EA045280B1 - PHARMACEUTICAL COMPOSITION - Google Patents

Description

Link to related applications

This invention claims priority to U.S. Provisional Application No. 62/423,124, filed Nov. 16, 2016, and U.S. Provisional Application No. 62/545,857, filed Aug. 15, 2017, which are incorporated herein in their entirety. via link.

BACKGROUND OF THE INVENTION

Monoacylglycerol lipase (MAGL) is an enzyme responsible for the hydrolysis of endocannabinoids such as 2-AG (2-arachidonoylglycerol), an arachidonate-based lipid, in the nervous system. 1,1,1,3,3,3-G exafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1 carboxylate is a MAGL inhibitor.

Brief Disclosure of the Present Invention

Provided herein are pharmaceutical compositions in solid dosage form containing 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof. In one aspect, described herein is a pharmaceutical composition in solid dosage form comprising:

(a) about 1 to about 60 mg 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl)benzyl)piperazine-1 -carboxylate or a pharmaceutically acceptable salt thereof;

(b) from about 5 to about 425 mg of polymer carrier;

(c) from about 0.2 to about 10 mg of surfactant; and (d) 0.2 to 10 mg of glidant.

In some embodiments, the pharmaceutical composition contains from about 10 to about 150 mg of polymeric carrier. In some embodiments, the pharmaceutical composition contains from about 14 to about 85 mg of polymeric carrier. In some embodiments, the polymeric carrier is selected from polyvinylpyrrolidone K30 (PVP K30), polyvinylpyrrolidone K17 (PVP K17), polyvinylpyrrolidone K12 (PVP K12), polyvinylpyrrolidone/vinyl acetate (PVPVA 64), hydroxypropyl methylcellulose (HPMC), hydroxypropyl methylcellulose acetyl succinate (HPMC AS), and methyl methacrylate polymers (Eudragit polymers). In some embodiments, the polymeric carrier is polyvinylpyrrolidone K30 (PVP K30). In some embodiments, the polymeric carrier is polyvinylpyrrolidone/vinyl acetate (PVPVA 64).

In some embodiments, the pharmaceutical composition contains from about 0.2 to about 4 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 2 mg of surfactant. In some embodiments, the surfactant is selected from polysorbates, polaxomers, bile salts, glyceryl monostearate, sodium lauryl sulfate, sorbitan monooleate, polyoxyethylene sorbitan monooleate, ethylene oxide-propylene oxide copolymers, and d-a-tocopheryl polyethylene glycol succinate (Vitamin E TPGS). In some embodiments, the surfactant is polysorbate 80 (Tween 80).

In some embodiments, the pharmaceutical composition contains from about 0.2 to about 4 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 2 mg of glidant. In some embodiments, the glidant is silica or talc. In some embodiments, the glidant is silica.

In some embodiments, the pharmaceutical composition further comprises a buffer selected from potassium dihydrogen phosphate, sodium bicarbonate, magnesium carbonate, sodium citrate, sodium dihydrogen phosphate, dipotassium monohydrogen phosphate, and disodium monohydrogen phosphate.

In some embodiments, the pharmaceutical composition contains from about 0.1 to about 5 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 2 mg of potassium dihydrogen phosphate.

In some embodiments, the pharmaceutical composition further contains from about 1 to about 65 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains from about 1 to about 30 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains from about 2 to about 15 mg of plasticizer. In some embodiments, the plasticizer is selected from PEG-400, triethyl citrate, triacetin, acetyl tributyl citrate, acetyl triethyl citrate, stearic acid, glycerin, polyethylene glycols, polyethylene glycol monomethyl ether, propylene glycol, sorbitan sorbitol solution, castor oil, diacetylated monoglycerides, dibutyl seb cinate and diethyl phthalate. In some embodiments, the plasticizer is PEG-400.

In some embodiments, the pharmaceutical composition further contains from about 15 to about 850 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 20 to about 400 mg of excipient. According to some

- 1045280 embodiments, the pharmaceutical composition additionally contains from about 30 to about 200 mg of excipient. In some embodiments, the filler is selected from lactose, mannitol, dicalcium phosphate, microcrystalline cellulose, siliconized microcrystalline cellulose, starch, and pregelatinized starch (1500 starch). In some embodiments, the filler is lactose, mannitol, or microcrystalline cellulose. In some embodiments, the filler is microcrystalline cellulose.

In some embodiments, the pharmaceutical composition further contains from about 3 to about 150 mg of a disintegrant. In some embodiments, the pharmaceutical composition further contains from about 5 to about 50 mg of a disintegrant. In some embodiments, the pharmaceutical composition further contains from about 6 to about 30 mg of a disintegrant. In some embodiments, the disintegrant is selected from povidone, crospovidone, hypromellose, croscarmellose sodium, hydroxypropylcellulose, and polyvinyl alcohol. In some embodiments, the disintegrant is crospovidone. In some embodiments, the leavening agent is croscarmellose sodium.

In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 10 mg of lubricant. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 4 mg of lubricant. In some embodiments, the pharmaceutical composition further contains from about 0.3 to about 1.5 mg of lubricant. In some embodiments, the lubricant is selected from magnesium stearate, stearic acid, and sodium stearyl fumarate. In some embodiments, the lubricant is sodium stearyl fumarate. In some embodiments, the lubricant is magnesium stearate.

In some embodiments, described herein is a pharmaceutical composition in solid dosage form comprising:

(a) about 1 to about 60 mg 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl)benzyl)piperazine-1 -carboxylate or a pharmaceutically acceptable salt thereof;

(b) from about 50 to about 175 mg microcrystalline cellulose;

(c) about 6 to about 15 mg croscarmellose sodium; and (d) from about 0.5 to about 2.5 mg of magnesium stearate.

In some embodiments, the pharmaceutical composition further contains from about 30 to about 200 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 50 to about 175 mg of excipient. In some embodiments, the filler is selected from lactose, mannitol, dicalcium phosphate, microcrystalline cellulose, siliconized microcrystalline cellulose, starch, and pregelatinized starch (1500 starch). In some embodiments, the filler is lactose, mannitol, or microcrystalline cellulose. In some embodiments, the filler is microcrystalline cellulose.

In some embodiments, the pharmaceutical composition further contains from about 5 to about 50 mg of a disintegrant. In some embodiments, the pharmaceutical composition further contains from about 5 to about 25 mg of a disintegrant. In some embodiments, the pharmaceutical composition further contains from about 6 to about 15 mg of a disintegrant. In some embodiments, the disintegrant is selected from povidone, crospovidone, hypromellose, croscarmellose sodium, hydroxypropylcellulose, and polyvinyl alcohol. In some embodiments, the disintegrant is crospovidone. In some embodiments, the leavening agent is croscarmellose sodium.

In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 4 mg of lubricant. In some embodiments, the pharmaceutical composition further contains from about 0.5 to about 2.5 mg of lubricant. In some embodiments, the lubricant is selected from magnesium stearate, stearic acid, and sodium stearyl fumarate. In some embodiments, the lubricant is sodium stearyl fumarate. In some embodiments, the lubricant is magnesium stearate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 30 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition contains from about 2 to about 15 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof.

In some embodiments, 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate is the free base.

- 2 045280

In some embodiments, 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate is a hydrochloride.

In some embodiments, 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate is a fumarate.

Additionally provided herein is a pharmaceutical composition in solid dosage form containing:

(a) about 2.1 mg 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl)benzyl)piperazine-1-hydrochloride carboxylate;

(b) about 156 mg microcrystalline cellulose;

(c) about 10 mg croscarmellose sodium; and (d) about 1.7 mg magnesium stearate.

Additionally provided herein is a pharmaceutical composition in solid dosage form containing:

(a) about 10.7 mg 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl)benzyl)piperazine-1-hydrochloride carboxylate;

(b) about 147 mg microcrystalline cellulose;

(c) about 10.2 mg croscarmellose sodium; and (d) about 1.7 mg magnesium stearate.

Additionally provided herein is a pharmaceutical composition in solid dosage form containing:

(a) about 53.6 mg 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl)benzyl)piperazine-1-hydrochloride carboxylate;

(b) about 104 mg microcrystalline cellulose;

(c) about 10 mg croscarmellose sodium; and (d) about 1.7 mg magnesium stearate.

Further provided herein is a pharmaceutical composition in solid dosage form, wherein the solid dosage form is a tablet.

Further provided herein is a pharmaceutical composition in solid dosage form, wherein the solid dosage form is a capsule.

In some embodiments, the solid dosage form is selected from a powder, a bite-disintegrating tablet, a chewable tablet, a capsular tablet, a capsule, a gelatin capsule, an effervescent powder, a rapid disintegrating tablet, an abuse-resistant tablet, a modified-release tablet, a modified-release capsule, modified release capsules and a powder-derived aqueous suspension. In some embodiments, the solid dosage form is a tablet. In some embodiments, the pharmaceutical composition further comprises from about 2 to about 10 mg of film coating. In some embodiments, the pharmaceutical composition further comprises from about 4 to about 8 mg of film coating. In some embodiments, the pharmaceutical composition further comprises about 2 mg of film coating. In some embodiments, the pharmaceutical composition further comprises about 3 mg of film coating. In some embodiments, the pharmaceutical composition further comprises about 4 mg of film coating. In some embodiments, the pharmaceutical composition further comprises about 5 mg of film coating. In some embodiments, the pharmaceutical composition further comprises about 6 mg of film coating. In some embodiments, the pharmaceutical composition further comprises about 7 mg of film coating. In some embodiments, the pharmaceutical composition further comprises about 8 mg of film coating. In some embodiments, the pharmaceutical composition further comprises about 9 mg of film coating. In some embodiments, the pharmaceutical composition further comprises about 10 mg of film coating. In some embodiments, the film coating is Opadry AMB II beige. In some embodiments, the solid dosage form is a capsule-shaped tablet. In some embodiments, the solid dosage form is a capsule. In some embodiments, 1,1,1,3,3,3-hexafluoropropan-2yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate, or a pharmaceutically acceptable salt thereof is crystalline. In some embodiments, 1,1,1,3,3,3hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate, or a pharmaceutically acceptable salt thereof is amorphous. In some embodiments, the pharmaceutical composition is manufactured by a hot melt extrusion process. In some embodiments, the pharmaceutical composition is manufactured by a spray drying (SDD) process. In some embodiments, the pharmaceutical composition comprises a self-emulsifying drug delivery system, a self-microemulsifying drug delivery system, or a self-nanoemulsifying drug delivery system.

Detailed Description of the Present Invention

Certain terminology.

Singular forms include references to the plural unless the context clearly requires otherwise. Thus, for example, a reference to a drug includes a reference to one or more such drugs, and a reference to an excipient includes a reference to one or more such excipients. When ranges are used herein, all combinations and subcombinations of ranges and specific embodiments therein are intended to be included. The term approximately, when applied to a number or numerical range, means that the stated number or numerical range is approximate within the limits of experimental variability (or within the statistical uncertainty of the experiment), and thus the number or numerical range varies from 1 to 15% of the stated number or numeric range.

As used herein, the terms composition and composition are used interchangeably and refer to a mixture of two or more compounds, elements or molecules. In some aspects, the terms formulation and composition can be used to refer to a mixture of one or more active agents with a carrier or other excipients.

The terms active agent, active pharmaceutical agent, drug, active ingredient, and variations thereof are used interchangeably to refer to an agent or substance that has a measurable specified or selected physiological activity when administered to a subject in a significant or effective amount.

The compound described herein is 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable compound thereof the salt is a MAGL inhibitor compound. The term 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof refers to connection with the following structure:

or a pharmaceutically acceptable salt thereof.

In some embodiments, 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate, or a pharmaceutically acceptable salt thereof is crystalline. In some embodiments, 1,1,1,3,3,3-hexafluoropropan-2yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate, or a pharmaceutically acceptable salt thereof is amorphous.

The term pharmaceutically acceptable salt refers to 1,1,1,3,3,3-hexafluoropropan-2-yl-4(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate salt, which does not cause significant irritation to the mammal to which it is administered and does not substantially abolish the biological activity and properties of the compound. A wide range of pharmaceutically acceptable salts are formed from 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1 carboxylate and includes:

acid addition salts formed by the reaction of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate with an organic acid, which includes aliphatic mono- and dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxylalkanoic acids, alkanedioic acids, aromatic acids, aliphatic and aromatic sulfonic acids, amino acids, etc. and includes, for example, acetic acid, trifluoroacetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, salicylic acid and the like;

acid addition salts formed by the reaction of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate with an inorganic acid, which includes hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, hydroiodic acid, hydrofluoric acid, phosphoric acid and the like.

In certain embodiments of the pharmaceutical formulations described herein, 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- The 1-carboxylate is in the free base form.

In certain embodiments of the pharmaceutical formulations described herein, 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate is a salt.

In certain embodiments of the pharmaceutical formulations described herein, 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1-Carboxylate is the hydrochloride.

In certain embodiments of the pharmaceutical formulations described herein, 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1-Carboxylate is a fumarate.

It should be understood that reference to a pharmaceutically acceptable salt includes solvent addition forms (solvates). Solvates contain stoichiometric or non-stoichiometric amounts of solvent and are formed by the formation or isolation of the product with pharmaceutically acceptable solvents such as water, ethanol, methanol, methyl tert-butyl ether (MTBE), diisopropyl ether (DIPE), ethyl acetate, isopropyl acetate, isopropyl alcohol , methyl isobutyl ketone (MIBK), methyl ethyl ketone (MEK), acetone, nitromethane, tetrahydrofuran (THF), dichloromethane (DCM), dioxane, heptanes, toluene, anisole, acetonitrile, etc. In one aspect, solvates are formed using, but not limited to, Class 3 solvent(s). Categories of solvents are defined, for example, in the International Conference on Harmonization of Technical Requirements for Registration of Medicinal Products for Human Use (ICH), Impurities: Residual Solvent Guidelines, Q3C (R3) (November 2005). Hydrates form when the solvent is water, or alcoholates form when the solvent is alcohol.

