of any one of claims 1-26, wherein the liquid carrier comprises a buffering agent.

28. The composition of claim 27, wherein the buffering agent is selected from acetic acid, citric acid, sodium citrate, sodium carbonate, sodium tetraborate, sodium phosphate, sodium acetate, meglumine, meglumine hydrochloride, sodium bicarbonate, or potassium phosphate, or a combination thereof.

29. The composition of claim 28, wherein the buffering agent is sodium phosphate or potassium phosphate.

30. The composition of any one of claims 1-29, wherein the composition has a pH of 6-10.

31. The composition of claim 30, wherein the composition has a pH of about 8.

32. The composition of any one of claims 1-31, wherein the osmolality of the composition is 200 to 3,000 Osmol / kg.

33. The composition of claim 32, wherein the osmolality of the composition is 300 to 700 Osmol / kg.

34. The composition of claim 33, wherein the osmolality of the composition is about 500 Osmol / kg.

35. A pharmaceutical composition comprising atorvastatin calcium and a liquid carrier; wherein the atorvastatin calcium is dissolved within the liquid carrier at a concentration of about 2 mg / mL; and wherein the liquid carrier comprises: about 0.3% (w / w) meglumine or a salt thereof; about 3% (w / w) propylene glycol; about 1% (w / w) polysorbate 80; about 0.07% (w / w) tetrasodium EDTA; and93% to 97% (w / w) 10 millimolar phosphate in water.

36. The composition of any one of claims 1-35, further comprising one or more additional therapeutic agents.

37. The composition of claim 36, wherein the one or more additional therapeutic agents is selected from levetiracetam, seletracetam, and brivaracetam, or a combination thereof.

38. The composition of claim 37, wherein the one or more additional therapeutic agents is seletracetam.

39. The composition of claim 37, wherein the one or more additional therapeutic agents is levetiracetam.

40. The composition of claim 36, wherein the one or more additional therapeutic agents is selected from ceftriaxone, or a salt thereof, and clavulanic acid, or a salt thereof, or a combination thereof.

41. The composition of claim 36, wherein the one or more additional therapeutic agents is a combination of: an SV2A agonist selected from the group consisting of levetiracetam, seletracetam, and brivaracetam, or a combination thereof; and an antibiotic selected from the group consisting of ceftriaxone, or a salt thereof, and clavulanic acid, or a salt thereof, or a combination thereof.

42. The composition of claim 41, wherein the SV2A agonist is levetiracetam and the antibiotic is ceftriaxone, or a salt thereof.

43. The composition of claim 41, wherein the SV2A agonist is seletracetam and the antibiotic is ceftriaxone, or a salt thereof.

44. A method of administering atorvastatin to a subject comprising administering a pharmaceutical composition comprising atorvastatin, or a salt thereof, to the subject parentally.

45. A method of administering a combination of atorvastatin, or a salt thereof, an SV2A agonist, and an antibiotic to a subject comprising parenterally administering to the subject a pharmaceutical composition comprising atorvastatin, or a salt thereof, an SV2A agonist, and an antibiotic.

46. The method of claim 45, wherein the SV2A agonist is selected from the group consisting of levetiracetam, seletracetam, and brivaracetam, or a combination thereof.

47. The method of claim 45 or 46, wherein the antibiotic is selected from the group consisting of ceftriaxone, or a salt thereof, and clavulanic acid, or a salt thereof, or a combination thereof.

48. The method of any one of claims 45-47, wherein the SV2A agonist is levetiracetam and the antibiotic is ceftriaxone, or a salt thereof.

49. The method of any one of claims 45-47, wherein the SV2A agonist is seletracetam and the antibiotic is ceftriaxone, or a salt thereof.

50. The method of any one of claims 44-49, wherein the composition is administered intravenously.

51. The method of any one of claims 44-49, wherein the composition is administered subcutaneously.

52. The method of any one of claims 44-49, wherein the atorvastatin, or salt thereof, is administered intramuscularly.

53. The method of any one of claims 44-49, wherein the composition is administered intradermally, intrathecally, or intraperitoneally.

54. The method of any one of any one of claims 44-49, comprising administering to the subject the composition of any one of claims 1-43.

55. A method of administering atorvastatin to a subject comprising orally administering to the subject the composition of any one of claims 1-43.

56. The method of any one of claims 44-55, wherein the subject suffers from dysphagia.

57. The method of any one of claims 44-56, wherein the subject is in a state of reduced consciousness.

58. The method of any one of claims 44-57, wherein the subject suffers from a gastric disorder.

59. A method of treating a seizure disorder in a subject in need thereof comprising administering to the subject the composition of any one of claims 1-43.

60. The method of claim 59, wherein the seizure disorder is epilepsy.

61. A method of treating dyslipidemia in a subject in need thereof comprising administering to the subject the composition of any one of claims 1-43.

62. The method of claim 61, wherein the subject has experienced a heart attack or a stroke.

63. A method of treating an infection in a subject in need thereof, comprising administering to the subject the composition of any one of claims 1-43.

64. A method of treating epileptogenesis in a subject in need thereof, comprising administering to the subject the pharmaceutical composition of any one of claims 1-43.

65. The method of claim 64, wherein the subject has experienced a traumatic brain injury.

66. The method of claim 64 or 65, comprising administering the composition of any one of claims 37 - 43.

67. A kit comprising a first container and a second container, wherein: the first container comprises atorvastatin, or a pharmaceutically acceptable salt thereof, and EDTA, or a pharmaceutically acceptable salt thereof; and the second container comprises a pharmaceutically acceptable solution comprising water and propylene glycol.

68. The kit of claim 67, wherein the first container further comprises levetiracetam, seletracetam, or brivaracetam.

69. The kit of claim 67 or claim 68, wherein the first container further comprises ceftriaxone, or a salt thereof, or clavulanic acid, or a salt thereof.

70. The kit of any one of claims 67-69, wherein the second container further comprises meglumine or a salt thereof, polysorbate 80, and a buffering agent.

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