Oral liquid enzalutamide composition

Abstract

Oral liquid enzalutamide compositions are provided. Oral liquid pharmaceutical compositions comprising enzalutamide and therapeutic methods using same are described herein.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to Indian Patent Application No. 202111044703, filed on October 1, 2021, the entire contents of which are incorporated herein by reference.

[0002] Described herein are oral liquid pharmaceutical compositions comprising enzalutamide and therapeutic uses thereof. [Background technology]

[0003] Enzalutamide is a small molecule androgen receptor inhibitor. It has been shown to competitively inhibit androgen binding to the androgen receptor, resulting in the inhibition of the nuclear translocation of androgen receptors and their interaction with DNA. Enzalutamide is indicated for use in the treatment of patients with castration-resistant and metastatic castration-sensitive prostate cancer.

[0004] Oral solid compositions of enzalutamide have been approved for use. XTANDI® is available in film-coated tablet and liquid-filled soft gelatin capsule dosage forms. The tablets are available in 40 mg and 80 mg doses. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglyceride with butylated hydroxyanisole, butylated hydroxytoluene, gelatin, sorbitol sorbitan solution, glycerin, purified water, titanium dioxide, polyvinyl acetate, and black iron oxide as inactive ingredients. The recommended dose of XTANDI® is 160 mg once daily. Thus, patients should take four 40 mg capsules, four 40 mg tablets, or two 80 mg tablets daily as a single dose.

[0005] Oral liquid compositions of enzalutamide are disclosed in WO 2018 / 037310. However, the disclosed formulation contains large amounts of LABRASOL® and propylene glycol. LABRASOL® has been reported to have a bitter taste (see, e.g., Isabelle et.al, Advanced Drug Delivery Reviews 142;128-140 (2019)), and thus the compositions of WO 2018 / 037310 do not taste good.

[0006] Thus, a need remains for enzalutamide pharmaceutical compositions, particularly oral liquid enzalutamide compositions. Summary of the Invention [Means for solving the problem]

[0007] Provided herein is an oral liquid pharmaceutical enzalutamide composition comprising: (i) enzalutamide; (ii) optionally, an oil; (iii) a surfactant and / or solubilizer; (iv) a co-surfactant; (v) an antioxidant; (vi) optionally, a precipitation inhibitor; and (vii) optionally, water.

[0008] In one aspect, an oral liquid pharmaceutical composition of enzalutamide is provided, (i) about 2.5% to about 6% w / w of enzalutamide; (ii) optionally, from about 0.5% to about 25% w / w of an oil selected from one or more of vegetable oils, flavor oils, and essential oils; (iii) from about 5% to about 85% w / w of a surfactant and / or a solubilizer, one or both of the surfactant and solubilizer, the surfactant comprising one or more selected from tocopherol polyethylene glycol succinate surfactants, polyoxyethylene castor oil surfactants, polyoxyl hydrogenated castor oil surfactants, polyoxyl hydroxystearic acid surfactants, lauroyl polyoxylglyceride and lauroyl macrogoglyceride surfactants, stearoyl polyoxylglyceride and stearoyl macrogoglyceride surfactants, and polyoxyl stearate surfactants, and the solubilizer comprising one or more selected from polyethylene glycol caprylic / capric acid glyceride solubilizers, polyglyceryl oleate solubilizers, and polyoxyethylene sorbitan monooleate solubilizers; (iv) from about 5% to about 25% w / w of a co-surfactant selected from one or more of propylene glycol monolaurate type II surfactants, oleoyl polyoxyl-6-glyceride surfactants, linoleoyl macrogol glyceride and linoleoyl polyoxyl glyceride surfactants, lauroyl macrogol glyceride and lauroyl polyoxyl glyceride surfactants, glycerol monocaprylocaprate type I surfactants, and propylene glycol monocaprylate type II surfactants; (v) about 0.01% to about 1% w / w of an antioxidant comprising one or more selected from DL-methionine, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), arginine, cysteine, ascorbic palmitate, sodium metabisulfite, sodium thiosulfate, propyl gallate, gamma linolenic acid, ethylenediaminetetraacetic acid (EDTA), ascorbic acid, and alpha tocopherol; (vi) optionally, from about 0.5% to about 5% w / w of a precipitation inhibitor selected from one or more of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer solubilizers, polyoxyethylene polyoxypropylene glycol solubilizers, polyvinyl pyrrolidone solubilizers, vinyl pyrrolidone-vinyl acetate copolymer solubilizers, polyvinyl alcohol / polyethylene glycol graft copolymer solubilizers, hydroxypropyl methylcellulose solubilizers, and hypromellose acetate succinate solubilizers; and (vii) optionally containing water (e.g., about 1% to about 5% w / w water).

[0009] In another aspect, an oral liquid pharmaceutical composition of enzalutamide is provided, (i) about 2.5% to about 6% w / w of enzalutamide; (ii) optionally, from about 0.5% to about 25% w / w of an oil selected from one or more of vegetable oils, flavor oils, and essential oils; (iii) about 5% to about 65% w / w of a surfactant comprising one or more selected from tocopherol succinate polyethylene glycol surfactants, polyoxyethylene castor oil surfactants, polyoxyl hydrogenated castor oil surfactants, hydroxystearic acid polyoxyl surfactants, lauroyl polyoxyl glycerides and lauroyl macrogoglycerides surfactants, stearoyl polyoxyl glycerides and stearoyl macrogoglycerides surfactants, and stearate polyoxyl surfactants; (iv) from about 5% to about 30% w / w of a co-surfactant selected from one or more of propylene glycol monolaurate type II surfactants, oleoyl polyoxyl-6-glyceride surfactants, linoleoyl macrogol glyceride and linoleoyl polyoxyl glyceride surfactants, lauroyl macrogol glyceride and lauroyl polyoxyl glyceride surfactants, glycerol monocaprylocaprate type I surfactants, and propylene glycol monocaprylate type II surfactants; (v) about 0.01% to about 1% w / w of an antioxidant comprising one or more selected from DL-methionine, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), arginine, cysteine, ascorbic palmitate, sodium metabisulfite, sodium thiosulfate, propyl gallate, gamma linolenic acid, ethylenediaminetetraacetic acid (EDTA), ascorbic acid, and alpha tocopherol; (vi) optionally, from about 0.5% to about 5% w / w of a precipitation inhibitor selected from one or more of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer solubilizers, polyoxyethylene polyoxypropylene glycol solubilizers, polyvinyl pyrrolidone solubilizers, vinyl pyrrolidone-vinyl acetate copolymer solubilizers, polyvinyl alcohol / polyethylene glycol graft copolymer solubilizers, hydroxypropyl methylcellulose solubilizers, and hypromellose acetate succinate solubilizers; and (vii) optionally containing water (e.g., about 1% to about 5% w / w water).

[0010] In some embodiments, the composition comprises about 20 to about 45 mg of enzalutamide per mL of the composition. In some embodiments, the composition comprises about 160 mg of enzalutamide per 2.5 to 6.0 mL of the composition. In some embodiments, the composition comprises about 160 mg of enzalutamide per 6.0 mL of the composition. In some embodiments, the composition comprises 160 mg of enzalutamide per 6.0 mL of the composition. In some embodiments, the composition is palatable.

[0011] In some embodiments, the composition comprises an oil. When present, the composition may comprise from about 0.5% to about 20% w / w of an oil, optionally from about 0.5% to about 5% w / w of a flavor or essential oil and from about 3% to about 15% w / w of a vegetable oil. In some embodiments, the composition comprises a flavor oil selected from one or more of peppermint oil, licorice oil, butterscotch oil, and aniseed oil. In some embodiments, the composition comprises a vegetable oil selected from one or more of corn oil, linseed oil, and rapeseed oil.

[0012] In some embodiments, the composition includes a surfactant. In some embodiments, the composition includes about 5% to about 65% w / w of a surfactant, for example, about 5% to about 55% w / w of a surfactant, for example, the surfactant includes one or more selected from tocopherol succinate polyethylene glycol surfactant, polyoxyethylene castor oil surfactant, polyoxyl hydrogenated castor oil surfactant, hydroxystearic acid polyoxyl surfactant, lauroyl polyoxyl glyceride and lauroyl macrogoglyceride surfactant, stearoyl polyoxyl glyceride and stearoyl macrogoglyceride surfactant, and stearate polyoxyl surfactant. In any embodiment, the composition may include about 5% to about 50% w / w of a surfactant.

[0013] In some embodiments, the surfactant comprises a tocopherol succinate polyethylene glycol surfactant and a polyoxyethylene castor oil surfactant, optionally where the tocopherol succinate polyethylene glycol surfactant is Vitamin E TPGS and / or the polyoxyethylene castor oil surfactant is PEG35 castor oil.

[0014] In some embodiments, the composition includes or further includes a solubilizer. In some embodiments, the composition includes about 10% to about 65% w / w solubilizer, for example, the solubilizer includes one or more selected from polyethylene glycol caprylic / capric glyceride solubilizer, polyglyceryl oleate solubilizer, and polyoxyethylene sorbitan monooleate solubilizer. In some embodiments, the solubilizer includes polyethylene glycol caprylic / capric glyceride solubilizer. In some embodiments, the solubilizer is ACCONON® MC8-2.

[0015] In any embodiment, the composition may comprise from about 5% to about 30% w / w, or from about 5% to about 25% w / w, or from about 5% to about 20% w / w of a co-surfactant. In some embodiments, the co-surfactant comprises a propylene glycol monolaurate type II surfactant, an oleoyl polyoxyl-6-glyceride surfactant, a glycerol monocaprylocaprate type I surfactant, or a propylene glycol monocaprylate type II surfactant, optionally, the propylene glycol monolaurate type II surfactant is CAPMUL® PG-12, the oleoyl polyoxyl-6-glyceride surfactant is LABRAFIL® M 1944 CS, the glycerol monocaprylocaprate type I surfactant is CAPMUL® MCM, and / or the propylene glycol monocaprylate type II surfactant is CAPMUL® PG-8.

[0016] In some embodiments, the antioxidant comprises one or more selected from DL-methionine, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), arginine, cysteine, ascorbic palmitate, sodium metabisulfite, sodium thiosulfate, propyl gallate, gamma linolenic acid, ethylenediaminetetraacetic acid (EDTA), ascorbic acid, and alpha tocopherol. In some embodiments, the antioxidant comprises one or more selected from DL-methionine, BHA, and BHT. In some embodiments, the antioxidant comprises DL-methionine. In some embodiments, the composition comprises about 0.05% to about 1% w / w antioxidant.

[0017] In some embodiments, the composition includes a precipitation inhibitor. When present, the composition may include about 0.5% to about 1% w / w of the precipitation inhibitor. The precipitation inhibitor may include a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer solubilizer, and optionally the precipitation inhibitor is SOLUPLUS®. In some embodiments, the composition includes an oil and a precipitation inhibitor.

[0018] In some embodiments, the composition further comprises about 10% to about 35% w / w of a co-solvent, the co-solvent comprising one or more selected from diethylene glycol monoethyl ether, glycofurol, and N-methylpyrrolidone, hi some embodiments, the co-solvent is a diethylene glycol monoethyl ether co-solvent.

[0019] In some embodiments, the composition further comprises one or more of a sweetener and a flavoring agent. In some embodiments, the sweetener comprises one or more selected from sucralose, ammonium glycyrrhizinate, saccharin, aspartame, potassium acesulfame, cyclamate, erythritol, and neotame, and the flavoring comprises one or more selected from vanilla flavor, banana flavor, grapefruit flavor, strawberry flavor, raspberry flavor, bubblegum flavor, and caramel flavor. In some embodiments, the sweetener comprises one or more selected from sucralose and ammonium glycyrrhizinate, and the flavoring comprises one or more selected from vanilla flavor and banana flavor.

[0020] In some embodiments, the composition comprises peppermint oil as the flavor oil and corn oil as the vegetable oil; the surfactant is present and is a tocopherol succinate polyethylene glycol surfactant; the co-surfactant is a propylene glycol monolaurate type II co-surfactant, the solubilizer is present and is a polyethylene glycol caprylic / capric glyceride solubilizer, the precipitation retardant is present and is a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant, and water is present.