In some embodiments, solvates of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate or pharmaceutical thereof acceptable salts are conveniently prepared or formed by the processes described herein. In some embodiments, the 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate solvates are anhydrous. In some embodiments, 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl)benzyl)piperazine-1-carboxylate, or pharmaceutically acceptable thereof salts exist in unsolvated form. In some embodiments, 1,1,1,3,3,3hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate or pharmaceutically acceptable salts thereof exist in unsolvated form and are anhydrous.

In still other embodiments, 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate, or pharmaceutical thereof the acceptable salt is obtained in a variety of forms, including, but not limited to, amorphous phase, crystalline forms, particulate forms, and nanoparticles. In some embodiments, 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 carboxylate, or a pharmaceutically acceptable compound thereof the salt is amorphous. In some embodiments, 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate, or pharmaceutical thereof an acceptable salt is amorphous and anhydrous. In some embodiments, 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate, or a pharmaceutically acceptable compound thereof salt is crystalline. In some embodiments, 1,1,1,3,3,3hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate, or a pharmaceutically acceptable salt thereof is crystalline and anhydrous.

Although not intended to be limited by any particular theory, some solid forms have physical properties (eg, stability, solubility, and dissolution rate) suitable for pharmaceutical and therapeutic dosage forms. Moreover, without being bound by any particular theory, certain solid forms are characterized by physical properties (e.g., density, compressibility, hardness, morphology, cleavage, stickiness, solubility, water absorption, electrical properties, thermal properties, solid state reactivity, physical stability and chemical stability) affecting specific processes (eg, yield, filtration, washing, drying, grinding, mixing, tableting, flow, dissolution, formulation and lyophilization) that make certain solid forms suitable for the manufacture of solid dosage form. Such properties can be determined using specific analytical chemical techniques, including solid phase analytical techniques (eg, X-ray diffraction, microscopy, spectroscopy and thermal analysis), as described herein and known in the art.

As used herein, the terms effective amount or therapeutically effective amount refer to a sufficient amount of an agent or compound administered that will reduce to some extent one or more symptoms of the disease or condition being treated. The result may be a reduction and/or alleviation of signs, symptoms or

- 5 045280 causes of disease or any other desired change in a biological system. For example, an effective amount for therapeutic use is the amount of a composition containing a compound described herein necessary to provide a clinically significant reduction in disease. The appropriate effective amount in any particular case can be determined using methods such as dose escalation studies.

Pharmaceutical compounds.

The pharmaceutical compositions of 1,1,1,3,3,3-hexafluoropropan-2yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate described herein contain 1. 1,1,3,3,3hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient in solid dosage form.

In some embodiments, the pharmaceutical compositions described herein comprise 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine -1-carboxylate or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient in a solid dosage form, wherein the solid dosage form is selected from powder, tablet, bite disintegrating tablet, chewable tablet, capsular tablet, capsule, gelatin capsule, effervescent powder, rapid disintegrating tablet, anti-abuse tablet, modified-release tablet, modified-release capsule-shaped tablet, modified-release capsule, and powder-derived aqueous suspension.

In some embodiments, the pharmaceutical compositions described herein comprise 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine -1-carboxylate or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient in a solid dosage form, wherein the solid dosage form is a tablet.

In some embodiments, the pharmaceutical compositions described herein comprise 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine -1-carboxylate or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient in a solid dosage form, wherein the solid dosage form is a capsule-shaped tablet. In some embodiments, the pharmaceutical compositions described herein comprise 1,1,1,3,3,3hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1 -carboxylate or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient in a solid dosage form, wherein the solid dosage form is a capsule.

In some embodiments, a pharmaceutical composition is provided in solid dosage form, comprising:

(a) about 1 to about 60 mg 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl)benzyl)piperazine-1 -carboxylate or a pharmaceutically acceptable salt thereof;

(b) from about 5 to about 425 mg of polymer carrier;

(c) from about 0.2 to about 10 mg of surfactant; and (d) from about 0.2 to about 10 mg of glidant.

In certain embodiments described herein, the polymeric carrier is selected from polyvinylpyrrolidone K30 (PVP K30), polyvinylpyrrolidone K17 (PVP K17), polyvinylpyrrolidone K12 (PVP K12), polyvinylpyrrolidone/vinyl acetate (PVPVA 64), hydroxypropyl methylcellulose (HPMC), hydroxypropyl methylcellulose acetyl succinate (HP MS AS) and methyl methacrylate polymers (Eudragit polymers). In some embodiments, the polymeric carrier is polyvinylpyrrolidone K30 (PVP K30). In some embodiments described herein, the polymeric carrier is polyvinylpyrrolidone K17 (PVP K17). In some embodiments described herein, the polymeric carrier is polyvinylpyrrolidone/vinyl acetate (PVPVA 64). In some embodiments described herein, the polymeric carrier is hydroxypropyl methylcellulose (HPMC). In some embodiments described herein, the polymeric carrier is hydroxypropyl methylcellulose acetyl succinate (HPMC AS). In some embodiments described herein, the polymer carrier is methyl methacrylate polymers (Eudragit polymers).

In some embodiments, the pharmaceutical composition contains from about 5 to about 425 mg of polymeric carrier. In some embodiments, the pharmaceutical composition contains from about 5 to about 350 mg of polymeric carrier. In some embodiments, the pharmaceutical composition contains from about 5 to about 300 mg of polymeric carrier. In some embodiments, the pharmaceutical composition contains from about 5 to about

- 6 045280

250 mg polymer carrier. In some embodiments, the pharmaceutical composition contains from about 5 to about 200 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains from about 5 to about 175 mg of polymeric carrier. In some embodiments, the pharmaceutical composition contains from about 5 to about 150 mg of polymeric carrier. In some embodiments, the pharmaceutical composition contains from about 10 to about 150 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains from about 10 to about 125 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains from about 10 to about 100 mg of polymeric carrier. In some embodiments, the pharmaceutical composition contains from about 10 to about 95 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains from about 10 to about 90 mg of polymeric carrier. In some embodiments, the pharmaceutical composition contains from about 12 to about 90 mg of polymeric carrier. In some embodiments, the pharmaceutical composition contains from about 10 to about 85 mg of polymeric carrier. In some embodiments, the pharmaceutical composition contains from about 12 to about 85 mg of polymeric carrier. In some embodiments, the pharmaceutical composition contains from about 12 to about 80 mg of polymeric carrier. In some embodiments, the pharmaceutical composition contains from about 14 to about 80 mg of polymeric carrier. In some embodiments, the pharmaceutical composition contains from about 12 to about 75 mg of polymeric carrier. In some embodiments, the pharmaceutical composition contains from about 14 to about 75 mg of polymeric carrier. In some embodiments, the pharmaceutical composition contains about 5 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 10 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 11 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 12 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 13 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 14 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 15 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 16 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 17 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 18 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 19 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 20 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 25 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 30 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 35 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 40 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 45 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 50 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 55 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 60 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 65 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 70 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 75 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 80 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 85 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 90 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 95 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains about 100 mg of polymer carrier. In some embodiments, the pharmaceutical composition contains from about 10 to about 90 mg of a polymeric carrier, wherein the polymeric carrier is polyvinylpyrrolidone K30 (PVP K30). In some embodiments, the pharmaceutical composition contains from about 10 to about 90 mg of a polymeric carrier, wherein the polymeric carrier is polyvinylpyrrolidone K17 (PVP K17). In some embodiments, the pharmaceutical composition contains from about 10 to about 90 mg of a polymeric carrier, wherein the polymeric carrier is polyvinylpyrrolidone K12 (PVP K12). In some embodiments, the pharmaceutical composition contains from about 10 to about 90 mg of a polymeric carrier, wherein the polymeric carrier is polyvinylpyrrolidone/vinyl acetate (PVPVA 64). According to some

- 7 045280 In other embodiments, the pharmaceutical composition contains from about 10 to about 90 mg of a polymeric carrier, wherein the polymeric carrier is hydroxypropyl methylcellulose (HPMC). In some embodiments, the pharmaceutical composition contains from about 10 to about 90 mg of a polymeric carrier, wherein the polymeric carrier is hydroxypropyl methylcellulose acetyl succinate (HPMC AS). In some embodiments, the pharmaceutical composition contains from about 10 to about 90 mg of a polymeric carrier, wherein the polymeric carrier is methyl methacrylate polymers (Eudragit polymers).

In some embodiments, the surfactant is selected from polysorbates, polaxomers, bile salts, glyceryl monostearate, sodium lauryl sulfate, sorbitan monooleate, polyoxyethylene sorbitan monooleate, ethylene oxide-propylene oxide copolymers, and d-a-tocopheryl polyethylene glycol succinate (Vitamin E TPGS). In some embodiments, the surfactant is a polysorbate. In some embodiments, the surfactant is polysorbate 80 (Tween 80). In some embodiments, the surfactant is a polaxomer. In some embodiments, the surfactant is a bile salt. In some embodiments, the surfactant is glyceryl monostearate. In some embodiments, the surfactant is sodium lauryl sulfate. In some embodiments, the surfactant is sorbitan monooleate. In some embodiments, the surfactant is polyoxyethylene sorbitan monooleate. In some embodiments, the surfactant is an ethylene oxide copolymer. In some embodiments, the surfactant is a propylene oxide copolymer. In some embodiments, the surfactant is d-a-tocopheryl polyethylene glycol succinate (vitamin E TPGS). In some embodiments, the pharmaceutical composition contains from about 0.2 to about 10 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 8 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 7 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 6 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 5 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 4 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 3.5 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 3 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 2.5 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 2 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 1.5 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 1 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 5 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 4 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 3.5 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 3 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 2.5 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 2 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 1.5 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 1 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 5 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 4 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 3.5 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 3 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 2.5 mg of surfactant. In some embodiments, the pharmaceutical composition comprises

- 8 045280 from about 0.4 to about 2 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 1.5 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 1 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 0.2 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 0.25 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 0.3 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 0.35 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 0.4 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 0.45 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 0.5 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 0.6 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 0.7 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 0.8 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 0.9 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 1 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 1.1 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 1.2 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 1.3 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 1.4 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 1.5 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 1.6 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 1.7 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 1.8 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 1.9 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 2 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 2.25 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 2.5 mg of surfactant.

In some embodiments, the pharmaceutical composition contains about 2.75 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 3 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 3.5 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 4 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 4.5 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 5 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 6 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 7 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 8 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 9 mg of surfactant. In some embodiments, the pharmaceutical composition contains about 10 mg of surfactant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 10 mg of a surfactant, wherein the surfactant is polysorbate 80 (Tween 80). In some embodiments, the pharmaceutical composition contains from about 0.2 to about 5 mg of a surfactant, wherein the surfactant is polysorbate 80 (Tween 80). In some embodiments, the pharmaceutical composition contains from about 0.2 to about 4 mg of a surfactant, wherein the surfactant is polysorbate 80 (Tween 80). In some embodiments, the pharmaceutical composition contains from about 0.2 to about 3 mg of a surfactant, wherein the surfactant is polysorbate 80 (Tween 80). In some embodiments, the pharmaceutical composition contains from about 0.2 to about 2.5 mg of a surfactant, wherein the surfactant is polysorbate 80 (Tween 80). In some embodiments, the pharmaceutical composition contains from about 0.2 to about 2 mg of surfactant, with

- 9 045280 The active substance is polysorbate 80 (Tween 80). In some embodiments, the pharmaceutical composition contains from about 0.4 to about 4 mg of a surfactant, wherein the surfactant is polysorbate 80 (Tween 80). In some embodiments, the pharmaceutical composition contains from about 0.4 to about 3 mg of a surfactant, wherein the surfactant is polysorbate 80 (Tween 80). In some embodiments, the pharmaceutical composition contains from about 0.4 to about 2.5 mg of a surfactant, wherein the surfactant is polysorbate 80 (Tween 80). In some embodiments, the pharmaceutical composition contains from about 0.4 to about 2 mg of a surfactant, wherein the surfactant is polysorbate 80 (Tween 80).