[0021] In some embodiments, the composition comprises peppermint oil as the flavor oil and corn oil as the vegetable oil; the surfactant is a tocopherol polyethylene glycol succinate surfactant or a combination of a tocopherol polyethylene glycol succinate surfactant and a polyoxyethylene castor oil surfactant, optionally the surfactant is vitamin E TPGS or vitamin E TPGS and PEG35 castor oil; the co-surfactant is a propylene glycol monolaurate Type II co-surfactant, an oleoyl polyoxyl-6-glyceride co-surfactant, a glycerol monocaprylocaprate Type I co-surfactant, or a propylene glycol monocaprylate Type II co-surfactant; the precipitation inhibitor is present and is a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor.

[0022] In some embodiments, the composition comprises: (i) about 2.5% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 10% w / w vegetable oil; (iv) about 7% w / w of propylene glycol monolaurate type II cosurfactant; (v) about 15% w / w of a tocopherol succinate polyethylene glycol surfactant; (vi) about 60% w / w polyethylene glycol caprylic / capric glyceride solubilizer; (vii) about 0.5% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) antioxidants; (ix) optionally a sweetening agent; (x) optionally, a flavoring agent; and (xi) Contains water in an amount of about 1.5% w / w.

[0023] In the above specific embodiment, the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monolaurate type II co-surfactant is CAPMUL® PG-12; the tocopherol succinate polyethylene glycol surfactant is D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; and the antioxidant comprises one or more selected from DL methionine, BHA, and BHT. In further specific embodiments, the sweetener is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring is present and comprises vanilla and banana.

[0024] In some embodiments, the composition comprises: (i) about 2.5% w / w enzalutamide; (i) about 2.5% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 10% w / w vegetable oil; (iv) about 7% w / w of propylene glycol monolaurate type II cosurfactant; (v) about 15% w / w of a tocopherol succinate polyethylene glycol surfactant; (vi) about 60% w / w polyethylene glycol caprylic / capric glyceride solubilizer; (vii) about 0.5% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) antioxidants; (ix) optionally a sweetening agent; (x) optionally, a flavoring agent; and (xi) Contains water in an amount of about 3% w / w.

[0025] In certain of the foregoing embodiments, the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monolaurate type II co-surfactant is CAPMUL® PG-12; the tocopherol succinate polyethylene glycol surfactant is D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; and the antioxidant comprises DL-methionine. In further particular embodiments, the sweetener is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla and banana.

[0026] In some embodiments, the composition comprises: (i) about 2.5% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 10% w / w vegetable oil; (iv) about 7% w / w of propylene glycol monolaurate type II cosurfactant; (v) about 15% w / w of a tocopherol succinate polyethylene glycol surfactant; (vi) about 60% w / w polyethylene glycol caprylic / capric glyceride solubilizer; (vii) about 0.5% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) antioxidants; (ix) optionally a sweetening agent; (x) optionally, a flavoring agent; and (xi) Contains water in an amount of about 1.5% w / w.

[0027] In certain of the foregoing embodiments, the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monolaurate type II co-surfactant is CAPMUL® PG-12; the tocopherol succinate polyethylene glycol surfactant is D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; and the antioxidant comprises DL-methionine. In further particular embodiments, the sweetener is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla and banana.

[0028] In some embodiments, the composition comprises: (i) about 2.5% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 10% w / w vegetable oil; (iv) about 7% w / w of propylene glycol monolaurate type II cosurfactant; (v) about 15% w / w of a tocopherol succinate polyethylene glycol surfactant; (vi) about 60% w / w polyethylene glycol caprylic / capric glyceride solubilizer; (vii) antioxidants; (viii) optionally a sweetening agent; (ix) optionally, a flavoring agent; and (x) Contains water in an amount of about 3% w / w.

[0029] In certain of the foregoing embodiments, the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monolaurate type II co-surfactant is CAPMUL® PG-12; the tocopherol succinate polyethylene glycol surfactant is D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; and the antioxidant comprises DL-methionine. In further particular embodiments, the sweetener is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla and banana.

[0030] In some embodiments, the composition comprises: (i) about 2.5% w / w enzalutamide; (ii) about 7% w / w of propylene glycol monolaurate type II co-surfactant; (iii) about 15% w / w of a tocopherol succinate polyethylene glycol surfactant; (iv) about 60% w / w polyethylene glycol caprylic / capric glyceride solubilizer; (v) about 0.5% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (vi) antioxidants; (vii) optionally a sweetening agent; (viii) optionally, a flavoring agent; and (ix) Contains water in an amount of about 3% w / w.

[0031] In certain of the foregoing embodiments, the propylene glycol monolaurate type II co-surfactant is CAPMUL® PG-12; the tocopherol succinate polyethylene glycol surfactant is D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; and the antioxidant comprises DL methionine. In further particular embodiments, the sweetener is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla and banana.

[0032] In some embodiments, the composition comprises: (i) about 2.5% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 10% w / w vegetable oil; (iv) about 7% w / w of propylene glycol monolaurate type II cosurfactant; (v) about 15% w / w of a tocopherol succinate polyethylene glycol surfactant; (vi) about 60% w / w polyethylene glycol caprylic / capric glyceride solubilizer; (vii) about 0.5% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) antioxidants; (ix) optionally a sweetening agent; (x) optionally, a flavoring agent; and (xi) Contains water in an amount of about 3% w / w.

[0033] In certain of the foregoing embodiments, the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monolaurate type II co-surfactant is CAPMUL® PG-12; the tocopherol succinate polyethylene glycol surfactant is D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; and the antioxidant comprises arginine or cysteine. In further particular embodiments, the sweetener is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate, and the flavoring is present and comprises vanilla and banana.

[0034] In some embodiments, the composition comprises: (i) about 2.5% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 10% w / w vegetable oil; (iv) about 7% w / w of propylene glycol monolaurate type II cosurfactant; (v) about 15% w / w of a tocopherol succinate polyethylene glycol surfactant; (vi) about 60% w / w polyethylene glycol caprylic / capric glyceride solubilizer; (vii) about 0.5% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) antioxidants; (ix) optionally a sweetening agent; (x) optionally, a flavoring agent; and (xi) Contains water in an amount of about 1.5% w / w.

[0035] In certain of the foregoing embodiments, the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monolaurate type II co-surfactant is CAPMUL® PG-12; the tocopherol succinate polyethylene glycol surfactant is D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; and the antioxidant comprises DL-methionine. In further particular embodiments, the sweetener is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla and banana.

[0036] In some embodiments, the composition comprises: (i) about 3% w / w enzalutamide; (ii) about 1.0% w / w of flavor oil; (iii) about 3.5% w / w vegetable oil; (iv) about 13% w / w of an oleoyl polyoxyl-6-glyceride co-surfactant; (v) about 12% w / w of a tocopherol succinate polyethylene glycol surfactant; (vi) about 20% w / w diethylene glycol monoethyl ether co-solvent; (vii) about 26% w / w polyethylene glycol caprylic / capric glyceride solubilizer; (viii) about 0.75% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (ix) about 21% w / w polyoxyethylene castor oil surfactant; (x) antioxidants; (xi) optionally a sweetening agent; and (xii) optionally comprising a flavoring agent.

[0037] In certain of the foregoing embodiments, the flavor oil is peppermint oil; the vegetable oil is corn oil; the oleoyl polyoxyl-6-glyceride co-surfactant is LABRAFIL® M 1944 CS; the tocopherol succinate polyethylene glycol surfactant is Vitamin E TPGS; the diethylene glycol monoethyl ether co-solvent is TRANSCUTOL® HP; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; the polyoxyethylene castor oil surfactant is KOLLIPHOR® ELP; the antioxidant comprises one or more selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT); the sweetening agent is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla.

[0038] In some embodiments, the composition comprises: (i) about 4% w / w of enzalutamide; (ii) about 1.5% w / w of flavor oil; (iii) about 5% w / w vegetable oil; (iv) about 17% w / w of an oleoyl polyoxyl-6-glyceride co-surfactant; (v) about 6% w / w of a tocopherol succinate polyethylene glycol surfactant; (vi) about 25% w / w diethylene glycol monoethyl ether co-solvent; (vii) about 40% w / w polyethylene glycol caprylic / capric glyceride solubilizer; (viii) about 0.5% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (ix) antioxidants; (x) optionally a sweetening agent; and (xi) optionally containing a flavoring agent.

[0039] In certain of the foregoing embodiments, the flavor oil is peppermint oil; the vegetable oil is corn oil; the oleoyl polyoxyl-6-glyceride co-surfactant is LABRAFIL® M 1944 CS; the tocopherol succinate polyethylene glycol surfactant is D-α-tocopherol polyethylene glycol 1000 succinic acid surfactant; the diethylene glycol monoethyl ether co-solvent is TRANSCUTOL® HP; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; the antioxidant comprises one or more selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT); the sweetening agent is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla.

[0040] In some embodiments, the composition comprises: (i) about 3% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 12% w / w vegetable oil; (iv) about 13% w / w of an oleoyl polyoxyl-6-glyceride co-surfactant; (v) about 18% w / w of a tocopherol succinate polyethylene glycol surfactant; (vi) about 20% w / w diethylene glycol monoethyl ether co-solvent; (vii) about 0.75% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) about 30% w / w polyoxyethylene castor oil surfactant; (ix) antioxidants; (x) optionally a sweetening agent; and (xi) optionally containing a flavoring agent.

[0041] In certain of the foregoing embodiments, the flavor oil is peppermint oil; the vegetable oil is corn oil; the oleoyl polyoxyl-6-glyceride co-surfactant is LABRAFIL® M 1944 CS; the tocopherol succinate polyethylene glycol surfactant is Vitamin E TPGS; the diethylene glycol monoethyl ether cosolvent is TRANSCUTOL® HP; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; the polyoxyethylene castor oil surfactant is KOLLIPHOR® ELP; the antioxidant comprises one or more selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT); the sweetener is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla.

[0042] In some embodiments, the composition comprises: (i) about 3% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 11% w / w vegetable oil; (iv) about 7% w / w of glycerol monocaprylocaprate type I co-surfactant; (v) about 17% w / w of a tocopherol succinate polyethylene glycol surfactant; (vi) about 55% w / w polyethylene glycol caprylic / capric glyceride solubilizer; (vii) about 0.5% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) antioxidants; (ix) optionally a sweetening agent; and (x) optionally, flavoring agents.

[0043] In certain of the foregoing embodiments, the flavor oil is peppermint oil; the vegetable oil is corn oil; the glycerol monocaprylocaprate Type I co-surfactant is CAPMUL MCM; the tocopherol succinate polyethylene glycol surfactant is D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS; the antioxidant comprises one or more selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT); the sweetener is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla.

[0044] In some embodiments, the composition comprises: (i) about 3% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 11% w / w vegetable oil; (iv) about 7% w / w of propylene glycol monocaprylate type II co-surfactant; (v) about 17% w / w of a tocopherol succinate polyethylene glycol surfactant; (vi) about 55% w / w polyethylene glycol caprylic / capric glyceride solubilizer; (vii) about 0.5% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) antioxidants; (ix) optionally a sweetening agent; and (x) optionally, flavoring agents.

[0045] In certain of the foregoing embodiments, the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monocaprylate type II co-surfactant is CAPMUL® PG-8; the tocopherol succinate polyethylene glycol surfactant is D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; the antioxidant comprises one or more selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT); the sweetener is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla.

[0046] In some embodiments, the composition comprises: (i) about 3% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 11% w / w vegetable oil; (iv) about 7% w / w of propylene glycol monolaurate type II cosurfactant; (v) about 17% w / w of a tocopherol succinate polyethylene glycol surfactant; (vi) about 55% w / w polyethylene glycol caprylic / capric glyceride solubilizer; (vii) about 0.5% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) antioxidants; (ix) optionally a sweetening agent; and (x) optionally, flavoring agents.

[0047] In certain of the foregoing embodiments, the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monolaurate type II co-surfactant is CAPMUL® PG-12; the tocopherol succinate polyethylene glycol surfactant is D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; the antioxidant comprises one or more selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT); the sweetener is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla.

[0048] In some embodiments, the composition comprises: (i) about 3% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 12% w / w vegetable oil; (iv) about 15% w / w of an oleoyl polyoxyl-6-glyceride co-surfactant; (v) about 17% w / w of a tocopherol succinate polyethylene glycol surfactant; (vi) about 19% w / w diethylene glycol monoethyl ether co-solvent; (vii) about 0.75% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) about 28% w / w polyoxyethylene castor oil surfactant; (ix) antioxidants; (x) optionally a sweetening agent; and (xi) optionally containing a flavoring agent.

[0049] In certain of the foregoing embodiments, the flavor oil is peppermint oil; the vegetable oil is corn oil; the oleoyl polyoxyl-6-glyceride co-surfactant is LABRAFIL® M 1944 CS; the tocopherol succinate polyethylene glycol surfactant is Vitamin E TPGS; the diethylene glycol monoethyl ether cosolvent is TRANSCUTOL® HP; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; the polyoxyethylene castor oil surfactant is KOLLIPHOR® ELP; the antioxidant comprises one or more selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT); the sweetener is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla.

[0050] In some embodiments, the composition comprises: (i) about 3% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 10% w / w vegetable oil; (iv) about 7% w / w of propylene glycol monolaurate type II cosurfactant; (v) about 15% w / w of a tocopherol succinate polyethylene glycol surfactant; (vi) about 60% w / w polyethylene glycol caprylic / capric glyceride solubilizer; (vii) about 0.5% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) antioxidants; (ix) optionally a sweetening agent; and (x) optionally, flavoring agents.

[0051] In certain of the foregoing embodiments, the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monolaurate type II co-surfactant is CAPMUL® PG-12; the tocopherol succinate polyethylene glycol surfactant is D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; the antioxidant comprises one or more selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT); the sweetener is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla.

[0052] Also provided is an oral liquid pharmaceutical composition of enzalutamide, (i) about 160 mg of enzalutamide in a volume of about 3.5 mL to about 6.0 mL; (ii) about 0.5% to about 25% w / w of an oil selected from one or more of vegetable oils, flavor oils, and essential oils; (iii) about 5% to about 55% w / w of a surfactant comprising one or more selected from tocopherol succinate polyethylene glycol surfactants, polyoxyethylene castor oil surfactants, polyoxyl hydrogenated castor oil surfactants, hydroxystearic acid polyoxyl surfactants, lauroyl polyoxyl glycerides and lauroyl macrogoglycerides surfactants, stearoyl polyoxyl glycerides and stearoyl macrogoglycerides surfactants, and stearate polyoxyl surfactants; (iv) from about 5% to about 30% w / w of a co-surfactant selected from one or more of oleoyl polyoxyl-6-glyceride surfactants, linoleoyl macrogol glyceride and linoleoyl polyoxyl glyceride surfactants, lauroyl macrogol glyceride and lauroyl polyoxyl glyceride surfactants, glycerol monocaprylocaprate type I surfactants, propylene glycol monocaprylate type II surfactants, and propylene glycol monolaurate type II surfactants; and (v) about 0.5% to about 5% w / w of a precipitation inhibitor selected from one or more of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer solubilizer, a polyoxyethylene polyoxypropylene glycol solubilizer, a polyvinyl pyrrolidone solubilizer, a vinyl pyrrolidone-vinyl acetate copolymer solubilizer, a polyvinyl alcohol / polyethylene glycol graft copolymer solubilizer, a hydroxypropyl methylcellulose solubilizer, and a hypromellose acetate succinate solubilizer.

[0053] Also provided is an oral liquid pharmaceutical composition of enzalutamide, (i) about 3% to about 6% w / w of enzalutamide; (ii) about 0.5% to about 25% w / w of an oil selected from one or more of vegetable oils, flavor oils, and essential oils; (iii) about 5% to about 55% w / w of a surfactant comprising one or more selected from tocopherol succinate polyethylene glycol surfactants, polyoxyethylene castor oil surfactants, polyoxyl hydrogenated castor oil surfactants, hydroxystearic acid polyoxyl surfactants, lauroyl polyoxyl glycerides and lauroyl macrogoglycerides surfactants, stearoyl polyoxyl glycerides and stearoyl macrogoglycerides surfactants, and stearate polyoxyl surfactants; (iv) from about 5% to about 25% w / w of a co-surfactant selected from one or more of oleoyl polyoxyl-6-glyceride surfactants, linoleoyl macrogol glyceride and linoleoyl polyoxyl glyceride surfactants, lauroyl macrogol glyceride and lauroyl polyoxyl glyceride surfactants, glycerol monocaprylocaprate type I surfactants, propylene glycol monocaprylate type II surfactants, and propylene glycol monolaurate type II surfactants; and (v) about 0.5% to about 5% w / w of a precipitation inhibitor selected from one or more of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer solubilizer, a polyoxyethylene polyoxypropylene glycol solubilizer, a polyvinyl pyrrolidone solubilizer, a vinyl pyrrolidone-vinyl acetate copolymer solubilizer, a polyvinyl alcohol / polyethylene glycol graft copolymer solubilizer, a hydroxypropyl methylcellulose solubilizer, and a hypromellose acetate succinate solubilizer.

[0054] In some embodiments, the composition is packaged as a unit dose containing 160 mg of enzalutamide. In some embodiments, the unit dose has a volume of about 3.5 mL to about 6.0 mL.

[0055] In some embodiments, the composition does not include a caprylocaproyl polyoxyl-8 glyceride surfactant / solubilizer, and optionally the excluded caprylocaproyl polyoxyl-8 glyceride surfactant / solubilizer is one or both of LABRASOL® and LABRASOL® ALF. The embodiments excluding the caprylocaproyl polyoxyl-8 glyceride surfactant / solubilizer may still (optionally) include a polyethylene glycol caprylic / capric glyceride solubilizer (e.g., ACCONON® MC8 2, a polyethylene glycol caprylic / capric glyceride solubilizer).

[0056] In some embodiments, the composition does not include polyethylene glycol, and optionally, the excluded polyethylene glycol is polyethylene glycol 300 (PEG300) and / or polyethylene glycol 400 (PEG400). In some embodiments, the composition does not include propylene glycol. In some embodiments, the composition does not include ethanol.

[0057] Also provided herein are methods of administering enzalutamide to a subject in need thereof, comprising orally administering any of the compositions described herein.

[0058] Also provided is a method of treating prostate cancer comprising orally administering any of the compositions described herein to a subject in need thereof.

[0059] Also provided herein is an oral liquid pharmaceutical composition, as described herein, for use in treating prostate cancer.

[0060] Also provided herein is the use of enzalutamide in the preparation of a medicament for treating prostate cancer, wherein the medicament comprises an oral liquid pharmaceutical composition as described herein. [Brief description of the drawings]

[0061] [Figure 1] The dissolution profiles of Formulations 1 and 2 described in Table 1 and XTANDI® Capsule as a reference composition are shown. [Diagram 2] The dissolution profiles of Formulations 3, 4, 5 and 6 described in Table 1, and XTANDI® capsule as a reference composition are shown. [Diagram 3] The dissolution profiles of Formulations 7, 8 and 9 described in Table 2, and XTANDI® capsules as a reference composition are shown. [Figure 4]1 shows the mean plasma concentration-time profiles following administration of Formulations 1 and 2 or XTANDI® capsules as described in Table 1 to male beagle dogs. [Diagram 5] 1 shows the mean plasma concentration-time profiles following administration of Formulations 7, 8, and 9 or XTANDI® capsules as described in Table 2 to male beagle dogs. [Figure 6] The dissolution profiles of Formulations 1, 2, 3 and 4 described in Table 1, and XTANDI® capsule as a reference composition are shown. [Figure 7] 1 shows the dissolution profiles of Formulations 5, 6, 7, 8, and 9 described in Tables 1 and 2, as well as XTANDI® capsules as a reference composition. [Figure 8] The dissolution profiles of Formulations 10, 11, 12, 13, and 14 described in Table 3, as well as XTANDI® capsules as a reference composition, are shown. [Figure 9] 4 shows the dissolution profiles of Formulations 15, 16, and 17 described in Table 4, as well as XTANDI® capsules as a reference composition. [Figure 10] The dissolution profiles of Formulations 10, 11, 12, 13, and 14 described in Table 3, as well as XTANDI® capsules as a reference composition, are shown. [Figure 11] 4 shows the dissolution profiles of Formulations 15, 16, and 17 described in Table 4, as well as XTANDI® capsules as a reference composition. [Figure 12] 1 shows the mean plasma concentration-time profiles following administration of Formulation 10 or XTANDI® capsules to human subjects. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0062] The present disclosure provides an oral liquid pharmaceutical composition of enzalutamide that provides a therapeutically effective dose of enzalutamide in a convenient volume composition. The compositions described herein are generally palatable. Thus, the compositions described herein may promote patient compliance and adherence to treatment. In addition, the compositions described herein reduce the tablet burden of enzalutamide therapy, which may be particularly important for target patient populations, including elderly patients and patients with dysphagia, who may have difficulty swallowing. As described in more detail below, the composition may include (i) enzalutamide; (ii) optionally, an oil selected from one or more of vegetable oils, flavor oils, and essential oils; (iii) a surfactant and / or solubilizer, (iv) a co-surfactant, (v) an antioxidant, (vi) optionally, a precipitation inhibitor; and (v) optionally, water.

[0063] definition Unless otherwise defined, technical and scientific terms used herein have the meanings commonly understood by those skilled in the art to which the present invention pertains. In view of the guidance provided herein, any suitable materials and / or methods known to those skilled in the art can be utilized in carrying out the present invention, however, for illustrative purposes, specific materials and methods are described. Materials, reagents, and the like referred to in the following description and examples are available from commercial sources unless otherwise noted.

[0064] As used herein, the singular forms "a," "an," and "the" refer to both the singular and the plural, unless expressly stated to refer to the singular only.

[0065] As used herein, "about" when used in conjunction with a numerical value means not only the numerical value specified, but also plus or minus 10% of that numerical value. For example, "about 10" should be understood as both "10" and "from 9 to 11."

[0066] As used herein, a phrase in the form "A / B" or "A and / or B" means (A), (B), or (A and B), and a phrase in the form "at least one of A, B, and C" means (A), (B), (C), (A and B), (A and C), (B and C), or (A, B, and C).

[0067] As used herein, the terms "comprising," "including," and "containing" are used expansively to mean that the composition, method, or kit being described includes at least the elements specified, and may include other elements not specified. The phrase "consisting essentially of" is used to include those elements specifically recited, as well as additional elements that do not materially affect the basic and novel characteristics of the claimed invention, e.g., ingredients that do not substantially impair the solubility of enzalutamide in the composition or the palatability of the composition.

[0068] As used herein, "subject" refers to any mammal, including a human. For example, a subject may be suffering from or at risk of developing a condition that can be treated or prevented by enzalutamide, or may be taking enzalutamide for other purposes.

[0069] The terms "administer," "administration," and "administering," as used herein, refer to providing, giving, dispensing, and / or prescribing, such as by or under the supervision of a medical practitioner or his / her authorized agent, as well as injecting, taking, or ingesting, such as by a medical practitioner or a subject.

[0070] The terms "treat," "treating," and "treatment," as used herein, include alleviating, relieving, or ameliorating a disease or condition, or one or more symptoms thereof, regardless of whether the disease or condition is considered to be "cured" or "cured," and whether or not all symptoms are alleviated.

[0071] As used herein, the phrases "therapeutically effective amount" and "therapeutically effective dose" refer to an amount or dose that provides the specific pharmacological effect of a drug administered to a subject in need of such treatment. It is emphasized that a therapeutically effective amount is not necessarily effective in treating a target condition, even if a person skilled in the art considers such an amount or dose to be a therapeutically effective amount or dose. For convenience only, exemplary doses and therapeutically effective amounts related to adult human subjects are provided below. A person skilled in the art can adjust such amounts according to standard techniques as necessary to treat a specific subject and / or condition.

[0072] The disclosure of a particular compound under a particular category (e.g., "surfactant," "solubilizer," "co-surfactant," "precipitation retardant," etc.) is not necessarily limiting. One of ordinary skill in the art will understand that a given compound may perform more than one function in a given composition, or that the compound may perform different functions depending on the composition in which it is used.

[0073] Enzalutamide The active ingredient of the compositions described herein is enzalutamide. Enzalutamide has the chemical name 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide and the molecular formula C 21 H 16 It is F4N4O2S and has a molecular weight of 464.44. Enzalutamide is registered under the CAS Registry Number 915087-33-1. The structural formula of Enzalutamide is shown below. [ka]

[0074] The compositions described herein may contain any suitable amount of enzalutamide. For example, the compositions described herein may contain about 2.5% to about 6% w / w, such as about 2.5% w / w, about 3% w / w, about 4% w / w, about 5% w / w, about 6% w / w, and any amount therebetween. The compositions as described herein may contain about 20 mg to about 45 mg of enzalutamide per mL of the composition, for example, about 30 mg to about 45 mg of enzalutamide per mL of the composition, for example, about 20 mg, about 21 mg, about 22 mg, about 23 mg, about 24, about 25 mg, about 26 mg, about 27 mg, about 28 mg, about 29 mg, about 30 mg, about 31 mg, about 32 mg, about 33 mg, about 34 mg, about 35 mg, about 36 mg, about 37 mg, about 38 mg, about 39 mg, about 40 mg, about 41 mg, about 42 mg, about 43 mg, about 44 mg, and about 45 mg per mL of the composition. In some embodiments, the compositions as described herein contain about 15 mg of enzalutamide per mL of the composition. In some embodiments, the compositions as described herein contain about 27 mg of enzalutamide per mL of the composition. In another embodiment, the composition as described herein contains about 30 mg of enzalutamide per mL of composition. In another embodiment, the composition as described herein contains about 40 mg of enzalutamide per mL of composition.