In some embodiments, the glidant is silica or talc. In some embodiments, the glidant is talc. In some embodiments, the glidant is silica. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 10 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 8 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 7 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 6 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 5 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 4 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 3.5 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 3 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 2.5 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 2 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 1.5 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 1 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 5 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 4 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 3.5 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 3 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 2.5 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 2 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 1.5 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 1 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 5 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 4 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 3.5 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 3 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 2.5 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 2 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 1.5 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 1 mg of glidant. In some embodiments, the pharmaceutical composition contains about 0.2 mg of glidant. In some embodiments, the pharmaceutical composition contains about 0.25 mg of glidant. In some embodiments, the pharmaceutical composition contains about 0.3 mg of glidant. In some embodiments, the pharmaceutical composition contains about 0.35 mg of glidant. In some embodiments, the pharmaceutical composition contains about 0.4 mg of glidant. In some embodiments, the pharmaceutical composition contains about 0.45 mg of glidant. In some embodiments, the pharmaceutical composition contains about 0.5 mg of glidant. In some embodiments, the pharmaceutical composition contains about 0.6 mg of glidant. In some embodiments, the pharmaceutical composition contains about 0.7 mg of glidant. In some embodiments, the pharmaceutical composition contains about 0.8 mg of glidant. In some embodiments, the pharmaceutical composition contains about 0.9 mg of glidant. In some embodiments, the pharmaceutical composition contains about 1 mg of glidant. In some embodiments, the pharmaceutical composition contains about 1.1 mg of glidant. In some embodiments, the pharmaceutical composition contains about 1.2 mg of glidant. In some embodiments, the pharmaceutical composition contains about 1.3 mg of glidant. According to some

- 10 045280 embodiments, the pharmaceutical composition contains about 1.4 mg of glidant. In some embodiments, the pharmaceutical composition contains about 1.5 mg of glidant. In some embodiments, the pharmaceutical composition contains about 1.6 mg of glidant. In some embodiments, the pharmaceutical composition contains about 1.7 mg of glidant. In some embodiments, the pharmaceutical composition contains about 1.8 mg of glidant. In some embodiments, the pharmaceutical composition contains about 1.9 mg of glidant. In some embodiments, the pharmaceutical composition contains about 2 mg of glidant. In some embodiments, the pharmaceutical composition contains about 2.25 mg of glidant. In some embodiments, the pharmaceutical composition contains about 2.5 mg of glidant. In some embodiments, the pharmaceutical composition contains about 2.75 mg of glidant. In some embodiments, the pharmaceutical composition contains about 3 mg of glidant. In some embodiments, the pharmaceutical composition contains about 3.5 mg of glidant. In some embodiments, the pharmaceutical composition contains about 4 mg of glidant. In some embodiments, the pharmaceutical composition contains about 4.5 mg of glidant. In some embodiments, the pharmaceutical composition contains about 5 mg of glidant. In some embodiments, the pharmaceutical composition contains about 6 mg of glidant. In some embodiments, the pharmaceutical composition contains about 7 mg of glidant. In some embodiments, the pharmaceutical composition contains about 8 mg of glidant. In some embodiments, the pharmaceutical composition contains about 9 mg of glidant. In some embodiments, the pharmaceutical composition contains about 10 mg of glidant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 10 mg of a glidant, wherein the glidant is silica. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 5 mg of a glidant, wherein the glidant is silica. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 4 mg of a glidant, wherein the glidant is silica. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 3 mg of a glidant, wherein the glidant is silica. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 2.5 mg of a glidant, wherein the glidant is silica. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 2 mg of a glidant, wherein the glidant is silica. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 4 mg of a glidant, wherein the glidant is silica. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 3 mg of glidant, wherein the glidant is silica. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 2.5 mg of a glidant, wherein the glidant is silica. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 2 mg of glidant, wherein the glidant is silica. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 10 mg of a glidant, wherein the glidant is talc. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 5 mg of a glidant, wherein the glidant is talc. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 4 mg of a glidant, wherein the glidant is talc. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 3 mg of a glidant, wherein the glidant is talc. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 2.5 mg of a glidant, wherein the glidant is talc. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 2 mg of a glidant, wherein the glidant is talc. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 4 mg of a glidant, wherein the glidant is talc. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 3 mg of a glidant, wherein the glidant is talc. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 2.5 mg of a glidant, wherein the glidant is talc. In some embodiments, the pharmaceutical composition contains from about 0.4 to about 2 mg of a glidant, wherein the glidant is talc.

In some embodiments, the pharmaceutical composition further comprises a buffer. In some embodiments, the pharmaceutical composition further comprises a buffer selected from acetates, carbonates, phosphates, citrates and glutamates. In some embodiments, the pharmaceutical composition further comprises an acetate buffer. In some embodiments, the pharmaceutical composition further comprises a carbonate buffer. In some embodiments, the pharmaceutical composition further comprises a phosphate buffer. In some embodiments, the pharmaceutical composition further comprises a citrate buffer. According to some embodiments of the pharmaceutical

- 11 045280 chemical composition additionally contains a glutamate buffer. In some embodiments, the pharmaceutical composition further comprises a buffer selected from potassium dihydrogen phosphate, sodium bicarbonate, magnesium carbonate, sodium citrate, sodium dihydrogen phosphate, dipotassium monohydrogen phosphate, and disodium monohydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises a buffer selected from potassium dihydrogen phosphate, sodium bicarbonate, magnesium carbonate, and sodium citrate. In some embodiments, the pharmaceutical composition further comprises a buffer selected from potassium dihydrogen phosphate, sodium bicarbonate, magnesium carbonate, sodium citrate, sodium dihydrogen phosphate, dipotassium monohydrogen phosphate, and disodium monohydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises sodium dihydrogen phosphate, dipotassium monohydrogen phosphate, and disodium monohydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises dipotassium monohydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises disodium monohydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises from about 0.1 to about 5 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 4.5 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises from about 0.1 to about 4 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 3.5 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises from about 0.1 to about 3 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 2.5 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises from about 0.1 to about 2 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 1.5 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises from about 0.1 to about 1 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further contains from about 0.1 mg to about 0.5 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises from about 0.2 to about 4 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 3.5 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises from about 0.2 to about 3 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 2.5 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises from about 0.2 to about 2 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 1.5 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises from about 0.2 to about 1 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further contains from about 0.2 mg to about 0.5 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises about 0.1 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises about 0.15 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises about 0.2 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises about 0.25 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises about 0.3 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises about 0.35 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises about 0.4 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises about 0.45 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises about 0.5 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises about 0.55 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises about 0.6 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises about 0.65 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises about 0.7 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises about 0.75 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises about 0.8 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises about 0.85 mg of potassium dihydrogen phosphate. According to some options

- 12 045280 there, the pharmaceutical composition additionally contains about 0.9 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises about 0.95 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further contains about 1 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises about 1.25 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises about 1.5 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises about 1.75 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further contains about 2 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises about 2.5 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further contains about 3 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises about 3.5 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further contains about 4 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further comprises about 4.5 mg of potassium dihydrogen phosphate. In some embodiments, the pharmaceutical composition further contains about 5 mg of potassium dihydrogen phosphate.

In some embodiments, the pharmaceutical composition further comprises sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 5 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 4.5 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 4 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 3.5 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 3 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 2.5 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 2 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 1.5 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 1 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 0.5 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 4 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 3.5 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 3 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 2.5 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 2 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 1.5 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 1 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 0.5 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 0.1 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 0.15 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 0.2 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 0.25 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 0.3 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 0.35 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 0.4 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 0.45 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 0.5 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 0.55 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 0.6 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 0.65 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 0.7 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further comprises about

- 13 045280

0.75 mg sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 0.8 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 0.85 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 0.9 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 0.95 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 1 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 1.25 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 1.5 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 1.75 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 2 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 2.5 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 3 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 3.5 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 4 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 4.5 mg of sodium bicarbonate. In some embodiments, the pharmaceutical composition further contains about 5 mg of sodium bicarbonate.

In some embodiments, the pharmaceutical composition further comprises magnesium carbonate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 5 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 4.5 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 4 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 3.5 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 3 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 2.5 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 2 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 1.5 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 1 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 0.5 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 4 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 3.5 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 3 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 2.5 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 2 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 1.5 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 1 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 0.5 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 0.1 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further comprises about 0.15 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 0.2 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 0.25 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 0.3 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 0.35 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 0.4 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 0.45 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 0.5 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 0.55 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 0.6 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 0.65 mg of magnesium carbonate. Co

- 14 045280 In some embodiments, the pharmaceutical composition additionally contains about 0.7 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 0.75 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 0.8 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 0.85 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 0.9 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 0.95 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 1 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 1.25 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 1.5 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 1.75 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 2 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 2.5 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 3 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 3.5 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 4 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 4.5 mg of magnesium carbonate. In some embodiments, the pharmaceutical composition further contains about 5 mg of magnesium carbonate.

In some embodiments, the pharmaceutical composition further comprises sodium citrate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 5 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 4.5 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 4 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 3.5 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 3 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 2.5 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 2 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 1.5 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 1 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 0.5 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 4 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 3.5 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 3 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 2.5 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 2 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 1.5 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 1 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 0.5 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 0.1 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 0.15 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 0.2 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 0.25 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 0.3 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 0.35 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 0.4 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 0.45 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 0.5 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 0.55 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 0.6 mg of citrate per

- 15 045280 tria. In some embodiments, the pharmaceutical composition further contains about 0.65 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 0.7 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 0.75 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 0.8 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 0.85 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 0.9 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 0.95 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 1 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 1.25 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 1.5 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 1.75 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 2 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 2.5 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 3 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 3.5 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 4 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 4.5 mg of sodium citrate. In some embodiments, the pharmaceutical composition further contains about 5 mg of sodium citrate.

In some embodiments, the pharmaceutical composition further comprises a plasticizer. In some embodiments, the plasticizer is selected from PEG-400, triethyl citrate, triacetin, acetyl tributyl citrate, acetyl triethyl citrate, stearic acid, glycerin, polyethylene glycols, polyethylene glycol monomethyl ether, propylene glycol, sorbitan sorbitol solution, castor oil, diacetylated monoglycerides, dibutyl seb cinate and diethyl phthalate. In some embodiments, the pharmaceutical composition further comprises a plasticizer, wherein the plasticizer is PEG-400. In some embodiments, the pharmaceutical composition further comprises a plasticizer, wherein the plasticizer is triethyl citrate. In some embodiments, the pharmaceutical composition further comprises a plasticizer, wherein the plasticizer is triacetin. In some embodiments, the pharmaceutical composition further comprises a plasticizer, wherein the plasticizer is acetyltributyl citrate. In some embodiments, the pharmaceutical composition further comprises a plasticizer, wherein the plasticizer is acetyl triethyl citrate. In some embodiments, the pharmaceutical composition further comprises a plasticizer, wherein the plasticizer is stearic acid. In some embodiments, the pharmaceutical composition further comprises a plasticizer, wherein the plasticizer is glycerol. In some embodiments, the pharmaceutical composition further comprises a plasticizer, wherein the plasticizer is polyethylene glycol. In some embodiments, the pharmaceutical composition further comprises a plasticizer, wherein the plasticizer is polyethylene glycol monomethyl ether. In some embodiments, the pharmaceutical composition further comprises a plasticizer, wherein the plasticizer is propylene glycol. In some embodiments, the pharmaceutical composition further comprises a plasticizer, wherein the plasticizer is a sorbitan-sorbitol solution. In some embodiments, the pharmaceutical composition further comprises a plasticizer, wherein the plasticizer is castor oil. In some embodiments, the pharmaceutical composition further comprises a plasticizer, wherein the plasticizer is diacetylated monoglycerides. In some embodiments, the pharmaceutical composition further comprises a plasticizer, wherein the plasticizer is dibutyl sebacate. In some embodiments, the pharmaceutical composition further comprises a plasticizer, wherein the plasticizer is diethyl phthalate. In some embodiments, the pharmaceutical composition further contains from about 1 to about 65 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains from about 1 to about 60 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains from about 1 to about 55 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains from about 1 to about 50 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains from about 1 to about 45 mg of plasticizer. According to some embodiments, pharmaceutical

- 16 045280 composition additionally contains from about 1 to about 40 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains from about 1 to about 35 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains from about 1 to about 30 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains from about 1 to about 25 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains from about 1 to about 20 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains from about 1 to about 15 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains from about 1 to about 10 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains from about 2 to about 30 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains from about 2 to about 25 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains from about 2 to about 20 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains from about 2 to about 15 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains from about 2 to about 10 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains about 1 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains about 1.5 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains about 2 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains about 2.5 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains about 3 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains about 3.5 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains about 4 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains about 4.5 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains about 5 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains about 5.5 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains about 6 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains about 6.5 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains about 7 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains about 7.5 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains about 8 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains about 8.5 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains about 9 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains about 10 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains about 11 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains about 12 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains about 13 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains about 14 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains about 15 mg of plasticizer. In some embodiments, the pharmaceutical composition further contains from about 1 to about 65 mg of a plasticizer, wherein the plasticizer is PEG-400. In some embodiments, the pharmaceutical composition further contains from about 1 to about 60 mg of a plasticizer, wherein the plasticizer is PEG-400. In some embodiments, the pharmaceutical composition further contains from about 1 to about 55 mg of a plasticizer, wherein the plasticizer is PEG-400. In some embodiments, the pharmaceutical composition further contains from about 1 to about 50 mg of a plasticizer, wherein the plasticizer is PEG-400. In some embodiments, the pharmaceutical composition further contains from about 1 to about 45 mg of a plasticizer, wherein the plasticizer is PEG-400. In some embodiments, the pharmaceutical composition further contains from about 1 to about 40 mg of a plasticizer, wherein the plasticizer is PEG-400. In some embodiments, the pharmaceutical composition further contains from about 1 to about 35 mg of a plasticizer, wherein the plasticizer is PEG-400. In some embodiments, the pharmaceutical composition further contains from about 1 to about 30 mg of a plasticizer, wherein the plasticizer is PEG-400. In some embodiments, the pharmaceutical composition further contains from about 1 to about 25 mg of a plasticizer, wherein the plasticizer is PEG-400.

- 17 045280

In some embodiments, the pharmaceutical composition further contains from about 1 to about 20 mg of a plasticizer, wherein the plasticizer is PEG-400. In some embodiments, the pharmaceutical composition further contains from about 1 to about 15 mg of a plasticizer, wherein the plasticizer is PEG-400. In some embodiments, the pharmaceutical composition further contains from about 1 to about 10 mg of a plasticizer, wherein the plasticizer is PEG-400. In some embodiments, the pharmaceutical composition further contains from about 2 to about 30 mg of a plasticizer, wherein the plasticizer is PEG-400. In some embodiments, the pharmaceutical composition further contains from about 2 to about 25 mg of a plasticizer, wherein the plasticizer is PEG-400. In some embodiments, the pharmaceutical composition further contains from about 2 to about 20 mg of a plasticizer, wherein the plasticizer is PEG-400. In some embodiments, the pharmaceutical composition further contains from about 2 to about 15 mg of a plasticizer, wherein the plasticizer is PEG-400. In some embodiments, the pharmaceutical composition further contains from about 2 to about 10 mg of a plasticizer, wherein the plasticizer is PEG 400.