[0075] As mentioned above, enzalutamide is typically formulated at a dose of about 160 mg / day. Thus, the compositions as described herein can provide a therapeutically effective dose (e.g., about 160 mg) in a convenient volume of the composition, such as about 3.5 mL to about 6.0 mL, e.g., about 5 mL, e.g., 6 mL. The therapeutically effective dose of enzalutamide can be provided in such a convenient volume of an oral liquid pharmaceutical composition, which is advantageous for patient convenience and can promote patient compliance with the treatment regimen, thereby improving the treatment outcome.

[0076] The compositions described herein may be provided in any dosage form suitable for oral liquid pharmaceutical compositions, including bulk dosage forms or unit dosage forms. In bulk dosage forms, a volume of the composition providing multiple doses (e.g., 150 mL or more) may be provided in a bottle. In unit dosage forms, a volume of the composition providing a single dose (e.g., 3.5-6.0 mL) may be provided in a bottle or pouch (e.g., stick pack or sachet). Alternatively, in unit dosage forms, a volume of the composition providing a single dose or a subdose thereof may be filled into one or more capsules. For example, a volume of the composition providing ¼ of the dose (e.g., 1-1.25 mL or 1.5 mL) may be filled into one capsule, such that the total dose is provided in four capsules. Similarly, a volume of the composition providing ½ of the dose (e.g., 2-2.5 mL or 3 mL) may be filled into one capsule, such that the total dose is provided in two capsules. Similarly, one capsule may be filled with a volume providing 1 / 3 of the dose (such as 1 mL of 6 mL) such that the total dose is provided in three capsules.

[0077] Thus, the compositions described herein can be packaged in unit dosage forms (unit doses) containing about 160 mg (inclusive) of enzalutamide per unit dosage form (unit dose).For example, the compositions described herein can be packaged in unit dose bottles, vials, pouches, stick packs, sachets, etc., each containing about 160 mg (inclusive).

[0078] As illustrated in the examples below, compositions as described herein may exhibit an in vitro dissolution profile of enzalutamide comparable to that of XTANDI® capsules. Additionally or alternatively, compositions as described herein may exhibit an in vivo pharmacokinetic profile comparable to that of XTANDI® capsules, as may be reflected in the mean plasma concentration-time profile following administration. Alternatively, compositions as described herein may achieve a pharmacokinetic profile that is not comparable to that of XTANDI® but is therapeutically effective, for example, for treating prostate cancer.

[0079] As mentioned above, the compositions described herein typically include (i) enzalutamide; (ii) optionally, an oil; (iii) a surfactant and / or solubilizer, (iv) a co-surfactant, (v) an antioxidant, (vi) optionally, a precipitation inhibitor; and (vii) optionally, water. In some embodiments, the compositions include (i) enzalutamide; (ii) an oil selected from one or more of vegetable oils, flavor oils, and essential oils; (iii) a surfactant, (iv) a co-surfactant, (v) an antioxidant, (vi) a solubilizer, (vii) a precipitation inhibitor, and (viii) water. In some embodiments, the compositions include (i) enzalutamide; (ii) a surfactant, (iii) a co-surfactant, (iv) an antioxidant, (v) a solubilizer, (vi) a precipitation inhibitor, and (vii) water. In some embodiments, the composition comprises (i) enzalutamide; (ii) an oil selected from one or more of vegetable oils, flavor oils, and essential oils; (iii) a surfactant, (iv) a co-surfactant, (v) an antioxidant, and (vi) a precipitation inhibitor. In some embodiments, the composition comprises (i) enzalutamide; (ii) an oil selected from one or more of vegetable oils, flavor oils, and essential oils; (iii) a surfactant, (iv) a co-surfactant, (v) an antioxidant, (vi) a solubilizer, and (vii) a precipitation inhibitor. Having described enzalutamide above, the other components are now described below.

[0080] oil The compositions described herein may optionally include oil. The oil generally acts as a vehicle or dispersant for enzalutamide, or both. The oil may be one or more selected from vegetable oils, flavor oils, and essential oils. If present, the total oil content of the compositions described herein may be about 0.5% to about 25% w / w or about 0.5% to about 20% w / w.

[0081] When present, the oil may comprise one or more vegetable oils. When present, the vegetable oil may be present in any suitable amount. For example, the composition as described herein may comprise a total amount of vegetable oil from about 3% w / w to about 20% w / w. Thus, the total amount of vegetable oil present in the composition as described herein may be from about 3% w / w to about 20% w / w or from about 3% w / w to about 15% w / w, such as about 3% w / w, about 3.5% w / w, about 4% w / w, about 4.5% w / w, about 5% w / w, about 7% w / w, about 9% w / w, about 10% w / w, about 11% w / w, about 12% w / w, about 15% w / w, about 17% w / w, or about 20% w / w, or any value therebetween.

[0082] Examples of suitable vegetable oils include, but are not limited to, corn oil, linseed oil, and rapeseed oil.Thus, for example, the composition as described herein may comprise corn oil.For example, the composition as described herein may comprise corn oil in an amount of about 3% w / w to about 20% w / w or about 3% w / w to about 15% w / w, for example, about 3.5% w / w, about 5% w / w, about 9% w / w, about 10% w / w, about 11% w / w, and about 12% w / w.

[0083] The compositions described herein may include one or more flavor oils and essential oils, which may act as both flavor and vehicle (and / or dispersing) components. When present, the flavor oil and / or essential oil may be present in any suitable amount. For example, the compositions as described herein may include a total amount of flavor oil and / or essential oil from about 0.5% w / w to about 5% w / w. Thus, the total amount of flavor oil and essential oil present in the compositions as described herein may be about 0.5% w / w, about 1.0% w / w, about 1.5% w / w, about 2.0% w / w, about 2.5% w / w, about 3.0% w / w, about 3.5% w / w, about 4.0% w / w, about 4.5% w / w, about 5.0% w / w, or any value therebetween.

[0084] Examples of suitable flavor oils include, but are not limited to, peppermint oil (which may also be considered as essential oil), licorice oil, butterscotch oil, and anise oil.Thus, for example, the composition as described herein may include peppermint oil.For example, the composition as described herein may include peppermint oil in an amount of about 0.5% w / w to about 5% w / w, for example, about 1% w / w, about 1.5% w / w, about 4.0% w / w, about 4.5% w / w, or about 5.0 w / w.

[0085] Examples of suitable essential oils include those from basil (Ocimum basilicum), bergamot (Citrus bergamia), black pepper (Piper nigrum), cassia (Cinnamomum cassia), cinnamon (Cinnamomum zeylanicum), clary sage (Salvia sclarea), clove (Eugenia caryophyllata), coriander (Coriandrum sativum), cumin (Cuminum cyminum), fennel (Foeniculum vulgare), and oleander (Coriandrum sativum). vulgare), Geranium (Pelargonium graveolens), Ginger (Zingiber officinale), Grapefruit (Citrus x paradisi), Juniper Berry (Juniperus communis), Lemon (Citrus limon), Lemongrass (Cymbopogon flexuosus), Lime (Citrus aurantifolia), Marjoram (Origanum majorana), Lemon Balm (Melissa officinalis), Oregano (Origanum vulgare), vulgare), Peppermint (Mentha piperita), Petitgrain (Citrus aurantium), Roman Chamomile (Anthemis nobilis), Rosemary (Rosmarinus officinalis), Spearmint (Mentha spicata),Examples of suitable herbs include, but are not limited to, tangerine (Citrus spicata), tangerine (Citrus reticulate), thyme (Thymus vulgaris), Japanese laurel (Citrus sinensis), and ylang (Cananga odorata).

[0086] Surfactants The compositions described herein may include one or more surfactants. Examples of suitable surfactants include those having a hydrophilic lipophilic balance (HLB) value of 4 to 16. Non-limiting examples of suitable surfactants include: Tocopherol polyethylene glycol succinate surfactants (e.g., D-α-tocopherol polyethylene glycol 1000 succinate, also known as Vitamin E TPGS and Tocophersolan); Polyoxyethylene castor oil surfactants (e.g., Polyoxyethylene 35 castor oil, also known as PEG-35 castor oil and macrogolglycerol ricinoleate, e.g., KOLLIPHOR® EL and KOLLIPHOR® ELP); polyoxyl hydrogenated castor oil surfactants (e.g., polyoxyl 40 hydrogenated castor oil, also known as macrogol glycerol hydroxystearate, e.g., KOLLIPHOR® RH40); Polyoxyl hydroxystearates surfactants (e.g., macrogol hydroxystearate (15), polyethylene glycol hydroxystearate (15), and polyoxyl 15 hydroxystearate, also known as polyoxyethylated 12-hydroxystearic acid, e.g., KOLLIPHOR® HS 15); lauroyl polyoxylglyceride and lauroyl macrogoglyceride surfactants (e.g., GELUCIRE® 44 / 14 and ACCONON® C-44); Stearoyl polyoxylglyceride and stearoyl macrogoglyceride surfactants (e.g., GELUCIRE® 50 / 13 and ACCONON® C-50); Polyoxyl stearate surfactants (e.g., polyoxyl stearate type I such as GELUCIRE® 48 / 16); oleoyl polyoxyl-6-glyceride surfactants (e.g., LABRAFIL® M 1944 CS); Linoleoyl macrogolglyceride and linoleoyl polyoxylglyceride surfactants (e.g., LABRAFIL® M 2125 CS); Glycerol monocaprylocaprate type I (e.g., CAPMUL® MCM) surfactants; propylene glycol monocaprylate type II (e.g., CAPMUL® PG-8) surfactants; and propylene glycol monolaurate type II surfactants (e.g., CAPMUL® PG-12), and Lauroyl macrogolglyceride and lauroyl polyoxylglyceride surfactants (e.g., LABRAFIL® M 2130 CS).

[0087] Thus, for example, compositions as described herein may include, but are not limited to, tocopherol polyethylene glycol succinate surfactants (e.g., D-α-tocopherol polyethylene glycol 1000 succinate, also known as Vitamin E TPGS and tocophersolan); polyoxyethylene castor oil surfactants (e.g., Polyoxyethylene 35 castor oil, also known as PEG-35 castor oil and macrogol glycerol ricinoleate, e.g., KOLLIPHOR® EL and KOLLIPHOR® ELP); polyoxyl hydrogenated castor oil surfactants (e.g., Polyoxyl 40 hydrogenated castor oil, also known as macrogol glycerol hydroxystearate, e.g., KOLLIPHOR® RH40); polyoxyl hydroxystearate surfactants (e.g., Macrogol (15) hydroxystearate, Polyethylene glycol (15) hydroxystearate, and Polyoxyl 15 hydroxystearate, also known as polyoxyethylated 12-hydroxystearic acid), such as KOLLIPHOR® HS. 15; lauroyl polyoxylglyceride and lauroyl macrogoglyceride surfactants (e.g., GELUCIRE® 44 / 14 and ACCONON® C-44); stearoyl polyoxylglyceride and stearoyl macrogoglyceride surfactants (e.g., GELUCIRE® 50 / 13 and ACCONON® C-50); and polyoxyl stearate surfactants (e.g., polyoxyl stearate type I such as GELUCIRE® 48 / 16).

[0088] When present, the surfactants may be present in any suitable amount in the compositions as described herein.For example, the compositions as described herein may contain one or more of these surfactants in a total amount of about 5% w / w to about 65% w / w, such as about 5% w / w, about 5.5% w / w, about 6% w / w, about 6.5% w / w, about 7% w / w, about 10% w / w, about 12% w / w, about 15% w / w, about 17% w / w, about 20% w / w, about 22% w / w, about 25% w / w, about 30% w / w, about 35% w / w, about 40% w / w, about 45% w / w, about 50% w / w, about 55% w / w, about 60% w / w, or about 65% w / w, or any value therebetween.When a combination of surfactants is used, each may be present in any suitable amount. For example, a composition as described herein may contain a relatively large amount of one surfactant and a relatively small amount of another surfactant, or may contain relatively equal amounts of the surfactants.

[0089] Co-surfactants The compositions described herein typically further comprise one or more surfactants as co-surfactants. The one or more co-surfactants may be selected from oleoyl polyoxyl-6-glyceride surfactants (e.g., LABRAFIL® M 1944 CS); linoleoyl macrogol glyceride and linoleoyl polyoxyl glyceride surfactants (e.g., LABRAFIL® M 2125 CS); lauroyl macrogol glyceride and lauroyl polyoxyl glyceride surfactants (e.g., LABRAFIL® M 2130 CS); propylene glycol monocaprylate type II surfactants (e.g., CAPMUL® PG-8); glycerol monocaprylate type I (e.g., CAPMUL® MCM) surfactants, and propylene glycol monolaurate type II surfactants (e.g., CAPMUL® PG-12). The one or more co-surfactants may be present in any suitable amount in the compositions as described herein. For example, compositions as described herein may contain one or more of these co-surfactants in a total amount of about 5% to about 30% w / w, or about 5% to about 25% w / w, e.g., about 5% to about 20% w / w, e.g., about 5% w / w, about 6% w / w, about 7% w / w, about 8% w / w, about 9% w / w, about 10% w / w, about 11% w / w, about 12% w / w, about 13% w / w, about 14% w / w, about 15% w / w, about 16% w / w, about 17% w / w, about 18% w / w, about 19% w / w, about 20% w / w, and any value therebetween. When combinations of co-surfactants are used, each may be present in any suitable amount. For example, a composition as described herein may contain a relatively large amount of one co-surfactant and a relatively small amount of another co-surfactant, or may contain relatively equal amounts of the co-surfactants.

[0090] In certain embodiments, the compositions as described herein include a tocopherol succinate polyethylene glycol surfactant (e.g., Vitamin E TPGS). For example, the compositions as described herein may include Vitamin E TPGS in an amount of about 5% w / w to about 55% w / w, e.g., about 6% w / w, or about 14% w / w to about 17% w / w, e.g., about 14% w / w, about 15% w / w, about 16% w / w, or about 17% w / w. In other specific embodiments, the compositions as described herein comprise a tocopherol succinate polyethylene glycol surfactant (e.g., Vitamin E TPGS) and a polyoxyethylene castor oil surfactant (e.g., a PEG-35 castor oil such as KOLLIPHOR® ELP), e.g., Vitamin E TPGS and PEG 35 castor oil (e.g., KOLLIPHOR® ELP) in a total amount of about 5% w / w to about 55% w / w, e.g., about 12% w / w or about 18% w / w Vitamin E TPGS, and about 21% w / w or about 30% w / w PEG 35 castor oil (e.g., KOLLIPHOR® ELP).

[0091] According to any of these embodiments, the composition may further comprise a co-surfactant such as an oleoyl polyoxyl-6-glyceride surfactant (e.g., LABRAFIL® M 1944 CS), for example, in an amount of about 5% w / w to about 30% w / w or about 5% w / w to about 25% w / w. For example, the composition as described herein may comprise an oleoyl polyoxyl-6-glyceride surfactant (e.g., LABRAFIL® M 1944 CS) in an amount of about 12% w / w, about 13% w / w, about 15% w / w, or about 17% w / w. In certain examples, compositions as described herein may include Vitamin E TPGS in an amount of about 5% w / w to about 55% w / w, e.g., about 6% w / w, and an oleoyl polyoxyl-6-glyceride surfactant (e.g., LABRAFIL® M 1944 CS) as a co-surfactant in an amount of about 5% w / w to about 30% w / w or about 5% w / w to about 25% w / w, e.g., about 17% w / w. Alternatively, the compositions as described herein may contain Vitamin E TPGS and PEG 35 Castor Oil (e.g., KOLLIPHOR® ELP) in a total amount of about 5% w / w to about 55% w / w (e.g., about 12% w / w Vitamin E TPGS, and about 21% PEG 35 Castor Oil (e.g., KOLLIPHOR® ELP)), and an oleoyl polyoxyl-6-glyceride surfactant (e.g., LABRAFIL® M 1944 CS) as a co-surfactant in an amount of about 5% w / w to about 30% w / w or about 5% w / w to about 25% w / w, e.g., about 13% w / w. Alternatively, the compositions as described herein may contain Vitamin E TPGS and PEG 35 Castor Oil (e.g., KOLLIPHOR® ELP) in a total amount of about 5% w / w to about 55% w / w (e.g., about 18% w / w Vitamin E TPGS, and about 30% PEG 35 Castor Oil (e.g., KOLLIPHOR® ELP)), and an oleoyl polyoxyl-6-glyceride surfactant (e.g., LABRAFIL® M 1944 CS) as a co-surfactant in an amount of about 5% w / w to about 30% w / w or about 5% w / w to about 25% w / w, e.g., about 13% w / w.Alternatively, the compositions as described herein may contain Vitamin E TPGS and PEG 35 castor oil (e.g., KOLLIPHOR® ELP) in a total amount of about 5% w / w to about 55% w / w (e.g., about 17% w / w Vitamin E TPGS and about 28% PEG 35 castor oil (e.g., KOLLIPHOR® ELP)) and an oleoyl polyoxyl-6-glyceride surfactant (e.g., LABRAFIL® M 1944 CS) as a co-surfactant in an amount of about 5% w / w to about 30% w / w or about 5% w / w to about 25% w / w, e.g., about 15% w / w.

[0092] Alternatively, the composition may further comprise a co-surfactant such as glycerol monocaprylocaprate type I surfactant (e.g., CAPMUL® MCM) in an amount of, for example, about 5% w / w to about 30% w / w or about 5% w / w to about 25% w / w. For example, the composition as described herein may comprise glycerol monocaprylocaprate type I surfactant (e.g., CAPMUL® MCM) in an amount of about 7% w / w as a co-surfactant. In a particular example, the composition as described herein may comprise vitamin E TPGS in an amount of about 5% w / w to about 55% w / w, for example, about 17% w / w, and glycerol monocaprylocaprate type I surfactant (e.g., CAPMUL® MCM) in an amount of about 5% w / w to about 30% w / w or about 5% w / w to about 25% w / w, for example, about 7% w / w as a co-surfactant.

[0093] Alternatively, the composition may further comprise a co-surfactant such as propylene glycol monocaprylate type II surfactant (e.g., CAPMUL® PG-8) in an amount of, for example, about 5% w / w to about 30% w / w or about 5% w / w to about 25% w / w. For example, the composition as described herein may comprise a propylene glycol monocaprylate type II surfactant (e.g., CAPMUL® PG-8) as a co-surfactant in an amount of about 7% w / w. In a particular example, the composition as described herein may comprise vitamin E TPGS in an amount of about 5% w / w to about 55% w / w, for example, about 17% w / w, and a propylene glycol monocaprylate type II surfactant (e.g., CAPMUL® PG-8) as a co-surfactant in an amount of about 5% w / w to about 30% w / w or about 5% w / w to about 25% w / w, for example, about 7% w / w.

[0094] Alternatively, the composition may further comprise a co-surfactant such as a propylene glycol monolaurate type II surfactant (e.g., CAPMUL® PG-12) in an amount of, for example, about 5% w / w to about 30% w / w or about 5% w / w to about 25% w / w. For example, the composition as described herein may comprise a propylene glycol monolaurate type II surfactant (e.g., CAPMUL® PG-12) as a co-surfactant in an amount of about 6% w / w or about 7% w / w. In a particular example, a composition as described herein may include vitamin E TPGS in an amount of about 5% w / w to about 55% w / w, e.g., about 17% w / w, and a propylene glycol monolaurate type II surfactant (e.g., CAPMUL® PG-12) as a co-surfactant in an amount of about 5% w / w to about 30% w / w or about 5% w / w to about 25% w / w, e.g., about 7% w / w. Alternatively, a composition as described herein may include vitamin E TPGS in an amount of about 5% w / w to about 55% w / w, e.g., about 15% w / w, and a propylene glycol monolaurate type II surfactant (e.g., CAPMUL® PG-12) as a co-surfactant in an amount of about 5% w / w to about 30% w / w or about 5% w / w to about 25% w / w, e.g., about 7% w / w. In a further alternative, the compositions as described herein may comprise Vitamin E TPGS in an amount of about 5% w / w to about 55% w / w, e.g., about 14% w / w to about 17% w / w, e.g., about 14% w / w, about 15% w / w, about 16% w / w, or about 17% w / w, and a propylene glycol monolaurate type II surfactant (e.g., CAPMUL® PG-12) as a co-surfactant in an amount of about 5% w / w to about 30% w / w or about 5% w / w to about 25% w / w, e.g., about 6% w / w or about 7% w / w.

[0095] Sedimentation Inhibitor Compositions as described herein may optionally include a precipitation inhibitor.Non-limiting examples of suitable precipitation inhibitors include one or more of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer solubilizers (e.g., SOLUPLUS®), polyoxyethylene polyoxypropylene glycol solubilizers (e.g., KOLLIPHOR® P188 or P407), polyvinyl pyrrolidone solubilizers (e.g., KOLLIDON® K-30), vinyl pyrrolidone-vinyl acetate copolymer solubilizers (e.g., KOLLIDON® VA-64), polyvinyl alcohol / polyethylene glycol graft copolymer solubilizers (e.g., KOLLICOAT® IR), hydroxypropyl methylcellulose solubilizers (also known as HMPC and hypromellose), and hypromellose acetate succinate solubilizers (e.g., AQOAT®). The precipitation inhibitor may be used in any suitable amount. For example, the composition may include one or more precipitation inhibitors in a total amount of about 0.5% w / w to about 5% w / w or about 0.5% w / w to about 1% w / w, such as about 0.5% w / w, about 0.75% w / w, about 1% w / w, about 1.5% w / w, about 2% w / w, about 2.5% w / w, about 3% w / w, about 3.5% w / w, about 4% w / w, about 4.5% w / w, about 5% w / w, and any value therebetween. For example, compositions as described herein may include a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer solubilizer (e.g., SOLUPLUS®) in an amount of about 0.5% w / w to about 5% w / w, e.g., about 0.5% w / w, or about 0.65% w / w, or about 0.75% w / w.

[0096] Co-solvents The compositions described herein may optionally include one or more co-solvents. Non-limiting examples of suitable co-solvents include diethylene glycol monoethyl ether (e.g., TRANSCUTOL® HP or TRANSCUTOL® P), tetrahydrofurfuryl alcohol polyethylene glycol ether (e.g., glycofurol), and N-methylpyrrolidone (e.g., PHARMASOLVE® V). The co-solvent may be present in any suitable amount. For example, the compositions as described herein may include about 10% w / w to about 35% w / w of the co-solvent, for example, about 10% w / w, about 15% w / w, about 19% w / w, about 20% w / w, about 25% w / w, about 30% w / w, about 35% w / w, and any value therebetween. In some embodiments, the compositions described herein include diethylene glycol monoethyl ether (e.g., TRANSCUTOL® HP or TRANSCUTOL® P) as a co-solvent, for example in an amount of about 20% w / w or 25% w / w of the composition.

[0097] Solubilizer The compositions described herein may include one or more solubilizers. Non-limiting examples of suitable solubilizers include those with an HLB value of 11-15, such as polyethylene glycol caprylic / capric glyceride solubilizers, such as polyethylene glycol caprylocaproyl polyoxylglycerides and caprylocaproyl macrogoglycerides solubilizers (e.g., ACCONON® MC8-2), polyglyceryl oleate solubilizers (e.g., polyglyceryl-10 oleate, such as CAPROL® PGE 860), polyoxyethylene sorbitan monooleate solubilizers (e.g., polyoxyethylene (20) sorbitan monooleate or polysorbate 80). In some embodiments, the composition does not include a caprylocaproyl polyoxyl-8 glyceride solubilizer / surfactant (e.g., does not include LABRASOL®, does not include LABRASOL® ALF). Embodiments other than the caprylocaproyl polyoxyl-8 glyceride surfactant / solubilizer may still (optionally) include a polyethylene glycol caprylocaproyl polyoxylglyceride / caprylocaproyl macrogoglyceride solubilizer (e.g., ACCONON® MC8 2, a polyethylene glycol caprylic / capric glyceride solubilizer).