In some embodiments, the pharmaceutical composition further comprises an excipient. In some embodiments, the filler is selected from lactose, mannitol, dicalcium phosphate, microcrystalline cellulose, siliconized microcrystalline cellulose, starch, and pregelatinized starch (1500 starch). In some embodiments, the filler is lactose. In some embodiments, the excipient is mannitol. In some embodiments, the filler is dicalcium phosphate. In some embodiments, the filler is microcrystalline cellulose. In some embodiments, the filler is siliconized microcrystalline cellulose. In some embodiments, the filler is starch. In some embodiments, the filler is pregelatinized starch (1500 starch). In some embodiments, the pharmaceutical composition further contains from about 15 to about 850 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 15 to about 800 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 15 to about 750 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 15 to about 700 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 15 to about 650 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 15 to about 600 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 15 to about 550 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 15 to about 500 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 15 to about 450 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 15 to about 400 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 20 to about 400 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 20 to about 350 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 20 to about 300 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 20 to about 275 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 20 to about 250 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 20 to about 225 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 20 to about 200 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 25 to about 300 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 25 to about 275 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 25 to about 250 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 25 to about 225 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 25 to about 200 mg of excipient. In some embodiments, the filler is selected from lactose, mannitol, dicalcium phosphate, microcrystalline cellulose, siliconized microcrystalline cellulose, starch, and pregelatinized starch (1500 starch). In some embodiments, the pharmaceutical composition further contains from about 30 to about 300 mg of excipient. According to some

- 18 045280 embodiments, the pharmaceutical composition further contains from about 30 to about 275 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 30 to about 250 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 30 to about 225 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 30 to about 200 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 30 to about 175 mg of excipient. In some embodiments, the pharmaceutical composition further contains from about 30 to about 150 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 30 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 35 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 40 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 45 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 50 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 55 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 60 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 65 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 70 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 75 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 80 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 85 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 90 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 95 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 100 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 105 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 110 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 115 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 120 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 125 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 130 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 135 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 140 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 145 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 150 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 155 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 160 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 165 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 170 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 175 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 180 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 185 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 190 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 195 mg of excipient. In some embodiments, the pharmaceutical composition further contains about 200 mg of excipient.

In some embodiments, the pharmaceutical composition further comprises a disintegrant. In some embodiments, the disintegrant is selected from corn starch, potato starch, microcrystalline cellulose, methylcellulose, croscarmellose sodium, sodium starch glycolate, povidone, crospovidone, hypromellose, hydroxypropylcellulose, polyvinyl alcohol, alginic acid, sodium alginate, agar, guar, locust bean, karaia , pectin, tragacanth, bentonite, citrus pulp and sodium lauryl sulfate. In some embodiments, the disintegrant is selected from povidone, crospovidone, hypromellose, croscarmellose sodium, hydroxypropylcellulose, and polyvinyl alcohol. In some embodiments, the disintegrant is polyvinyl alcohol. In some embodiments, the disintegrant is hydroxypropylcellulose. In some embodiments, the leavening agent is hypromellose. According to some options

- 19 045280 there the baking powder is povidone. In some embodiments, the disintegrant is crospovidone. In some embodiments, the leavening agent is croscarmellose sodium. In some embodiments, the pharmaceutical composition further contains from about 3 to about 150 mg of a disintegrant. In some embodiments, the pharmaceutical composition further contains from about 3 to about 125 mg of a disintegrant. In some embodiments, the pharmaceutical composition further contains from about 3 to about 100 mg of a disintegrant. In some embodiments, the pharmaceutical composition further contains from about 3 to about 75 mg of a disintegrant. In some embodiments, the pharmaceutical composition further contains from about 3 to about 60 mg of a disintegrant. In some embodiments, the pharmaceutical composition further contains from about 3 to about 50 mg of a disintegrant. In some embodiments, the pharmaceutical composition further contains from about 4 to about 60 mg of a disintegrant. In some embodiments, the pharmaceutical composition further contains from about 4 to about 55 mg of a disintegrant. In some embodiments, the pharmaceutical composition further contains from about 4 to about 50 mg of a disintegrant. In some embodiments, the pharmaceutical composition further contains from about 5 to about 50 mg of a disintegrant. In some embodiments, the pharmaceutical composition further contains from about 5 to about 45 mg of a disintegrant. In some embodiments, the pharmaceutical composition further contains from about 5 to about 40 mg of a disintegrant. In some embodiments, the pharmaceutical composition further contains from about 5 to about 35 mg of a disintegrant. In some embodiments, the pharmaceutical composition further contains from about 5 to about 30 mg of a disintegrant. In some embodiments, the pharmaceutical composition further contains from about 6 to about 30 mg of a disintegrant. In some embodiments, the pharmaceutical composition further contains about 5 mg of disintegrant. In some embodiments, the pharmaceutical composition further contains about 6 mg of disintegrant. In some embodiments, the pharmaceutical composition further contains about 7 mg of disintegrant. In some embodiments, the pharmaceutical composition further contains about 8 mg of disintegrant. In some embodiments, the pharmaceutical composition further contains about 9 mg of disintegrant. In some embodiments, the pharmaceutical composition further contains about 10 mg of disintegrant. In some embodiments, the pharmaceutical composition further contains about 12 mg of disintegrant. In some embodiments, the pharmaceutical composition further contains about 15 mg of disintegrant. In some embodiments, the pharmaceutical composition further contains about 20 mg of disintegrant. In some embodiments, the pharmaceutical composition further contains about 25 mg of disintegrant. In some embodiments, the pharmaceutical composition further contains about 30 mg of disintegrant. In some embodiments, the pharmaceutical composition further contains about 35 mg of disintegrant. In some embodiments, the pharmaceutical composition further contains about 40 mg of disintegrant. In some embodiments, the pharmaceutical composition further contains from about 3 to about 150 mg of a disintegrant, wherein the disintegrant is crospovidone. In some embodiments, the pharmaceutical composition further contains from about 3 to about 100 mg of a disintegrant, wherein the disintegrant is crospovidone. In some embodiments, the pharmaceutical composition further contains from about 3 to about 75 mg of a disintegrant, wherein the disintegrant is crospovidone. In some embodiments, the pharmaceutical composition further contains from about 3 to about 60 mg of a disintegrant, wherein the disintegrant is crospovidone. In some embodiments, the pharmaceutical composition further contains from about 5 to about 50 mg of a disintegrant, wherein the disintegrant is crospovidone. In some embodiments, the pharmaceutical composition further contains from about 5 to about 40 mg of a disintegrant, wherein the disintegrant is crospovidone. In some embodiments, the pharmaceutical composition further contains from about 5 to about 35 mg of a disintegrant, wherein the disintegrant is crospovidone. In some embodiments, the pharmaceutical composition further contains from about 5 to about 30 mg of a disintegrant, wherein the disintegrant is crospovidone. In some embodiments, the pharmaceutical composition further contains from about 5 to about 30 mg of a disintegrant, wherein the disintegrant is crospovidone. In some embodiments, the pharmaceutical composition further contains from about 3 to about 100 mg of a disintegrant, wherein the disintegrant is croscarmellose sodium. In some embodiments, the pharmaceutical composition further contains from about 3 to about 75 mg of a disintegrant, wherein the disintegrant is croscarmellose sodium. In some embodiments, the pharmaceutical composition further contains from about 3 to about 60 mg of a disintegrant, wherein the disintegrant is

- 20 045280 is croscarmellose sodium. In some embodiments, the pharmaceutical composition further contains from about 5 to about 50 mg of a disintegrant, wherein the disintegrant is croscarmellose sodium. In some embodiments, the pharmaceutical composition further contains from about 5 to about 40 mg of a disintegrant, wherein the disintegrant is croscarmellose sodium. In some embodiments, the pharmaceutical composition further contains from about 5 to about 35 mg of a disintegrant, wherein the disintegrant is croscarmellose sodium. In some embodiments, the pharmaceutical composition further contains from about 5 to about 30 mg of a disintegrant, wherein the disintegrant is croscarmellose sodium. In some embodiments, the pharmaceutical composition further contains from about 5 to about 30 mg of a disintegrant, wherein the disintegrant is croscarmellose sodium.

In some embodiments, the pharmaceutical composition further comprises a lubricant. In some embodiments, the lubricant is selected from magnesium stearate, stearic acid, and sodium stearyl fumarate. In some embodiments, the lubricant is stearic acid. In some embodiments, the lubricant is sodium stearyl fumarate. In some embodiments, the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 10 mg of lubricant. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 8 mg of lubricant. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 6 mg of lubricant. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 5 mg of a lubricant. In some embodiments, the pharmaceutical composition further contains from about 0.1 to about 4 mg of lubricant. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 10 mg of lubricant. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 8 mg of lubricant. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 7 mg of lubricant. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 6 mg of lubricant. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 5 mg of lubricant. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 4 mg of lubricant. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 3.5 mg of lubricant. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 3 mg of lubricant. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 2.5 mg of lubricant. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 2 mg of lubricant. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 1.5 mg of lubricant. In some embodiments, the pharmaceutical composition further contains from about 0.3 to about 3 mg of lubricant. In some embodiments, the pharmaceutical composition further contains from about 0.3 to about 2.5 mg of lubricant. In some embodiments, the pharmaceutical composition further contains from about 0.3 to about 2 mg of lubricant. In some embodiments, the pharmaceutical composition further contains from about 0.3 to about 1.5 mg of lubricant. In some embodiments, the pharmaceutical composition further contains from about 0.3 to about 1 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 0.1 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 0.15 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 0.2 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 0.25 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 0.3 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 0.35 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 0.4 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 0.45 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 0.5 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 0.6 mg of lubricant. According to some options

- 21 045280 implementation of the pharmaceutical composition additionally contains about 0.7 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 0.8 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 0.9 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 1 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 1.1 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 1.2 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 1.3 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 1.4 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 1.5 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 1.6 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 1.7 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 1.8 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 1.9 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 2 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 2.5 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 3 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 4 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 5 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 6 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 7 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 8 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 9 mg of lubricant. In some embodiments, the pharmaceutical composition further contains about 10 mg of lubricant. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 10 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 5 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 4 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 3 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 2.5 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 2 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 1.5 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 1 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition further contains from about 0.3 to about 4 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition further contains from about 0.3 to about 3 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition further contains from about 0.3 to about 2.5 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition further contains from about 0.3 to about 2 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition further contains from about 0.3 to about 1.5 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition further contains from about 0.3 to about 1 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. According to some embodiments

- 22 045280 the pharmaceutical composition further contains from about 0.2 to about 10 mg of a lubricant, the lubricant being magnesium stearate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 5 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 4 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 3 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 2.5 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 2 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 1.5 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition further contains from about 0.2 to about 1 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition further contains from about 0.3 to about 4 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition further contains from about 0.3 to about 3 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition further contains from about 0.3 to about 2.5 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition further contains from about 0.3 to about 2 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition further contains from about 0.3 to about 1.5 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition further contains from about 0.3 to about 1 mg of a lubricant, wherein the lubricant is magnesium stearate.

In some embodiments, 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate is in the free base form .

In some embodiments, the pharmaceutical composition contains from about 1 to about 60 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 55 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 50 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 45 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 40 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 35 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 30 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 25 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 20 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 15 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

- 23 045280

In some embodiments, the pharmaceutical composition contains from about 1 to about 10 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 30 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 25 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 20 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 15 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 10 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 1 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 1.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) free base benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 2 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 2.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) free base benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 3 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 3.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) free base benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 4 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 4.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) free base benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 6 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 7 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 8 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 9 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 10 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 11 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)-24 free base 045280 benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 12 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 13 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 14 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 15 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 16 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 17 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 18 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 19 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 20 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 25 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 30 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 35 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 40 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 45 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 50 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 55 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 60 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate is in a pharmaceutically acceptable form salt.

In some embodiments, 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate is the hydrochloride 1, 1,3,3,3hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 60 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-( trifluoromethyl)benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to

- 25 045280 about 55 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride - carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 50 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-( trifluoromethyl)benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 45 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-( trifluoromethyl)benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 40 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-( trifluoromethyl)benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 35 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) hydrochloride )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 30 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) hydrochloride )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 25 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) hydrochloride )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 20 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) hydrochloride )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 15 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) hydrochloride )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 10 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) hydrochloride )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 30 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) hydrochloride )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 25 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) hydrochloride )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 20 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) hydrochloride )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 15 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) hydrochloride )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 10 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) hydrochloride )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 1 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -carboxylate.

In some embodiments, the pharmaceutical composition contains about 1.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl hydrochloride )piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 2 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -carboxylate.

In some embodiments, the pharmaceutical composition contains about 2.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl hydrochloride )piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 3 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -carboxylate.

In some embodiments, the pharmaceutical composition contains about 3.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl hydrochloride )piperazine-1-carboxylate.

- 26 045280

In some embodiments, the pharmaceutical composition contains about 4 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -carboxylate.

In some embodiments, the pharmaceutical composition contains about 4.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl hydrochloride )piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -carboxylate.

In some embodiments, the pharmaceutical composition contains about 6 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -carboxylate.

In some embodiments, the pharmaceutical composition contains about 7 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -carboxylate.

In some embodiments, the pharmaceutical composition contains about 8 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 9 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -carboxylate.

In some embodiments, the pharmaceutical composition contains about 10 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 11 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 12 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 13 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 14 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 15 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 16 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 17 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 18 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 19 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 20 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl)benzyl)piperazine hydrochloride 1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 25 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 30 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 35 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)-hydrochloride 27 045280 piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 40 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 45 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 50 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 55 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 60 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -1-carboxylate.

In some embodiments, 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate is the fumarate 1, 1,1,3,3,3hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 60 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 55 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 50 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 45 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 40 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 35 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 30 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 25 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) fumarate) benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 20 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 15 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 10 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 30 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 25 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 20 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to

- 28 045280 about 15 mg 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate fumarate .