[0098] When present, the solubilizer may be present in any suitable amount. For example, the composition as described herein may comprise a total amount of one or more solubilizers of about 10% w / w to about 65% w / w, such as about 15% w / w, about 20% w / w, about 25% w / w, about 27% w / w, about 30% w / w, about 35% w / w, about 40% w / w, about 45% w / w, about 50% w / w, about 55% w / w, about 60% w / w, about 65% w / w, or any value therebetween. When a combination of solubilizers is used, each may be present in any suitable amount.

[0099] Compositions as described herein may include a solubilizer selected from one or more of polyethylene glycol caprylocaproyl polyoxylglycerides and caprylocaproyl macrogoglyceride solubilizers (e.g., ACCONON® MC8-2), polyglyceryl oleate solubilizers (e.g., polyglyceryl-10 oleate such as CAPROL® PGE 860), polyethylene glycol caprylic / capric glyceride solubilizers such as polyoxyethylene sorbitan monooleate solubilizers (e.g., polyoxyethylene (20) sorbitan monooleate or polysorbate 80). Solubilizers, as disclosed above, may be used in relatively large amounts, for example, from about 10% to about 65% w / w. For example, compositions as described herein may include a polyethylene glycol caprylocaproyl polyoxylglyceride / caprylocaproyl macrogoglyceride solubilizer (e.g., ACCONON® MC8-2) in an amount of, for example, about 10% to about 65% w / w, e.g., about 25% w / w, about 40% w / w, about 55% w / w, or about 60% w / w.

[0100] Thus, for example, in some embodiments, the compositions as described herein include a combination of a solubilizer and a precipitation retardant, such as a polyethylene glycol caprylocaproyl polyoxylglyceride / caprylocaproyl macrogoglyceride solubilizer (e.g., ACCONON® MC8-2) and a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant (e.g., SOLUPLUS®). For example, a composition as described herein may comprise about 25% w / w, about 40% w / w, about 55% w / w, or about 60% w / w, e.g., about 55% w / w to about 60% w / w of a polyethylene glycol caprylocaproyl polyoxylglyceride / caprylocaproyl macrogoglyceride solubilizer (e.g., ACCONON® MC8-2) and about 0.5% w / w to about 0.75% w / w, e.g., about 0.5% w / w, or about 0.65% w / w, or about 0.75% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer solubilizer (e.g., SOLUPLUS®).

[0101] Antioxidants The compositions described herein typically include one or more antioxidants. Non-limiting examples of suitable antioxidants include DL-methionine, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), arginine, cysteine, ascorbic palmitate, sodium metabisulfite, sodium thiosulfate, propyl gallate, gamma linoleic acid, ascorbic acid, ethylenediaminetetraacetic acid (EDTA), and alpha tocopherol. Thus, according to any of the foregoing embodiments, the compositions as described herein may include an antioxidant. For example, the compositions as described herein may include one or more selected from DL-methionine, BHA, and BHT. In some embodiments, the compositions may include one or more of DL-methionine, arginine, and cysteine. In some embodiments, the compositions may include DL-methionine. The antioxidant may be present in any suitable amount. For example, compositions as described herein may contain one or more antioxidants in a total amount of about 0.01% to about 1.0% w / w, such as about 0.05% to about 1.0% w / w (including any value therebetween).

[0102] Sweeteners / Flavors The compositions described herein may optionally include one or more sweeteners and / or one or more flavoring agents. Examples of suitable sweeteners include, but are not limited to, sucralose, glycyrrhizic acid and its salts (e.g., ammonium glycyrrhizinate), saccharin, aspartame, acesulfame potassium, cyclamate, erythritol, and neotame. Thus, according to any of the foregoing embodiments, the compositions as described herein may include a sweetener. For example, the compositions as described herein may include one or more sweeteners selected from sucralose and ammonium glycyrrhizinate. The sweeteners may be present in any suitable amount. For example, the compositions as described herein may include one or more sweeteners in a total amount of about 0.015% w / w to about 0.75% w / w or about 0.015% w / w to about 2% w / w (including any value therebetween).

[0103] Examples of suitable flavoring agents include, but are not limited to, vanilla flavor, banana flavor, grapefruit flavor, strawberry flavor, raspberry flavor, bubblegum flavor, and caramel flavor. Thus, according to any of the foregoing embodiments, the composition as described herein may include a flavoring agent. For example, the composition as described herein may include vanilla flavor and banana flavor. The flavoring agent may be present in any suitable amount. For example, the composition as described herein may include one or more flavoring agents in a total amount of about 0.01% w / w to about 1.0% w / w, including any value therebetween.

[0104] water In some embodiments, the compositions as described herein include water (e.g., purified water). In some embodiments, the water is present in an amount of about 1% to about 5% w / w, e.g., about 1% w / w, about 1.5% w / w, about 2% w / w, about 2.5% w / w, about 3% w / w, about 3.5% w / w, about 4% w / w, about 4.5% w / w, and 5% w / w.

[0105] Additional Ingredients The compositions as described herein may optionally further comprise one or more additional pharma- ceutically acceptable components suitable for use in oral liquid pharmaceutical compositions.For example, the compositions as described herein may optionally further comprise one or more pharma- ceutically acceptable excipients, such as viscosity adjusters (e.g., thickeners), diluents, pH adjusters, colorants, other flavors, other taste-masking agents, other preservatives, etc.

[0106] Excluded ingredients As mentioned above, WO 2018 / 037310 discloses an enzalutamide composition containing a large amount of LABRASOL (registered trademark) and propylene glycol. In particular, WO 2018 / 037310 discloses an enzalutamide composition containing one or more of LABRASOL (registered trademark), LABRASOL (registered trademark) ALF, polyethylene glycol 300 (PEG300), and polyethylene glycol 400 (PEG400) as "surfactants", and also discloses an enzalutamide composition containing propylene glycol and / or ethanol as a solvent. The composition of the present disclosure does not require such components. Thus, in certain embodiments of any of the embodiments disclosed herein, the composition does not include a caprylocaproyl polyoxyl-8 glyceride surfactant / solubilizer as disclosed in WO 2018 / 037310 (e.g., LABRASOL®, LABRASOL® ALF, which are referred to as surfactants in WO 2018 / 037310 but may also be considered to be solubilizers) and does not include polyethylene glycol (e.g., PEG 300, PEG 400). In further specific embodiments of any of the embodiments disclosed herein, the composition additionally or alternatively does not include propylene glycol and does not include ethanol. That is, in certain embodiments of any of the embodiments disclosed herein, the composition does not include a caprylocaproyl polyoxyl-8 glyceride surfactant / solubilizer (e.g., LABRASOL®, LABRASOL® ALF) and does not include polyethylene glycol (e.g., PEG 300, PEG 400). In further specific embodiments of any of the embodiments disclosed herein, the composition does not include propylene glycol and does not include ethanol. In further specific embodiments of any of the embodiments disclosed herein, the composition does not include any caprylocaproyl polyoxyl-8 glyceride surfactant / solubilizer (e.g., LABRASOL®, LABRASOL® ALF), polyethylene glycol, and ethanol.In other specific embodiments of any of the embodiments disclosed herein, the composition does not include the amount of caprylocaproyl polyoxyl-8 glyceride surfactant / solubilizer (e.g., LABRASOL®, LABRASOL® ALF), polyethylene glycol (e.g., PEG 300, PEG 400), propylene glycol, or ethanol used in the compositions of WO 2018 / 037310. For example, in specific embodiments of any of the embodiments disclosed herein, the composition does not include about 30% to about 90% w / w of one or more of caprylocaproyl polyoxyl-8 glyceride surfactant / solubilizer and polyethylene glycol. In further specific embodiments of any of the embodiments disclosed herein, the composition additionally or alternatively does not include propylene glycol and does not include ethanol. As noted above, embodiments other than caprylocaproyl polyoxyl-8 glyceride surfactant / solubilizers (e.g., LABRASOL®, LABRASOL® ALF) may still (optionally) include a polyethylene glycol caprylic / capric glyceride solubilizer (e.g., ACCONON® MC8-2, a polyethylene glycol caprylic / capric glyceride solubilizer).

[0107] composition The following are disclosed as specific exemplary embodiments of the compositions as described herein.

[0108] In one aspect, an oral liquid pharmaceutical composition of enzalutamide is provided, (i) about 2.5% to about 6% w / w of enzalutamide; (ii) optionally, from about 0.5% to about 25% w / w of an oil selected from one or more of vegetable oils, flavor oils, and essential oils; (iii) from about 5% to about 85% w / w of a surfactant and / or a solubilizer, one or both of the surfactant and solubilizer, the surfactant comprising one or more selected from tocopherol polyethylene glycol succinate surfactants, polyoxyethylene castor oil surfactants, polyoxyl hydrogenated castor oil surfactants, polyoxyl hydroxystearic acid surfactants, lauroyl polyoxylglyceride and lauroyl macrogoglyceride surfactants, stearoyl polyoxylglyceride and stearoyl macrogoglyceride surfactants, and polyoxyl stearate surfactants, and the solubilizer comprising one or more selected from polyethylene glycol caprylic / capric acid glyceride solubilizers, polyglyceryl oleate solubilizers, and polyoxyethylene sorbitan monooleate solubilizers; (iv) from about 5% to about 25% w / w of a co-surfactant selected from one or more of propylene glycol monolaurate type II surfactants, oleoyl polyoxyl-6-glyceride surfactants, linoleoyl macrogol glyceride and linoleoyl polyoxyl glyceride surfactants, lauroyl macrogol glyceride and lauroyl polyoxyl glyceride surfactants, glycerol monocaprylocaprate type I surfactants, and propylene glycol monocaprylate type II surfactants; (v) about 0.01% to about 1% w / w of an antioxidant comprising one or more selected from DL-methionine, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), arginine, cysteine, ascorbic palmitate, sodium metabisulfite, sodium thiosulfate, propyl gallate, gamma linolenic acid, ethylenediaminetetraacetic acid (EDTA), ascorbic acid, and alpha tocopherol; (vi) optionally, from about 0.5% to about 5% w / w of a precipitation inhibitor selected from one or more of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer solubilizers, polyoxyethylene polyoxypropylene glycol solubilizers, polyvinyl pyrrolidone solubilizers, vinyl pyrrolidone-vinyl acetate copolymer solubilizers, polyvinyl alcohol / polyethylene glycol graft copolymer solubilizers, hydroxypropyl methylcellulose solubilizers, and hypromellose acetate succinate solubilizers; and (vii) optionally containing water (e.g., about 1% to about 5% w / w water).

[0109] In another aspect, an oral liquid pharmaceutical composition of enzalutamide is provided, (i) about 2.5% to about 6% w / w of enzalutamide; (ii) optionally, from about 0.5% to about 25% w / w of an oil selected from one or more of vegetable oils, flavor oils, and essential oils; (iii) from about 5% to about 65% w / w of surfactants, including tocopherol polyethylene glycol succinate surfactants (e.g., D-α-tocopherol polyethylene glycol 1000 succinate, also known as Vitamin E TPGS and tocophersolan); polyoxyethylene castor oil surfactants (e.g., Polyoxyethylene 35 castor oil, also known as PEG-35 castor oil and macrogol glycerol ricinoleate, e.g., KOLLIPHOR® EL and KOLLIPHOR® ELP); polyoxyl hydrogenated castor oil surfactants (e.g., Polyoxyl 40 hydrogenated castor oil, also known as macrogol glycerol hydroxystearate, e.g., KOLLIPHOR® RH40); polyoxyl hydroxystearates surfactants (e.g., Macrogol (15) Hydroxystearate, Polyethylene Glycol (15) Hydroxystearate, and Polyoxyl 15 Hydroxystearate, also known as Polyoxyethylated 12-Hydroxystearic Acid, e.g., KOLLIPHOR® HS 15); surfactants comprising one or more selected from lauroyl polyoxylglyceride and lauroyl macrogoglyceride surfactants (e.g., GELUCIRE® 44 / 14 and ACCONON® C-44); stearoyl polyoxylglyceride and stearoyl macrogoglyceride surfactants (e.g., GELUCIRE® 50 / 13 and ACCONON® C-50); and polyoxyl stearate surfactants (e.g., polyoxyl stearate type I such as GELUCIRE® 48 / 16); (iv) from about 5% to about 30% w / w of a co-surfactant selected from one or more of propylene glycol monolaurate type II surfactants (e.g., CAPMUL® PG-12), oleoyl polyoxyl-6-glyceride surfactants (e.g., LABRAFIL® M 1944 CS), linoleoyl macrogol glyceride and linoleoyl polyoxyl glyceride surfactants (e.g., LABRAFIL® M 2125 CS), lauroyl macrogol glyceride and lauroyl polyoxyl glyceride surfactants (e.g., LABRAFIL® M 2130 CS), propylene glycol monocaprylate type II (e.g., CAPMUL® PG-8) surfactants, and glycerol monocaprylate type I surfactants (e.g., CAPMUL® MCM); (v) about 0.01% to about 1% w / w of an antioxidant comprising one or more selected from DL-methionine, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), arginine, cysteine, ascorbic palmitate, sodium metabisulfite, sodium thiosulfate, propyl gallate, gamma linolenic acid, ethylenediaminetetraacetic acid (EDTA), ascorbic acid, and alpha tocopherol; (vi) optionally, from about 0.5% to about 5% w / w of a precipitation inhibitor selected from one or more of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer solubilizers (e.g., SOLUPLUS®), polyoxyethylene polyoxypropylene glycol solubilizers (e.g., KOLLIPHOR® 188 or P407), polyvinylpyrrolidone solubilizers (e.g., KOLLIDON® K-30), vinylpyrrolidone-vinyl acetate copolymer solubilizers (e.g., KOLLIDON® VA-64), polyvinyl alcohol / polyethylene glycol graft copolymer solubilizers (e.g., KOLLICOAT® IR), HMPC solubilizers, and hypromellose acetate succinate solubilizers (e.g., AQOAT®); and (vii) optionally, containing about 1% to about 5% w / w water;

[0110] When present, the oil may comprise from about 0.5% to about 20% w / w of the composition, optionally comprising from about 0.5% to about 5% w / w of a flavor or essential oil and from about 3% to about 15% w / w of a vegetable oil. Additionally or alternatively, the composition may comprise from about 5% to about 50% w / w of a surfactant. Additionally or alternatively, the composition may comprise from about 5% to about 20% w / w of a co-surfactant. Additionally or alternatively, the composition may optionally comprise from about 0.5% to about 1% w / w of a sedimentation inhibitor.

[0111] As mentioned above, the composition as described herein may include a combination of surfactants, for example, a combination of any two or more of the surfactants listed in (iii) above. In some embodiments that include a combination of surfactants, one of the surfactants is a polyoxyethylene castor oil surfactant (e.g., PEG-35 castor oil, such as KOLLIPHOR® ELP). For example, the composition as described herein may include a tocopherol succinate polyethylene glycol surfactant (e.g., vitamin E TPGS) and a polyoxyethylene castor oil surfactant (e.g., PEG-35 castor oil, such as KOLLIPHOR® ELP). Alternatively, the composition as described herein may include a single type of surfactant, such as a tocopherol succinate polyethylene glycol surfactant (e.g., vitamin E TPGS).

[0112] In addition to one or more surfactants, the compositions described herein further comprise a co-surfactant.For example, the compositions can comprise a tocopherol succinate polyethylene glycol surfactant (e.g., Vitamin E TPGS), a polyoxyethylene castor oil surfactant (e.g., PEG-35 castor oil, such as KOLLIPHOR® ELP), and an oleoyl polyoxyl-6-glyceride co-surfactant (e.g., LABRAFIL® M 1944 CS).In another example, the compositions can comprise a tocopherol succinate polyethylene glycol surfactant (e.g., Vitamin E TPGS) and an oleoyl polyoxyl-6-glyceride co-surfactant (e.g., LABRAFIL® M 1944 CS).In another example, the compositions can comprise a tocopherol succinate polyethylene glycol surfactant (e.g., Vitamin E TPGS) and an oleoyl polyoxyl-6-glyceride co-surfactant (e.g., LABRAFIL® M 1944 CS).In another example, the compositions can comprise a tocopherol succinate polyethylene glycol surfactant (e.g., Vitamin E TPGS) and a glycerol monocaprylocaprate type I co-surfactant (e.g., CAPMUL® MCM). In another example, the composition may include a tocopherol polyethylene glycol succinate surfactant (e.g., Vitamin E TPGS) and a propylene glycol monocaprylate Type I co-surfactant (e.g., CAPMUL® PG-8). In another example, the composition may include a tocopherol polyethylene glycol succinate surfactant (e.g., Vitamin E TPGS) and a propylene glycol monolaurate Type II co-surfactant (e.g., CAPMUL® PG-12).

[0113] In some embodiments, the composition further comprises about 10% to about 35% w / w of a co-solvent selected from one or more of diethylene glycol monoethyl ether (e.g., TRANSCUTOL® HP or TRANSCUTOL® P), tetrahydrofurfuryl alcohol polyethylene glycol ether (e.g., glycofurol), and N-methylpyrrolidone (e.g., PHARMASOLVE™ V).

[0114] In some embodiments, the composition comprises, or further comprises, about 10% to about 65% w / w solubilizers including one or more selected from polyethylene glycol caprylic / capric glyceride solubilizers such as polyethylene glycol caprylocaproyl polyoxylglycerides and caprylocaproyl macrogoglyceride solubilizers (e.g., ACCONON® MC8-2), polyglyceryl oleate solubilizers (e.g., polyglyceryl-10 oleate such as CAPROL® PGE 860), and polyoxyethylene sorbitan monooleate solubilizers (e.g., polyoxyethylene (20) sorbitan monooleate or polysorbate 80).

[0115] In any embodiment, the oil may include peppermint oil as the flavor oil and corn oil as the vegetable oil; the surfactant may be a tocopherol succinate polyethylene glycol surfactant (e.g., Vitamin E TPGS); the co-surfactant may be an oleoyl polyoxyl-6-glyceride surfactant (e.g., LABRAFIL® M 1944 CS), and the settling retardant may be a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer solubilizer (e.g., SOLUPLUS®).

[0116] Alternatively, the oil may include peppermint oil as the flavor oil and corn oil as the vegetable oil; the surfactant may be a tocopherol succinate polyethylene glycol surfactant (e.g., Vitamin E TPGS) and a polyoxyethylene castor oil surfactant (e.g., PEG-35 castor oil such as KOLLIPHOR® ELP); the co-surfactant may be an oleoyl polyoxyl-6-glyceride surfactant (e.g., LABRAFIL® M 1944 CS), and the settling retardant may be a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer solubilizer (e.g., SOLUPLUS®).

[0117] Alternatively, the oil may include peppermint oil as the flavor oil and corn oil as the vegetable oil; the surfactant may be a tocopherol succinate polyethylene glycol surfactant (e.g., Vitamin E TPGS); the co-surfactant may be a propylene glycol monocaprylate Type II surfactant (e.g., CAPMUL® PG-8), and the precipitation retardant may be a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer solubilizer (e.g., SOLUPLUS®).

[0118] Alternatively, the oil may include peppermint oil as the flavor oil and corn oil as the vegetable oil; the surfactant may be a tocopherol polyethylene glycol succinate surfactant (e.g., Vitamin E TPGS); the co-surfactant may be a propylene glycol monolaurate Type II surfactant (e.g., CAPMUL® PG-8), and the precipitation retardant may be a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer solubilizer (e.g., SOLUPLUS®).

[0119] Alternatively, the oil may include peppermint oil as the flavor oil and corn oil as the vegetable oil; the surfactant may be a tocopherol polyethylene glycol succinate surfactant (e.g., Vitamin E TPGS); the co-surfactant may be a propylene glycol monolaurate Type II surfactant (e.g., CAPMUL® PG-12), and the precipitation retardant may be a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer solubilizer (e.g., SOLUPLUS®).

[0120] In some embodiments, the composition comprises: (i) about 2.5% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 10% w / w vegetable oil; (iv) about 7% w / w of propylene glycol monolaurate type II cosurfactant; (v) about 15% w / w of a tocopherol succinate polyethylene glycol surfactant; (vi) about 60% w / w polyethylene glycol caprylic / capric glyceride solubilizer; (vii) about 0.5% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) antioxidants; (ix) optionally a sweetening agent; (x) optionally, a flavoring agent; and (xi) Contains water in an amount of about 1.5% w / w.

[0121] In the above specific embodiment, the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monolaurate type II co-surfactant is CAPMUL® PG-12; the tocopherol succinate polyethylene glycol surfactant is D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; and the antioxidant comprises one or more selected from DL methionine, BHA, and BHT. In further specific embodiments, the sweetener is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring is present and comprises vanilla and banana.

[0122] In other particular embodiments, the composition comprises: (i) about 2.5% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (Iii) about 10% w / w of vegetable oil; (iv) about 7% w / w of propylene glycol monolaurate type II cosurfactant; (v) about 15% w / w of a tocopherol succinate polyethylene glycol surfactant; (vi) about 60% w / w polyethylene glycol caprylic / capric glyceride solubilizer; (vii) about 0.5% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) antioxidants; (ix) optionally a sweetening agent; (x) optionally, a flavoring agent; and (xi) Contains water in an amount of about 3% w / w.

[0123] In certain of the foregoing embodiments, the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monolaurate type II co-surfactant is CAPMUL® PG-12; the tocopherol succinate polyethylene glycol surfactant is D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; and the antioxidant comprises DL-methionine. In further particular embodiments, the sweetener is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla and banana.

[0124] In other particular embodiments, the composition comprises: (i) about 2.5% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 10% w / w vegetable oil; (iv) about 7% w / w of propylene glycol monolaurate type II cosurfactant; (v) about 15% w / w of a tocopherol succinate polyethylene glycol surfactant; (vi) about 60% w / w polyethylene glycol caprylic / capric glyceride solubilizer; (vii) about 0.5% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) antioxidants; (ix) optionally a sweetening agent; (x) optionally, a flavoring agent; and (xi) Contains water in an amount of about 1.5% w / w.

[0125] In certain of the foregoing embodiments, the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monolaurate type II co-surfactant is CAPMUL® PG-12; the tocopherol succinate polyethylene glycol surfactant is D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; and the antioxidant comprises DL-methionine. In further particular embodiments, the sweetener is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla and banana.

[0126] In other particular embodiments, the composition comprises: (i) about 2.5% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 10% w / w vegetable oil; (iv) about 7% w / w of propylene glycol monolaurate type II cosurfactant; (v) about 15% w / w of a tocopherol succinate polyethylene glycol surfactant; (vi) about 60% w / w polyethylene glycol caprylic / capric glyceride solubilizer; (vii) antioxidants; (viii) optionally a sweetening agent; (ix) optionally, a flavoring agent; and (x) Contains water in an amount of about 3% w / w.

[0127] In certain of the foregoing embodiments, the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monolaurate type II co-surfactant is CAPMUL® PG-12; the tocopherol succinate polyethylene glycol surfactant is D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; and the antioxidant comprises DL-methionine. In further particular embodiments, the sweetener is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla and banana.

[0128] In other particular embodiments, the composition comprises: (i) about 2.5% w / w enzalutamide; (ii) about 7% w / w of propylene glycol monolaurate type II co-surfactant; (iii) about 15% w / w of a tocopherol succinate polyethylene glycol surfactant; (iv) about 60% w / w polyethylene glycol caprylic / capric glyceride solubilizer; (v) about 0.5% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (vi) antioxidants; (vii) optionally a sweetening agent; (viii) optionally, a flavoring agent; and (ix) Contains water in an amount of about 3% w / w.

[0129] In certain of the foregoing embodiments, the propylene glycol monolaurate type II co-surfactant is CAPMUL® PG-12; the tocopherol succinate polyethylene glycol surfactant is D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; and the antioxidant comprises DL methionine. In further particular embodiments, the sweetener is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla and banana.

[0130] In other particular embodiments, the composition comprises: (i) about 2.5% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 10% w / w vegetable oil; (iv) about 7% w / w of propylene glycol monolaurate type II cosurfactant; (v) about 15% w / w of a tocopherol succinate polyethylene glycol surfactant; (vi) about 60% w / w polyethylene glycol caprylic / capric glyceride solubilizer; (vii) about 0.5% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) antioxidants; (ix) optionally a sweetening agent; (x) optionally, a flavoring agent; and (xi) Contains water in an amount of about 3% w / w.

[0131] In certain of the foregoing embodiments, the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monolaurate type II co-surfactant is CAPMUL® PG-12; the tocopherol succinate polyethylene glycol surfactant is D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; and the antioxidant comprises arginine or cysteine. In further particular embodiments, the sweetener is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate, and the flavoring is present and comprises vanilla and banana.

[0132] In other particular embodiments, the composition comprises: (i) about 2.5% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 10% w / w vegetable oil; (iv) about 7% w / w of propylene glycol monolaurate type II cosurfactant; (v) about 15% w / w of a tocopherol succinate polyethylene glycol surfactant; (vi) about 60% w / w polyethylene glycol caprylic / capric glyceride solubilizer; (vii) about 0.5% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) antioxidants; (ix) optionally a sweetening agent; (x) optionally, a flavoring agent; and (xi) Contains water in an amount of about 1.5% w / w.