In some embodiments, the pharmaceutical composition contains from about 2 to about 10 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 1 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 1.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl fumarate )piperazine 1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 2 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 2.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl fumarate )piperazine 1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 3 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 3.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl fumarate )piperazine 1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 4 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 4.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl fumarate )piperazine 1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 6 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 7 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 8 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 9 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 10 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 11 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 12 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 13 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 14 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 15 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

- 29 045280

In some embodiments, the pharmaceutical composition contains about 16 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 17 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 18 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 19 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 20 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 25 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 30 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 35 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 40 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 45 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 50 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 55 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 60 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, described herein is a pharmaceutical composition in solid dosage form comprising:

(a) about 2 to about 12 mg 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride -carboxylate;

(b) from about 14 to about 72.5 mg of polyvinylpyrrolidone K30 (PVP K30);

(c) from about 2 to about 13 mg of PEG-400;

(d) from about 0.4 to about 2 mg of polysorbate 80 (Tween 80);

(e) from about 0.4 to about 2 mg of silicon dioxide;

(f) from about 0.2 to about 1 mg of potassium dihydrogen phosphate;

(g) from about 33 to about 170 mg microcrystalline cellulose;

(h) about 6 to about 30 mg of crospovidone; and (i) from about 0.3 to about 1.5 mg of sodium stearyl fumarate.

In some embodiments, described herein is a pharmaceutical composition in solid dosage form comprising:

(a) about 2 to about 12 mg 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride -carboxylate;

(b) about 17 to about 85 mg polyvinylpyrrolidone/vinyl acetate (PVPVA 64);

(c) about 0.4 to about 2 mg polysorbate 80 (Tween 80);

(d) from about 0.4 to about 2 mg of silicon dioxide;

(e) from about 0.2 to about 1 mg of potassium dihydrogen phosphate;

(f) from about 33 to about 170 mg microcrystalline cellulose;

(g) from about 6 to about 30 mg of crospovidone; and (h) from about 0.3 to about 1.5 mg of sodium stearyl fumarate.

- 30 045280

In some embodiments, described herein is a pharmaceutical composition in solid dosage form comprising:

(a) about 1 to about 60 mg 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl)benzyl)piperazine-1 -carboxylate or a pharmaceutically acceptable salt thereof;

(b) from about 20 to about 400 mg of excipient;

(c) from about 3 to about 150 mg of baking powder; and (d) from about 0.1 to about 10 mg of lubricant.

In some embodiments, the pharmaceutical composition contains an excipient. In some embodiments, the filler is selected from lactose, mannitol, dicalcium phosphate, microcrystalline cellulose, siliconized microcrystalline cellulose, starch, and pregelatinized starch (1500 starch). In some embodiments, the filler is lactose. In some embodiments, the excipient is mannitol. In some embodiments, the filler is dicalcium phosphate. In some embodiments, the filler is microcrystalline cellulose. In some embodiments, the filler is siliconized microcrystalline cellulose. In some embodiments, the filler is starch. In some embodiments, the filler is pregelatinized starch (1500 starch). In some embodiments, the pharmaceutical composition contains from about 20 to about 750 mg of excipient. In some embodiments, the pharmaceutical composition contains from about 20 to about 700 mg of excipient. In some embodiments, the pharmaceutical composition contains from about 20 to about 650 mg of excipient. In some embodiments, the pharmaceutical composition contains from about 20 to about 600 mg of excipient. In some embodiments, the pharmaceutical composition contains from about 20 to about 550 mg of excipient. In some embodiments, the pharmaceutical composition contains from about 20 to about 500 mg of excipient. In some embodiments, the pharmaceutical composition contains from about 20 to about 450 mg of excipient. In some embodiments, the pharmaceutical composition contains from about 20 to about 400 mg of excipient. In some embodiments, the pharmaceutical composition contains from about 20 to about 350 mg of excipient. In some embodiments, the pharmaceutical composition contains from about 20 to about 300 mg of excipient. In some embodiments, the pharmaceutical composition contains from about 20 to about 275 mg of excipient. In some embodiments, the pharmaceutical composition contains from about 20 to about 250 mg of excipient. In some embodiments, the pharmaceutical composition contains from about 20 to about 225 mg of excipient. In some embodiments, the pharmaceutical composition contains from about 20 to about 200 mg of excipient. In some embodiments, the pharmaceutical composition contains from about 25 to about 300 mg of excipient. In some embodiments, the pharmaceutical composition contains from about 25 to about 275 mg of excipient. In some embodiments, the pharmaceutical composition contains from about 25 to about 250 mg of excipient. In some embodiments, the pharmaceutical composition contains from about 25 to about 225 mg of excipient. In some embodiments, the pharmaceutical composition contains from about 25 to about 200 mg of excipient. In some embodiments, the filler is selected from lactose, mannitol, dicalcium phosphate, microcrystalline cellulose, siliconized microcrystalline cellulose, starch, and pregelatinized starch (1500 starch). In some embodiments, the pharmaceutical composition contains from about 30 to about 300 mg of excipient. In some embodiments, the pharmaceutical composition contains from about 30 to about 275 mg of excipient. In some embodiments, the pharmaceutical composition contains from about 30 to about 250 mg of excipient. In some embodiments, the pharmaceutical composition contains from about 30 to about 225 mg of excipient. In some embodiments, the pharmaceutical composition contains from about 30 to about 200 mg of excipient. In some embodiments, the pharmaceutical composition contains from about 30 to about 175 mg of excipient. In some embodiments, the pharmaceutical composition contains from about 30 to about 150 mg of excipient. In some embodiments, the pharmaceutical composition contains about 30 mg of excipient. In some embodiments, the pharmaceutical composition contains about 35 mg of excipient. In some embodiments, the pharmaceutical composition contains about 40 mg of excipient. In some embodiments, the pharmaceutical composition contains about 45 mg of excipient. In some embodiments, the pharmaceutical composition contains about 50 mg of excipient. In some embodiments, the pharmaceutical composition contains about 55 mg of excipient. In some embodiments, the pharmaceutical composition contains about 60 mg of excipient. In some embodiments, the pharmaceutical composition contains about 65 mg of excipient. In some embodiments, the pharmaceutical composition contains about 70 mg of excipient. According to

- 31 045280 In some embodiments, the pharmaceutical composition contains about 75 mg of excipient. In some embodiments, the pharmaceutical composition contains about 80 mg of excipient. In some embodiments, the pharmaceutical composition contains about 85 mg of excipient. In some embodiments, the pharmaceutical composition contains about 90 mg of excipient. In some embodiments, the pharmaceutical composition contains about 95 mg of excipient. In some embodiments, the pharmaceutical composition contains about 100 mg of excipient. In some embodiments, the pharmaceutical composition contains about 105 mg of excipient. In some embodiments, the pharmaceutical composition contains about 110 mg of excipient. In some embodiments, the pharmaceutical composition contains about 115 mg of excipient. In some embodiments, the pharmaceutical composition contains about 120 mg of excipient. In some embodiments, the pharmaceutical composition contains about 125 mg of excipient. In some embodiments, the pharmaceutical composition contains about 130 mg of excipient. In some embodiments, the pharmaceutical composition contains about 135 mg of excipient. In some embodiments, the pharmaceutical composition contains about 140 mg of excipient. In some embodiments, the pharmaceutical composition contains about 145 mg of excipient. In some embodiments, the pharmaceutical composition contains about 150 mg of excipient. In some embodiments, the pharmaceutical composition contains about 155 mg of excipient. In some embodiments, the pharmaceutical composition contains about 160 mg of excipient. In some embodiments, the pharmaceutical composition contains about 165 mg of excipient. In some embodiments, the pharmaceutical composition contains about 170 mg of excipient. In some embodiments, the pharmaceutical composition contains about 175 mg of excipient. In some embodiments, the pharmaceutical composition contains about 180 mg of excipient. In some embodiments, the pharmaceutical composition contains about 185 mg of excipient. In some embodiments, the pharmaceutical composition contains about 190 mg of excipient. In some embodiments, the pharmaceutical composition contains about 195 mg of excipient. In some embodiments, the pharmaceutical composition contains about 200 mg of excipient.

In some embodiments, the pharmaceutical composition contains a disintegrant. In some embodiments, the disintegrant is selected from corn starch, potato starch, microcrystalline cellulose, methylcellulose, croscarmellose sodium, sodium starch glycolate, povidone, crospovidone, hypromellose, hydroxypropylcellulose, polyvinyl alcohol, alginic acid, sodium alginate, agar, guar, locust bean, karaia , pectin, tragacanth, bentonite, citrus pulp and sodium lauryl sulfate.

In some embodiments, the disintegrant is selected from povidone, crospovidone, hypromellose, croscarmellose sodium, hydroxypropylcellulose, and polyvinyl alcohol. In some embodiments, the disintegrant is polyvinyl alcohol. In some embodiments, the disintegrant is hydroxypropylcellulose. In some embodiments, the leavening agent is hypromellose. In some embodiments, the disintegrant is povidone. In some embodiments, the disintegrant is crospovidone. In some embodiments, the leavening agent is croscarmellose sodium. In some embodiments, the pharmaceutical composition contains from about 3 to about 125 mg of disintegrant. In some embodiments, the pharmaceutical composition contains from about 3 to about 100 mg of disintegrant. In some embodiments, the pharmaceutical composition contains from about 3 to about 75 mg of disintegrant. In some embodiments, the pharmaceutical composition contains from about 3 to about 60 mg of disintegrant. In some embodiments, the pharmaceutical composition contains from about 3 to about 50 mg of disintegrant. In some embodiments, the pharmaceutical composition contains from about 4 to about 60 mg of disintegrant. In some embodiments, the pharmaceutical composition contains from about 4 to about 55 mg of disintegrant. In some embodiments, the pharmaceutical composition contains from about 4 to about 50 mg of disintegrant. In some embodiments, the pharmaceutical composition contains from about 5 to about 50 mg of disintegrant. In some embodiments, the pharmaceutical composition contains from about 5 to about 45 mg of disintegrant. In some embodiments, the pharmaceutical composition contains from about 5 to about 40 mg of disintegrant. In some embodiments, the pharmaceutical composition contains from about 5 to about 35 mg of disintegrant. In some embodiments, the pharmaceutical composition contains from about 5 to about 30 mg of disintegrant. In some embodiments, the pharmaceutical composition contains from about 6 to about 30 mg of disintegrant. In some embodiments, the pharmaceutical composition contains about 5 mg of disintegrant. In some embodiments, the pharmaceutical composition contains about 6 mg of disintegrant. In some embodiments, the pharmaceutical composition contains about 7 mg of disintegrant. According to some

- 32 045280 In other embodiments, the pharmaceutical composition contains about 8 mg of disintegrant. In some embodiments, the pharmaceutical composition contains about 9 mg of disintegrant. In some embodiments, the pharmaceutical composition contains about 10 mg of disintegrant. In some embodiments, the pharmaceutical composition contains about 12 mg of disintegrant. In some embodiments, the pharmaceutical composition contains about 15 mg of disintegrant. In some embodiments, the pharmaceutical composition contains about 20 mg of disintegrant. In some embodiments, the pharmaceutical composition contains about 25 mg of disintegrant. In some embodiments, the pharmaceutical composition contains about 30 mg of disintegrant. In some embodiments, the pharmaceutical composition contains about 35 mg of disintegrant. In some embodiments, the pharmaceutical composition contains about 40 mg of disintegrant. In some embodiments, the pharmaceutical composition contains from about 3 to about 150 mg of a disintegrant, wherein the disintegrant is crospovidone. In some embodiments, the pharmaceutical composition contains from about 3 to about 100 mg of a disintegrant, wherein the disintegrant is crospovidone. In some embodiments, the pharmaceutical composition contains from about 3 to about 75 mg of a disintegrant, wherein the disintegrant is crospovidone. In some embodiments, the pharmaceutical composition contains from about 3 to about 60 mg of a disintegrant, wherein the disintegrant is crospovidone. In some embodiments, the pharmaceutical composition contains from about 5 to about 50 mg of a disintegrant, wherein the disintegrant is crospovidone. In some embodiments, the pharmaceutical composition contains from about 5 to about 40 mg of a disintegrant, wherein the disintegrant is crospovidone. In some embodiments, the pharmaceutical composition contains from about 5 to about 35 mg of a disintegrant, wherein the disintegrant is crospovidone. In some embodiments, the pharmaceutical composition contains from about 5 to about 30 mg of a disintegrant, wherein the disintegrant is crospovidone. In some embodiments, the pharmaceutical composition contains from about 5 to about 30 mg of a disintegrant, wherein the disintegrant is crospovidone. In some embodiments, the pharmaceutical composition contains from about 3 to about 100 mg of a disintegrant, wherein the disintegrant is croscarmellose sodium. In some embodiments, the pharmaceutical composition contains from about 3 to about 75 mg of a disintegrant, wherein the disintegrant is croscarmellose sodium. In some embodiments, the pharmaceutical composition contains from about 3 to about 60 mg of a disintegrant, wherein the disintegrant is croscarmellose sodium. In some embodiments, the pharmaceutical composition contains from about 5 to about 50 mg of a disintegrant, wherein the disintegrant is croscarmellose sodium. In some embodiments, the pharmaceutical composition contains from about 5 to about 40 mg of a disintegrant, wherein the disintegrant is croscarmellose sodium. In some embodiments, the pharmaceutical composition contains from about 5 to about 35 mg of a disintegrant, wherein the disintegrant is croscarmellose sodium. In some embodiments, the pharmaceutical composition contains from about 5 to about 30 mg of a disintegrant, wherein the disintegrant is croscarmellose sodium. In some embodiments, the pharmaceutical composition contains from about 5 to about 30 mg of a disintegrant, wherein the disintegrant is croscarmellose sodium.

In some embodiments, the pharmaceutical composition further comprises a lubricant. In some embodiments, the lubricant is selected from magnesium stearate, stearic acid, and sodium stearyl fumarate. In some embodiments, the lubricant is stearic acid. In some embodiments, the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition contains from about 0.1 to about 8 mg of lubricant. In some embodiments, the pharmaceutical composition contains from about 0.1 to about 6 mg of lubricant. In some embodiments, the pharmaceutical composition contains from about 0.1 to about 5 mg of lubricant. In some embodiments, the pharmaceutical composition contains from about 0.1 to about 4 mg of lubricant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 10 mg of lubricant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 8 mg of lubricant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 7 mg of lubricant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 6 mg, in which embodiments the pharmaceutical composition contains from about 0.2 to about 5 mg of lubricant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 4 mg of lubricant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 3.5 mg of lubricant. In some embodiments, the pharmaceutical composition contains from about

- 33 045280

0.2 to about 3 mg lubricant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 2.5 mg of lubricant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 2 mg of lubricant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 1.5 mg of lubricant. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 3 mg of lubricant. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 2.5 mg of lubricant. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 2 mg of lubricant. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 1.5 mg of lubricant. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 1 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 0.1 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 0.15 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 0.2 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 0.25 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 0.3 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 0.35 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 0.4 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 0.45 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 0.5 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 0.6 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 0.7 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 0.8 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 0.9 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 1 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 1.1 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 1.2 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 1.3 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 1.4 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 1.5 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 1.6 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 1.7 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 1.8 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 1.9 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 2 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 2.5 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 3 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 4 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 5 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 6 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 7 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 8 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 9 mg of lubricant. In some embodiments, the pharmaceutical composition contains about 10 mg of lubricant. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 10 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 5 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 4 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 3 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 2.5 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 2 mg

- 34 045280 lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 1.5 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 1 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 4 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 3 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 2.5 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 2 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 1.5 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 1 mg of a lubricant, wherein the lubricant is sodium stearyl fumarate. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 10 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 5 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 4 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 3 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 2.5 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 2 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 1.5 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition contains from about 0.2 to about 1 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 4 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 3 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 2.5 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 2 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 1.5 mg of a lubricant, wherein the lubricant is magnesium stearate. In some embodiments, the pharmaceutical composition contains from about 0.3 to about 1 mg of a lubricant, wherein the lubricant is magnesium stearate.

In some embodiments, 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate is in free base form.

In some embodiments, the pharmaceutical composition contains from about 1 to about 60 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 55 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 50 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 45 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 40 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-35 free base 045280 (trifluoromethyl)benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 35 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 30 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 25 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 20 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 15 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 10 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 30 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 25 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 20 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 15 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 10 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) free base )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 1 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 1.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) free base benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 2 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 2.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl) free base benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 3 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 3.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) free base benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 4 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 4.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) free base benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 6 mg

- 36 045280 free base of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 7 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 8 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 9 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 10 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 11 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 12 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 13 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 14 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 15 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 16 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 17 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 18 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 19 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 20 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 25 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4(trifluoromethyl)benzyl)piperazine free base -1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 30 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 35 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 40 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 45 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 50 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

- 37 045280

In some embodiments, the pharmaceutical composition contains about 55 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 60 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) free base. piperazine-1-carboxylate.

In some embodiments, 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate is in a pharmaceutically acceptable form salt.

In some embodiments, 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate is the hydrochloride 1, 1,3,3,3hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 60 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl hydrochloride )piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 55 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl hydrochloride )piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 50 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl hydrochloride )piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 45 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl hydrochloride )piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 40 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl hydrochloride )piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 35 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl hydrochloride )piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 30 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl hydrochloride )piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 25 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl hydrochloride )piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 20 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl hydrochloride )piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 15 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl hydrochloride )piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 10 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl hydrochloride )piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 30 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl hydrochloride )piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 25 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl hydrochloride )piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 20 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl hydrochloride )piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 15 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl hydrochloride )piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 10 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl hydrochloride )piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 1 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride - 38 045280 carboxylate.

In some embodiments, the pharmaceutical composition contains about 1.5 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 2 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride carboxylate.

In some embodiments, the pharmaceutical composition contains about 2.5 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine hydrochloride -1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 3 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride carboxylate.

In some embodiments, the pharmaceutical composition contains about 3.5 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4(trifluoromethyl)benzyl)piperazin-hydrochloride 1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 4 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride carboxylate.

In some embodiments, the pharmaceutical composition contains about 4.5 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4(trifluoromethyl)benzyl)piperazin-hydrochloride 1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 5 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride carboxylate.

In some embodiments, the pharmaceutical composition contains about 6 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride carboxylate.

In some embodiments, the pharmaceutical composition contains about 7 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride carboxylate.

In some embodiments, the pharmaceutical composition contains about 8 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride carboxylate.

In some embodiments, the pharmaceutical composition contains about 9 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride carboxylate.

In some embodiments, the pharmaceutical composition contains about 10 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4(trifluoromethyl)benzyl)piperazine-1-hydrochloride carboxylate.

In some embodiments, the pharmaceutical composition contains about 11 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride -carboxylate.

In some embodiments, the pharmaceutical composition contains about 12 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride -carboxylate.

In some embodiments, the pharmaceutical composition contains about 13 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride -carboxylate.

In some embodiments, the pharmaceutical composition contains about 14 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride -carboxylate.

In some embodiments, the pharmaceutical composition contains about 15 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride -carboxylate.

In some embodiments, the pharmaceutical composition contains about 16 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride -carboxylate.

In some embodiments, the pharmaceutical composition contains about 17 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride -carboxylate.

In some embodiments, the pharmaceutical composition contains about 18 mg

- 39 045280 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate hydrochloride.

In some embodiments, the pharmaceutical composition contains about 19 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride -carboxylate.

In some embodiments, the pharmaceutical composition contains about 20 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride -carboxylate.

In some embodiments, the pharmaceutical composition contains about 25 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride -carboxylate.

In some embodiments, the pharmaceutical composition contains about 30 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride -carboxylate.

In some embodiments, the pharmaceutical composition contains about 35 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride -carboxylate.

In some embodiments, the pharmaceutical composition contains about 40 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride -carboxylate.

In some embodiments, the pharmaceutical composition contains about 45 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride -carboxylate.

In some embodiments, the pharmaceutical composition contains about 50 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride -carboxylate.

In some embodiments, the pharmaceutical composition contains about 55 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride -carboxylate.

In some embodiments, the pharmaceutical composition contains about 60 mg of 1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 hydrochloride -carboxylate.

In some embodiments, 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate is the fumarate 1, 1,1,3,3,3hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 60 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 55 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 50 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 45 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 40 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 35 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-( trifluoromethyl)benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 30 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 25 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 20 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

- 40 045280

In some embodiments, the pharmaceutical composition contains from about 1 to about 15 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 1 to about 10 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 30 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 25 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 20 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 15 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) fumarate )benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains from about 2 to about 10 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl) fumarate) benzyl)piperazine-1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 1 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate -1carboxylate.

In some embodiments, the pharmaceutical composition contains about 1.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl fumarate )piperazine 1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 2 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate -1carboxylate.

In some embodiments, the pharmaceutical composition contains about 2.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl fumarate )piperazine 1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 3 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate -1carboxylate.

In some embodiments, the pharmaceutical composition contains about 3.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl fumarate )piperazine 1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 4 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate -1carboxylate.

In some embodiments, the pharmaceutical composition contains about 4.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl fumarate )piperazine 1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 6 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 7 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 8 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 9 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 10 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine fumarate - 41 045280

1-carboxylate.

In some embodiments, the pharmaceutical composition contains about 11 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 12 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 13 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 14 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 15 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 16 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 17 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 18 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 19 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 20 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 25 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 30 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 35 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 40 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 45 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 50 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 55 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

In some embodiments, the pharmaceutical composition contains about 60 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine fumarate1 -carboxylate.

Synthesis of pharmaceutical compounds.

The pharmaceutical compositions described herein contain 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof and pharmaceutically acceptable excipients. In some embodiments, the pharmaceutical compositions described herein are manufactured by hot melt extrusion. In some embodiments, 1,1,1,3,3,3hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate or

- 42 045280 its pharmaceutically acceptable salt, polymeric carrier, surfactant and glidant were uniformly mixed and then extruded at elevated temperature to obtain an amorphous solid dispersion of 1,1,1,3,3,3-hexafluoropropan-2-yl- 4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof.

In some embodiments, 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate, or a pharmaceutically acceptable salt thereof , the polymer carrier, plasticizer, surfactant and glidant were uniformly mixed and then extruded at elevated temperature to obtain a solid amorphous dispersion of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2- (pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 carboxylate or a pharmaceutically acceptable salt thereof.

In some embodiments, 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate hydrochloride, polymeric carrier , surfactant, glidant and potassium dihydrogen phosphate were uniformly mixed and then extruded at elevated temperature to obtain a solid amorphous dispersion of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-( pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 carboxylate.

In some embodiments of the present invention, 1,1,1,3,3,3hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate hydrochloride, polymeric The carrier, plasticizer, surfactant, glidant and potassium dihydrogen phosphate were uniformly mixed and then extruded at elevated temperature to obtain a solid amorphous dispersion of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-( 2-(pyrrolidin-1-yl)-4(trifluoromethyl)benzyl)piperazine-1-carboxylate.

In some embodiments, an amorphous solid dispersion of 1,1,1,3,3,3hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate or pharmaceutically acceptable salt is mixed with the excipient, disintegrant and lubricant and compressed to form 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)4-(trifluoromethyl) tablets )benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof.

In some embodiments, the pharmaceutical composition contains from about 1 to about 60 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains from about 1 to about 55 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains from about 1 to about 50 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains from about 1 to about 45 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains from about 1 to about 40 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains from about 1 to about 35 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains from about 1 to about 30 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains from about 1 to about 25 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains from about 1 to about 20 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains from about 1 to about 15 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains from about 1 to about 10 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains from about 2 to about 30 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl) - 43 045280 piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains from about 2 to about 25 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains from about 2 to about 20 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains from about 2 to about 15 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains from about 2 to about 10 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains about 1 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains about 1.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) piperazine-1carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains about 2 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains about 2.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) piperazine-1carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains about 3 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine- 1 carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains about 3.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) piperazine-1carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains about 4 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains about 4.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) piperazine-1carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains about 5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains about 6 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains about 7 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains about 8 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains about 9 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains about 10 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains about 11 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains about 12 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains about 13 mg

- 44 045280

1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains about 14 mg

1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 carboxylate or a pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains about 15 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per tablet.

In some embodiments, the pharmaceutical composition contains from about 1 to about 60 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains from about 1 to about 55 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains from about 1 to about 50 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains from about 1 to about 45 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains from about 1 to about 40 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains from about 1 to about 35 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains from about 1 to about 30 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains from about 1 to about 25 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains from about 1 to about 20 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains from about 1 to about 15 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains from about 1 to about 10 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains from about 2 to about 30 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains from about 2 to about 25 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains from about 2 to about 20 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains from about 2 to about 15 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains from about 2 to about 10 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains about 1 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or a pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains about 1.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) piperazine-1carboxylate or a pharmaceutically acceptable salt thereof per capsule tablet.

- 45 045280

In some embodiments, the pharmaceutical composition contains about 2 mg

1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1 carboxylate or a pharmaceutically acceptable salt thereof per capsule tablet .

In some embodiments, the pharmaceutical composition contains about 2.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) piperazine-1 carboxylate or a pharmaceutically acceptable salt thereof per capsule tablet.

In some embodiments, the pharmaceutical composition contains about 3 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains about 3.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) piperazine-1 carboxylate or a pharmaceutically acceptable salt thereof per capsule tablet.

In some embodiments, the pharmaceutical composition contains about 4 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains about 4.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) piperazine-1 carboxylate or a pharmaceutically acceptable salt thereof per capsule tablet.

In some embodiments, the pharmaceutical composition contains about 5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains about 6 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains about 7 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains about 8 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains about 9 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains about 10 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains about 11 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains about 12 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains about 13 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains about 14 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains about 15 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per capsule-shaped tablet.

In some embodiments, the pharmaceutical composition contains from about 1 to about 60 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains from about 1 to about 55 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains from about 1 to about 50 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains from about 1 to about 45 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl) - 46 045280 piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains from about 1 to about 40 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains from about 1 to about 35 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains from about 1 to about 30 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains from about 1 to about 25 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains from about 1 to about 20 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains from about 1 to about 15 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains from about 1 to about 10 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains from about 2 to about 30 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains from about 2 to about 25 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains from about 2 to about 20 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains from about 2 to about 15 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains from about 2 to about 10 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl) benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains about 1 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains about 1.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) piperazine-1carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains about 2 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains about 2.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) piperazine-1carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains about 3 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine- 1 carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains about 3.5 mg of 11,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) piperazine-1carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains about 4 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains about 4.5 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl) piperazine-1carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains about 5 mg

- 47 045280

1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains about 6 mg

1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 carboxylate or a pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains about 7 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains about 8 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains about 9 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains about 10 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains about 11 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains about 12 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains about 13 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains about 14 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per capsule.

In some embodiments, the pharmaceutical composition contains about 15 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1 carboxylate or pharmaceutically acceptable salt thereof per capsule.

Excipients.

Suitable optional excipients for use in the pharmaceutical compositions described herein: 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl)benzyl) piperazine-1-carboxylate include any commonly used pharmaceutical excipients and are selected based on compatibility with the active pharmaceutical agent and the release profile properties of the desired dosage form. Excipients include, but are not limited to, binders, fillers, flow aids, disintegrants, lubricants, glidants, polymeric carriers, plasticizers, stabilizers, surfactants, and the like. A brief description of the excipients presented herein can be found, for example, in Remington: The Science and Practice of Pharmacy, Nineteenth Ed (Easton, Pa.: Mack Publishing Company, 1995); Hoover, John E., Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania 1975; Liberman, H.A. and Lachman, L., Eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, N.Y., 1980 and Pharmaceutical Dosage Forms and Drug Delivery Systems, Seventh Ed. (Lippincott Williams & Wilkins, 1999), which are incorporated herein by reference in their entirety.

Binders provide adhesive properties to solid oral dosage forms: for powder capsule formulations, they promote the formation of plugs that can fill soft or hard capsule shells, and for tablet formulations, they maintain the integrity of the tablet after compression and help ensure uniform mixing prior to the compression or filling stage . Materials suitable for use as binders in the solid dosage forms described herein include, but are not limited to, carboxymethylcellulose, methylcellulose (e.g., Methocel®), hydroxypropyl methylcellulose (e.g., Hypromellose USP Pharmacoat-603), hydroxypropyl methylcellulose acetate stearate ( Aqoate HS-LF and HS), hydroxyethylcellulose, hydroxypropylcellulose (e.g. Klucel®), ethylcellulose (e.g. Ethocel®) and microcrystalline cellulose (e.g. Avicel®), microcrystalline dextrose, amylose, magnesium aluminum silicate, polysaccharide acids, bentonites, gelatin, polyvinylpyrrolidone/vinyl acetate copolymer, crospovidone, povidone, starch, pregelatinized starch, tragacanth, dextrin, sugars such as sucrose (e.g. Dipac®), glucose, dextrose, molasses, mannitol, sorbitol, xylitol (e.g. Xylitab®), lactose, and natural or synthetic gums such as gum, tragacanth, gatti, isapol husk gum, starch, polyvinylpyrrolidone (for example, Povidone® CL, Kollidon® CL, Polyplasdone® XL-10 and Povidone® K-12 ), larch arabogalactan, Veegum®, polyethylene glycol, waxes, sodium alginate, etc. In some embodiments, the binder is hypromellose, hydroxypropylcellulose, or ethylcellulose. In some embodiments, the binder is hypromellose. In some embodiments, the binder is hydroxypropylcellulose. In some embodiments, the binder is ethylcellulose.

Excipients or diluents add volume to a pharmaceutical formulation. Such compounds include, for example, lactose; starch; mannitol; sorbitol; dextrose; microcrystalline cellulose such as Avicel®; dibasic calcium phosphate; aqueous dicalcium phosphate; tricalcium phosphate; calcium phosphate; anhydrous lactose; spray-dried lactose; pregelatinized starch; compressed sugar such as Di-Pac® (Amstar); hydroxypropyl methylcellulose; sucrose-based diluents; confectioner's sugar; monobasic calcium sulfate monohydrate; calcium sulfate dihydrate; calcium lactate trihydrate; dextrans; hydrolyzed cereal solids; amylose; powdered cellulose; calcium carbonate; glycine; kaolin; sodium chloride; inositol; bentonite, etc. In some embodiments of the pharmaceutical formulations described herein, the excipient is lactose, mannitol, or microcrystalline cellulose. In some embodiments, the filler is lactose. In some embodiments, the excipient is mannitol. In some embodiments, the filler is dicalcium phosphate. In some embodiments, the filler is microcrystalline cellulose. In some embodiments, the filler is siliconized microcrystalline cellulose. In some embodiments, the filler is starch. In some embodiments, the filler is pregelatinized starch (1500 starch).

Glidants improve the flow characteristics of powder mixtures. Such compounds include, for example, fumed silica such as Cab-o-sil®; tribasic calcium phosphate, talc, corn starch, DL-leucine, sodium lauryl sulfate, magnesium stearate, calcium stearate, sodium stearate, kaolin and micronized amorphous silica (Syloid®), etc. In some embodiments of the pharmaceutical compositions described herein, the glidant is colloidal silica or talc. In some embodiments, the glidant is talc. In some embodiments, the glidant is colloidal silica.

Lubricants are compounds that prevent, reduce or inhibit adhesion or friction of materials. Exemplary lubricants include, for example, stearic acid; calcium hydroxide, talc; a hydrocarbon such as mineral oil, or a hydrogenated vegetable oil such as hydrogenated soybean oil (Sterotex®), Lubritab®, Cutina®; higher fatty acids and their alkali and alkaline earth metal salts such as aluminum, calcium, magnesium, zinc, stearic acid, sodium stearates, magnesium stearate, glycerin, talc, waxes, Stearowet®, boric acid, sodium acetate, leucine, polyethylene glycol or methoxypolyethylene glycol , such as Carbowax™, sodium oleate, glyceryl behenate (Compitrol 888®), glyceryl palmitostearate (Precirol®), colloidal silica such as Syloid™, Carb-O-Sil®, starch such as corn starch, silicone oil, surfactant active substance, etc. Hydrophilic lubricants include, for example, sodium stearyl fumarate (currently sold under the trade name PRUV®), polyethylene glycol (PEG), magnesium lauryl sulfate, sodium lauryl sulfate (SLS), sodium benzoate, sodium chloride, and the like. In some embodiments of the pharmaceutical formulations described herein, the lubricant is magnesium stearate, stearic acid, or sodium stearyl fumarate. In some embodiments, the lubricant is stearic acid. In some embodiments, the lubricant is sodium stearyl fumarate. In some embodiments, the lubricant is magnesium stearate. Disintegrants facilitate the breakdown or disintegration of the pharmaceutical composition after administration. Examples of disintegrants include starch, for example, natural starch such as corn starch or potato starch, pregelatinized starch such as National 1551 or Amijel®, or sodium starch glycolate such as Promogel® or Explotab®; cellulose such as wood product, microcrystalline cellulose such as Avicel®, Avicel® PH101, Avicel® PH102, Avicel® PH105, Elcema® P100, Emcocel®, Vivacel®, Ming Tia® and Solka-Floc®, methylcellulose, croscarmellose or crosslinked cellulose such as cross-linked sodium carboxymethyl cellulose (Ac-Di-Sol®), cross-linked carboxymethyl cellulose or cross-linked croscarmellose; cross-linked starch such as sodium starch glycolate; a cross-linked polymer such as crospovidone; cross-linked polyvinylpyrrolidone; an alginate such as alginic acid

- 49 045280 slot, or an alginic acid salt such as sodium alginate; clay such as Veegum® HV (magnesium aluminum silicate); gum such as agar, guar, carob, karaya, pectin or tragacanth; sodium starch glycolate; bentonite; natural sponge; a resin such as a cation exchange resin; citrus pulp; sodium lauryl sulfate; sodium lauryl sulfate in combination with starch, etc. In some embodiments of the pharmaceutical formulations described herein, the disintegrant is povidone, crospovidone, hypromellose, hydroxypropylcellulose, or polyvinyl alcohol. In some embodiments, the disintegrant is polyvinyl alcohol. In some embodiments, the disintegrant is hydroxypropylcellulose. In some embodiments, the leavening agent is hypromellose. In some embodiments, the disintegrant is povidone. In some embodiments, the disintegrant is crospovidone.

Polymeric carriers include compounds such as polyvinylpyrrolidone, for example polyvinylpyrrolidone K12, polyvinylpyrrolidone K17, polyvinylpyrrolidone K25 or polyvinylpyrrolidone K30, polyvinylpyrrolidone vinyl acetate (PVPVA 64-AS, hydroxypropyl methylcellulose) and methyl methacrylate polymers (Eudragit polymers), etc. .

In some embodiments, the pharmaceutical compositions described herein include one or more pH adjusting agents or buffering agents. In some embodiments, the pharmaceutical composition contains a buffer selected from acetates, carbonates, phosphates, citrates, and glutamates. In some embodiments, the buffer is selected from potassium dihydrogen phosphate, sodium bicarbonate, magnesium carbonate, sodium citrate, sodium dihydrogen phosphate, dipotassium monohydrogen phosphate, and disodium monohydrogen phosphate. In some embodiments, buffers are included in an amount necessary to maintain the pH of the pharmaceutical composition within an acceptable range.

In some embodiments, a film coating is applied around the pharmaceutical composition. In some embodiments, a shell of 1,1,1,3,3,3hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate or a pharmaceutically acceptable compound thereof salt is an immediate release coating. In some embodiments, the immediate release casing comprises hydroxypropyl methylcellulose (HPMC) with or without a plasticizer, and with or without surfactants and defoamers (clear, pigmented, or colored). In some embodiments, a shell of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate or pharmaceutical thereof acceptable salt is an immediate-release coating with a moisture-retaining barrier. In some embodiments, the film coating is Opadry AMB II beige. In some embodiments, the immediate release moisture barrier casing comprises polyvinyl alcohol (PVA) with or without a plasticizer, with or without surfactants and defoamers (clear, pigmented, or colored). In some embodiments, the compositions are formulated into particles (eg, for administration as a capsule) and some or all of the particles are coated. In some embodiments, the compositions are formulated into particles (eg, for administration as a capsule) and some or all of the particles are microencapsulated. In some embodiments, the compositions are formulated into particles (eg, for administration as a capsule), and some or all of the particles are not microencapsulated or coated.

In some embodiments, the compositions described herein are delivered using a pulsatile release dosage form. A pulsatile release dosage form is capable of providing one or more pulses of immediate release at predetermined times after a controlled delay time or at specific locations. Many other types of controlled release systems are known to those skilled in the art and are suitable for use with the formulations described herein. Examples of such delivery systems include, for example, polymer-based systems such as polylactic and polyglycolic acid, polyanhydrides and polycaprolactone; porous matrices, systems based on non-polymers that are lipids, including sterols such as cholesterol, cholesterol esters and fatty acids, or neutral fats such as mono-, di- and triglycerides; hydrogel release systems; silastic systems; peptide-based systems; wax coatings, biodegradable dosage forms, compressed tablets using conventional binders, etc. See, for example, Liberman et al., Pharmaceutical Dosage Forms, 2 Ed., Vol. 1, p. 209-214 (1990); Singh et al., Encyclopedia of Pharmaceutical Technology, ^2nd Ed., p. 751-753 (2002); U.S. Patent Nos. 4,327,725, 4,624,848, 4,968,509, 5,461,140, 5,456,923, 5,516,527, 5,622,721, 5,686,105, 5,700,410, 5,977,175, 6,465,014, and 6,932,983, each of which is specifically incorporated by reference.

Stabilizers include compounds such as any antioxidants such as butylated hydroxytoluene (BHT), sodium ascorbate and tocopherol; buffers, acids, etc.

- 50 045280

Surfactants include compounds such as sodium lauryl sulfate, sorbitan monooleate, polyoxyethylene sorbitan monooleate, polysorbates, polaxomers, bile salts, glyceryl monostearate, ethylene oxide-propylene oxide copolymers such as Pluronic® (BASF), d-a-tocopheryl polyethylene glycol succinate (vitamin ETPGS) and t. P.

The above excipients are provided as examples only and are not intended to include all possible variations. Other suitable classes of excipients include colorants, granulating agents, preservatives, defoamers, plasticizers, and the like. In addition, many excipients may have more than one role or function or may be classified into more than one group; classifications are descriptive only and are not intended to limit any use of a particular excipient.

Dosage forms.

In some embodiments, the pharmaceutical compositions described herein are 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1-carboxylate are included in solid unit dosage form.

The term solid unit dosage form means a dosage form intended to be swallowed as a single unit that is selected from the group consisting of powder, tablet, bite disintegrating tablet, chewable tablet, capsular tablet, capsule, gelatin capsule, effervescent powder, rapidly disintegrating tablet anti-abuse tablet, modified-release tablet, modified-release capsular tablet, modified-release capsule, and powder-derived aqueous suspension. In some embodiments, the solid dosage unit form is a tablet. In some embodiments, the solid dosage unit form is a capsule-shaped tablet. In some embodiments, the solid dosage unit forms are selected from the group consisting of soft capsules or hard capsules of any size or shape. In some embodiments, the solid dosage unit forms are soft capsules of any size or shape. In some embodiments, the solid dosage unit forms are hard capsules of any size or shape. Suitable capsules include, but are not limited to, spherical or elliptical soft elastic gelatin capsules; hard capsules of starch, cellulose or gelatin, such as Capill®, etc. Suitable capsule sizes include capsule sizes 000, 00EL, 00, 0EL, 0, 1, 2, 3, 4, or 5. Self-emulsifying drug delivery systems (SEDDS), as well as self-microemulsifying drug delivery systems (SMEDDS) and self-nanoemulsifying drug delivery systems (SNEDDS) form fine oil-in-water dispersions (emulsion, microemulsion, and nanoemulsion, respectively) when diluted in aqueous media or upon contact with gastrointestinal fluids. In some embodiments, the pharmaceutical compositions described herein comprise a self-emulsifying drug delivery system. In some embodiments, the pharmaceutical compositions described herein comprise a self-microemulsifying drug delivery system. In some embodiments, the pharmaceutical compositions described herein comprise a self-nanoemulsifying drug delivery system.

Ways.

In some embodiments, the pharmaceutical compositions described herein are 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin- 1-carboxylate modulates MAGL activity. Contemplated methods, for example, include exposing said enzyme to a pharmaceutical composition described herein. The ability of the pharmaceutical compositions described herein to modulate or inhibit MAGL is assessed using procedures known in the art and/or described herein. According to another aspect of the present disclosure, methods are provided for treating a disease associated with MAGL expression or activity in a patient.

Also disclosed herein are methods of treating and/or preventing a disorder such as one or more of acute or chronic pain and neuropathy in a patient in need thereof. The disclosed methods involve administering a pharmaceutically effective amount of a pharmaceutical composition described herein.

In another embodiment, a method of treating pain in a patient is provided, comprising administering a therapeutically effective amount of a pharmaceutical composition described herein to a patient in need thereof to treat said pain. In another embodiment, there is provided a method of treating neuropathic pain in a patient, comprising administering a therapeutically effective amount of a pharmaceutical composition described herein to a patient in need thereof to treat said neuropathic pain. In another embodiment, there is provided a method of treating inflammatory pain in a patient, comprising administering a therapeutically effective amount of a pharmaceutical composition described herein to a patient in need thereof to treat said inflammatory pain. In another embodiment, a method of treating complex regional pain syndrome in a patient in need thereof is provided, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein. In another embodiment, there is provided a method of treating a disease or disorder in a patient, comprising administering to the patient in need thereof a therapeutically effective amount of a pharmaceutical composition described herein, wherein the disease or disorder is selected from the group consisting of epilepsy/seizure disorder, multiple sclerosis, neuromyelitis optica (NMO), Tourette's syndrome, Alzheimer's disease and abdominal pain associated with irritable bowel syndrome. In another embodiment, there is provided a method of treating epilepsy/seizure disorder in a patient, comprising administering to the patient in need thereof a therapeutically effective amount of a pharmaceutical composition described herein. In another embodiment, a method of treating multiple sclerosis in a patient is provided, comprising administering to the patient in need thereof a therapeutically effective amount of a pharmaceutical composition described herein. In another embodiment, there is provided a method of treating neuromyelitis optica (NMO) in a patient, comprising administering to the patient in need thereof a therapeutically effective amount of a pharmaceutical composition described herein. In another embodiment, a method of treating Tourette's syndrome in a patient is provided, comprising administering to the patient in need thereof a therapeutically effective amount of a pharmaceutical composition described herein. In another embodiment, a method of treating Alzheimer's disease in a patient is provided, comprising administering to the patient in need thereof a therapeutically effective amount of a pharmaceutical composition described herein. In another embodiment, there is provided a method of treating abdominal pain associated with irritable bowel syndrome in a patient, comprising administering to the patient in need thereof a therapeutically effective amount of a pharmaceutical composition described herein.

In another embodiment, a method is provided for the treatment of acute pain, inflammatory pain, cancer pain, pain caused by peripheral neuropathy, central pain, fibromyalgia, migraine, vaso-occlusive pain crises due to sickle cell disease, spasticity or pain associated with multiple sclerosis, functional chest pain, rheumatoid arthritis, osteoarthritis or functional dyspepsia in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In another embodiment, there is provided a method of treating acute pain in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In another embodiment, there is provided a method of treating inflammatory pain in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In another embodiment, a method of treating cancer pain in a patient in need thereof is provided, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In another embodiment, there is provided a method of treating pain caused by peripheral neuropathy in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In another embodiment, a method of treating central pain in a patient in need thereof is provided, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In another embodiment, a method of treating fibromyalgia in a patient in need thereof is provided, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In another embodiment, a method of treating migraine in a patient in need thereof is provided, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In another embodiment, there is provided a method of treating vaso-occlusive painful crises of sickle cell disease in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In another embodiment, there is provided a method of treating spasticity or pain associated with multiple sclerosis in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a pharmaceutical agent described herein.

- 52 045280 composition.

In another embodiment, there is provided a method of treating functional chest pain in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In another embodiment, a method of treating rheumatoid arthritis in a patient in need thereof is provided, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In another embodiment, a method of treating osteoarthritis in a patient in need thereof is provided, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In another embodiment, a method of treating functional dyspepsia in a patient in need thereof is provided, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In some embodiments, disclosed herein is a method of treating a chronic motor tic disorder in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein. In some embodiments, disclosed herein is a method of treating a chronic motor tic disorder in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In some embodiments, disclosed herein is a method of treating attention deficit hyperactivity disorder (ADHD) in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein. In some embodiments, disclosed herein is a method of treating obsessive-compulsive disorder (OCD) in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In another embodiment, a method of reducing ocular intraocular pressure (IOP) in a patient in need thereof is provided, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein. In another embodiment, a method of treating glaucoma in a patient in need thereof is provided, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In another embodiment, a method of treating atopic dermatitis in a patient in need thereof is provided, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In another embodiment, there is provided a method of treating itching in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein. In another embodiment, a method of treating Down syndrome in a patient in need thereof is provided, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In some embodiments, disclosed herein is a method of synergistically enhancing the activity of an opioid analgesic in a patient being treated with an opioid analgesic, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein. In some embodiments, disclosed herein is a method of reducing acute side effects associated with an opioid analgesic in a patient being treated with an opioid analgesic, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In another embodiment, a method of treating dystonia in a patient in need thereof is provided, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In some embodiments, disclosed herein is a method of treating amyotrophic lateral sclerosis (ALS) or ALS-related symptoms in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In some embodiments, disclosed herein is a method of treating agitation associated with autism in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In another embodiment, there is provided a method of treating sleep disturbance or bladder dysfunction associated with multiple sclerosis in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein. In some embodiments, disclosed herein is a method of treating Huntington's disease in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In some embodiments, disclosed herein is a method of treating Parkinson's disease in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In some embodiments, disclosed herein is a method of improving functional outcome following stroke in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein. In some embodiments, disclosed herein is a method of treating traumatic brain injury in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

In some embodiments, disclosed herein is a method of treating trigeminal neuralgia in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein. In some embodiments, disclosed herein is a method of treating glossopharyngeal neuralgia in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition described herein.

The disclosed pharmaceutical compositions are administered to patients (animals and humans) in need of such treatment in dosages that will provide optimal pharmaceutical effectiveness. It is understood that the dosage required for use in any particular application will vary from patient to patient, not only depending on the specific pharmaceutical formulation selected, but also the nature of the condition being treated, the age and condition of the patient, concomitant medications, or special diet, monitored by the patient and other factors, with the appropriate dosage ultimately remaining at the discretion of the treating physician.

Although preferred embodiments of the present invention have been shown and described herein, those skilled in the art will appreciate that such embodiments are presented by way of example only. Numerous variations, changes and substitutions will be made by those skilled in the art without departing from the present invention. It should be understood that various alternatives to the embodiments of the present invention described herein may be used in the practice of the present invention. It is intended that the following claims define the scope of the present invention and that methods and structures within the scope of these claims and their equivalents are thereby covered.

Examples

The following examples provide exemplary methods for preparing exemplary pharmaceutical formulations of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1 -carboxylate. These examples are provided for illustrative purposes only and are not intended to limit the scope of the claims set forth herein.

Example 1. Pharmaceutical composition.

G 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate hydrochloride; tablets, 10 mg HCl salt per tablet: ___________________

Component mg/unit % Hydrochloride 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1 carboxylate 10 3.33 Polyvinylpyrrolidone KZO (PVP KZO) 72.1 24.03 PEG-400 12.9 4.3 Polysorbate 80 (Tween 80) 2 0.67 Silica 2 0.67 Potassium dihydrogen phosphate 1 0.33 Microcrystalline cellulose 102 168.5 56.17 Crospovidone thirty 10 Sodium stearyl fumarate 1.5 0.5 Total: 300 100.00

- 54 045280

G 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate hydrochloride; tablets, 10 mg free base per tablet: _______

Component mg/unit % Hydrochloride 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1 carboxylate 10.72 ¹ 1.4 Polyvinylpyrrolidone KZO (PVP KZO) 76 10.1 PEG 400 8 1.07 Polysorbate 80 (Tween 80) 2 0.27 Silica 2 0.27 Potassium dihydrogen phosphate 2 0.27 Microcrystalline cellulose 102 608.8 81.17 Croscarmellose sodium 37.5 5.0 Sodium stearyl fumarate 3.75 0.5 Total: 750.00 100.00

40.72 mg of the drug substance 1,1,1,3,3,3-hexafluoropropan-2yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate hydrochloride stoichiometrically equivalent to 10.00 mg 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate as free grounds.

1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate hydrochloride, polyvinylpyrrolidone K30 (PVP K30), potassium dihydrogen phosphate, PEG-400 and polysorbate 80 (Tween 80) were mixed until a homogeneous mixture was obtained. The mixture was mixed with silica to obtain a free-flowing mixture. The mixture was extruded using a twin screw extruder. The extrudate was then crushed. The ground extrudate was mixed with microcrystalline cellulose 102, crospovidone or croscarmellose sodium and sodium stearyl fumarate to obtain a homogeneous tablet mixture. The tablet mixture was compressed into tablets.

Example 2. Pharmaceutical composition.

G 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate hydrochloride; tablets, 10 mg HC1 salt per tablet:

Component mg/unit % Hydrochloride 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1 carboxylate 10 3.33 Polyvinylpyrrolidone/vinyl acetate (PVPVA 64) 85 28.33 Polysorbate 80 (Tween 80) 2 0.67 Silica 2 0.67 Potassium dihydrogen phosphate 1 0.33 Microcrystalline cellulose 102 168.5 56.17 Crospovidone thirty 10 Sodium stearyl fumarate 1.5 0.5 Total: 300 100.00

1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate hydrochloride, polyvinylpyrrolidone/vinyl acetate ( PVPVA 64), potassium dihydrogen phosphate and polysorbate 80 (Tween 80) were mixed until a homogeneous mixture was obtained. The mixture was mixed with silica to obtain a free-flowing mixture. The mixture was extruded using a twin screw extruder. The extrudate was then crushed. The ground extrudate was mixed with microcrystalline cellulose 102, crospovidone and sodium stearyl fumarate to obtain a homogeneous tablet mixture. The tablet mixture was compressed into tablets.

Example 3. Pharmaceutical composition.

G 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate hydrochloride; capsules, 2, 10 and 50 mg (amount of free base per capsule):

-55045280

Ingredient Capsule 2 mg Capsule 10 mg Capsule 50 mg %(in May, relative) mg %(in May, relative) mg %(in May, relative) mg 1,1,1,3,3,3hexafluoropropan-2-yl-4-(2(pyrrolidin-1-yl)-4(trifluoromethyl)benzyl)piper zin-1-carboxylate hydrochloride 1.26 2.14 ¹ 6.31 10.72 ² 31.53 53.60 ³ Microcrystalline cellulose 91.74 155.9 6 86.69 147.38 61.47 104.5 Croscarmellose sodium 6.00 10.20 6.00 10.20 6.00 10.20 Magnesium stearate 1.00 1.70 1.00 1,700 1.00 1,700 Full filling 100.0 170.0 100.0 170.0 100.0 170.0

12.14 mg of the drug substance 1,1,1,3,3,3-hexafluoropropan-2yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate hydrochloride is stoichiometrically equivalent 2.00 mg 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate free base .

210.72 mg of the drug substance 1,1,1,3,3,3-hexafluoropropan-2yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate hydrochloride stoichiometrically equivalent 10.00 mg 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate free base .

353.60 mg of the drug substance 1,1,1,3,3,3-hexafluoropropan-2yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate hydrochloride stoichiometrically equivalent 50.00 mg 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate free base .

The following procedure was used to prepare 1,1,1,3,3,3hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate hydrochloride capsules:

1. Weigh enough capsules to fill the batch.

2. Weighing 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl)benzyl)piperazine-1-carboxylate hydrochloride, microcrystalline cellulose, croscarmellose sodium and magnesium stearate.

3. Sifting each of the following: hydrochloride, 1,1,3,3,3-hexafluoropropan-2-yl-4-(2(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate, microcrystalline cellulose and croscarmellose sodium.

4. Transfer of screened materials (1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate hydrochloride, microcrystalline cellulose and croscarmellose sodium) into a blender and mix the material for 15 minutes.

5. Sift the magnesium stearate and add it to the blender in step 4. Mix the material for 2 minutes.

6. Pour the mixture into each of the orange-red size 2 capsules and check that the capsules are closed.

Example 4. Pharmaceutical composition.

G 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1 -yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate hydrochloride; tablets, 2 mg free base per tablet:

-

Claims (7)

Component mg/unit % Hydrochloride 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1 carboxylate 2.14 ¹ 1, 43 Polyvinylpyrrolidone K30 (PVP K30) 15.06 10.04 PEG-400 1.60 1.07 Polysorbate 80 (Tween 80) 0.40 0.27 Silica 0.40 0.27 Potassium dihydrogen phosphate 0.40 0.27 Microcrystalline cellulose 121.70 81.13 Croscarmellose sodium 7.50 5.0 Sodium stearyl fumarate 0.75 0.50 Total: 150.00 100.00 Opadry AMB II beige 6.00 4.00 Total: 156.00 104.00 12.14 mg of the drug substance 1,1,1,3,3,3-hexafluoropropan-2-yl4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate hydrochloride is stoichiometrically equivalent 2.00 mg 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate free base . 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate hydrochloride, polyvinylpyrrolidone (PVP K30 ), PEG-400, potassium dihydrogen phosphate and polysorbate 80 (Tween 80) were mixed until a homogeneous mixture was obtained. The mixture was mixed with silica to obtain a free-flowing mixture. The mixture was extruded using a twin screw extruder. The extrudate was then crushed. The ground extrudate was mixed with microcrystalline cellulose 102, croscarmellose sodium and sodium stearyl fumarate to obtain a homogeneous tablet mixture. The tablet mixture was compressed into tablets. The tablets were coated with Opadry AMB II beige in a pan. CLAIM 1. Pharmaceutical composition in solid dosage form containing: (a) about 1 to about 60 mg 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl)benzyl)piperazine-1 -carboxylate or a pharmaceutically acceptable salt thereof; (b) from about 50 to about 175 mg microcrystalline cellulose; (c) about 6 to about 15 mg croscarmellose sodium; and (d) from about 0.5 to about 2.5 mg of magnesium stearate. 2. The pharmaceutical composition according to claim 1, in which 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin1-yl)-4-(trifluoromethyl)benzyl)piperazine-1 -carboxylate is a hydrochloride. 3. Pharmaceutical composition in solid dosage form containing: (a) about 2.1 mg 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl)benzyl)piperazine-1-hydrochloride carboxylate; (b) about 156 mg microcrystalline cellulose; (c) about 10 mg croscarmellose sodium; and (d) about 1.7 mg magnesium stearate. 4. Pharmaceutical composition in solid dosage form containing: (a) about 10.7 mg 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl)benzyl)piperazine-1-hydrochloride carboxylate; (b) about 147 mg microcrystalline cellulose; (c) about 10.2 mg croscarmellose sodium; and (d) about 1.7 mg magnesium stearate. 5. Pharmaceutical composition in solid dosage form, containing: (a) about 53.6 mg 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4(trifluoromethyl)benzyl)piperazine-1-hydrochloride carboxylate; (b) about 104 mg microcrystalline cellulose; (c) about 10 mg croscarmellose sodium; and (d) about 1.7 mg magnesium stearate. 6. The pharmaceutical composition according to claim 1, wherein the solid dosage form is a tablet. - 57 045280 7. The pharmaceutical composition according to claim 1, wherein the solid dosage form is a capsule. Eurasian Patent Organization, EAPO Russia, 109012, Moscow, Maly Cherkassky lane, 2