[0133] In certain of the foregoing embodiments, the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monolaurate type II co-surfactant is CAPMUL® PG-12; the tocopherol succinate polyethylene glycol surfactant is D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; and the antioxidant comprises DL-methionine. In further particular embodiments, the sweetener is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla and banana.

[0134] In other particular embodiments, the oral liquid pharmaceutical composition comprises: (i) about 3% w / w enzalutamide; (ii) about 1.0% w / w of flavor oil; (iii) about 3.5% w / w vegetable oil; (iv) about 13% w / w of an oleoyl polyoxyl-6-glyceride co-surfactant, such as LABRAFIL® M 1944 CS; (v) about 12% w / w of a tocopherol succinate polyethylene glycol surfactant, e.g., Vitamin E TPGS; (vi) about 20% w / w of a diethylene glycol monoethyl ether co-solvent, such as TRANSCUTOL® HP or TRANSCUTOL® P; (vii) about 26% w / w of a polyethylene glycol caprylic / capric glyceride solubilizer such as caprylocaproyl polyoxylglyceride and caprylocaproyl macrogoglyceride solubilizer, e.g., ACCONON® MC8-2; (viii) about 0.75% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor, e.g., SOLUPLUS®; (ix) a polyoxyethylene castor oil surfactant such as about 21% w / w PEG-35 castor oil, e.g., KOLLIPHOR® ELP; (x) antioxidants; (xi) optionally a sweetening agent; and (xii) optionally comprising a flavoring agent.

[0135] In further specific embodiments of the foregoing, the flavor oil is peppermint oil; the vegetable oil is corn oil; the oleoyl polyoxyl-6-glyceride co-surfactant is LABRAFIL® M 1944 CS; the tocopherol succinate polyethylene glycol surfactant is Vitamin E TPGS; the diethylene glycol monoethyl ether co-solvent is TRANSCUTOL® HP; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; the polyoxyethylene castor oil surfactant is KOLLIPHOR® ELP; the antioxidant comprises one or more selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT); the sweetening agent is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla.

[0136] In some embodiments, an oral liquid pharmaceutical composition of enzalutamide as described herein comprises: (i) about 4% w / w of enzalutamide; (ii) about 1.5% w / w of flavor oil; (iii) about 5% w / w vegetable oil; (iv) about 17% w / w of an oleoyl polyoxyl-6-glyceride surfactant, such as LABRAFIL® M 1944 CS; (v) a tocopherol polyethylene glycol succinate surfactant, such as D-α-tocopherol polyethylene glycol 1000 succinate surfactant (vitamin E TPGS), at about 6% w / w; (vi) about 25% w / w of a diethylene glycol monoethyl ether co-solvent, such as TRANSCUTOL® HP or TRANSCUTOL® P; (vii) about 40% w / w of a caprylocaproyl polyoxylglyceride and caprylocaproyl macrogoglyceride solubilizer or a polyethylene glycol caprylic / capric glyceride solubilizer such as ACCONON® MC8-2; (viii) about 0.5% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor, e.g., SOLUPLUS®; (ix) antioxidants; (x) optionally a sweetening agent; and (xi) optionally containing a flavoring agent.

[0137] In further specific embodiments of the foregoing, the flavor oil is peppermint oil; the vegetable oil is corn oil; the oleoyl polyoxyl-6-glyceride surfactant is LABRAFIL® M 1944 CS; the tocopherol succinate polyethylene glycol surfactant is Vitamin E TPGS; the diethylene glycol monoethyl ether cosolvent is TRANSCUTOL® HP; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor is SOLUPLUS®; the antioxidant comprises one or more selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT); the sweetening agent is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla.

[0138] In certain embodiments, the oral liquid pharmaceutical composition comprises: (i) about 3% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 12% w / w vegetable oil; (iv) about 13% w / w of an oleoyl polyoxyl-6-glyceride co-surfactant, such as LABRAFIL® M 1944 CS; (v) about 18% w / w of a tocopherol succinate polyethylene glycol surfactant, e.g., Vitamin E TPGS; (vi) about 20% w / w of a diethylene glycol monoethyl ether co-solvent, such as TRANSCUTOL® HP or TRANSCUTOL® P; (vii) about 0.75% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor, e.g., SOLUPLUS®; (viii) a polyoxyethylene castor oil surfactant such as about 30% w / w PEG-35 castor oil, e.g., KOLLIPHOR® ELP; (x) antioxidants; (xi) optionally a sweetening agent; and (xii) optionally comprising a flavoring agent.

[0139] In certain embodiments, the flavor oil is peppermint oil; the vegetable oil is corn oil; the oleoyl polyoxyl-6-glyceride co-surfactant is LABRAFIL® M 1944 CS; the tocopherol succinate polyethylene glycol surfactant is Vitamin E TPGS; the diethylene glycol monoethyl ether cosolvent is TRANSCUTOL® HP; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; the polyoxyethylene castor oil surfactant is KOLLIPHOR® ELP; the antioxidant comprises one or more selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT); the sweetener is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla.

[0140] In some embodiments, an oral liquid pharmaceutical composition of enzalutamide as described herein comprises: (i) about 3% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 11% w / w vegetable oil; (iv) about 7% w / w of glycerol monocaprylocaprate type I co-surfactant, e.g., CAPMUL® MCM; (v) tocopherol polyethylene glycol succinate surfactant, such as D-α-tocopherol polyethylene glycol 1000 succinate surfactant (vitamin E TPGS), at about 17% w / w; (vi) about 55% w / w of a caprylocaproyl polyoxylglyceride and caprylocaproyl macrogoglyceride solubilizer or a polyethylene glycol caprylic / capric glyceride solubilizer such as ACCONON® MC8-2; (vii) about 0.5% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor, e.g., SOLUPLUS®; (viii) antioxidants; (ix) optionally a sweetening agent; and (x) optionally, flavoring agents.

[0141] In further specific embodiments of the foregoing, the flavor oil is peppermint oil; the vegetable oil is corn oil; the glycerol monocaprylocaprate Type I co-surfactant is CAPMUL® MCM; the tocopherol succinate polyethylene glycol surfactant is Vitamin E TPGS; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; the antioxidant comprises one or more selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT); the sweetener is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla.

[0142] In some embodiments, an oral liquid pharmaceutical composition of enzalutamide as described herein comprises: (i) about 3% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 11% w / w vegetable oil; (iv) about 7% w / w of a propylene glycol monocaprylate type II co-surfactant, such as CAPMUL® PG-8; (v) tocopherol polyethylene glycol succinate surfactant, such as D-α-tocopherol polyethylene glycol 1000 succinate surfactant (vitamin E TPGS), at about 17% w / w; (vi) about 55% w / w of a caprylocaproyl polyoxylglyceride and caprylocaproyl macrogoglyceride solubilizer or a polyethylene glycol caprylic / capric glyceride solubilizer such as ACCONON® MC8-2; (vii) about 0.5% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor, e.g., SOLUPLUS®; (viii) antioxidants; (ix) optionally a sweetening agent; and (x) optionally, flavoring agents.

[0143] In further specific embodiments of the foregoing, the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monocaprylate type II co-surfactant is CAPMUL® PG-8; the tocopherol succinate polyethylene glycol surfactant is Vitamin E TPGS; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; the antioxidant comprises one or more selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT); the sweetening agent is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla.

[0144] In some embodiments, an oral liquid pharmaceutical composition of enzalutamide as described herein comprises: (i) about 3% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 11% w / w vegetable oil; (iv) about 7% w / w of a propylene glycol monolaurate type II cosurfactant, such as CAPMUL® PG-12; (v) tocopherol polyethylene glycol succinate surfactant, such as D-α-tocopherol polyethylene glycol 1000 succinate surfactant (vitamin E TPGS), at about 17% w / w; (vi) about 55% w / w of a caprylocaproyl polyoxylglyceride and caprylocaproyl macrogoglyceride solubilizer or a polyethylene glycol caprylic / capric glyceride solubilizer such as ACCONON® MC8-2; (vii) about 0.5% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor, e.g., SOLUPLUS®; (viii) antioxidants; (ix) optionally a sweetening agent; and (x) optionally, flavoring agents.

[0145] In further specific embodiments of the foregoing, the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monolaurate type II co-surfactant is CAPMUL® PG-12; the tocopherol succinate polyethylene glycol surfactant is Vitamin E TPGS; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; the antioxidant comprises one or more selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT); the sweetening agent is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla.

[0146] In some embodiments, an oral liquid pharmaceutical composition of enzalutamide as described herein comprises: (i) about 3% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 12% w / w vegetable oil; (iv) about 15% w / w of an oleoyl polyoxyl-6-glyceride co-surfactant; (v) about 17% w / w of a tocopherol succinate polyethylene glycol surfactant; (vi) about 19% w / w diethylene glycol monoethyl ether co-solvent; (vii) about 0.75% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) about 28% w / w polyoxyethylene castor oil surfactant; (ix) antioxidants; (x) optionally a sweetening agent; and (xi) optionally containing a flavoring agent.

[0147] In further specific embodiments of the foregoing, the flavor oil is peppermint oil; the vegetable oil is corn oil; the oleoyl polyoxyl-6-glyceride co-surfactant is LABRAFIL® M 1944 CS; the tocopherol succinate polyethylene glycol surfactant is Vitamin E TPGS; the diethylene glycol monoethyl ether cosolvent is TRANSCUTOL® HP; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; the polyoxyethylene castor oil surfactant is KOLLIPHOR® ELP; the antioxidant comprises one or more selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT); the sweetening agent is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla.

[0148] In some embodiments, an oral liquid pharmaceutical composition of enzalutamide as described herein comprises: (i) about 3% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 10% w / w vegetable oil; (iv) about 7% w / w of propylene glycol monolaurate type II cosurfactant; (v) about 15% w / w of a tocopherol succinate polyethylene glycol surfactant; (vi) about 60% w / w polyethylene glycol caprylic / capric glyceride solubilizer; (vii) about 0.5% w / w of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) antioxidants; (ix) optionally a sweetening agent; and (x) optionally, flavoring agents.

[0149] In further specific embodiments of the foregoing, the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monolaurate type II co-surfactant is CAPMUL® PG-12; the tocopherol succinate polyethylene glycol surfactant is D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation retardant is SOLUPLUS®; the antioxidant comprises one or more selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT); the sweetening agent is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla.

[0150] Treatment method / use The present disclosure also provides the use of the compositions described herein in a method of treatment comprising orally administering a liquid oral pharmaceutical enzalutamide composition as described herein to a subject in need thereof. For example, the subject may be a human subject suffering from prostate cancer, typically a male subject. The prostate cancer may be advanced prostate cancer, including prostate cancer that does not respond to hormone therapy or surgical procedures that reduce testosterone, or that has spread to other parts of the body. The composition may be administered in any therapeutically effective dose by any suitable administration regimen. For example, the composition may be administered once a day in an amount that provides a daily dose of about 160 mg of enzalutamide. EXAMPLES

[0151] The following specific examples are included as illustrative examples of the compositions described herein. These examples are not intended to limit the scope of the present disclosure in any way. Other aspects of the present disclosure will be apparent to those skilled in the art to which the present disclosure pertains.

[0152] Example 1 Formulations containing 160 mg of enzalutamide per unit dose of the formulation were prepared using the ingredients shown in Tables 1, 2, 3 and 4 below.

[0153] [Table 1]

[0154] [Table 2]

[0155] [Table 3]

[0156] [Table 4]

[0157] [Table 5]

[0158] [Table 6]

[0159] The in vitro dissolution and in vivo pharmacokinetic properties of the formulations were evaluated using four XTANDI® capsules per dissolution vessel as a reference product. As noted above, XTANDI® capsules are soft gelatin capsules containing 40 mg of enzalutamide in a liquid formulation.

[0160] In vitro dissolution testing was performed according to the USP Type II paddle method at 50 rpm in 900 mL of 0.1 N HCl with 0.3% cetyltrimethylammonium bromide (CTAB) dissolution medium maintained at 37° C.±0.5° C. The release profiles of formulations 1 and 2 are shown in FIG. 1. The release profiles of formulations 3, 4, 5, and 6 are shown in FIG. 2. The release profiles of formulations 7, 8, and 9 are shown in FIG. 3. The release profiles of formulations 10, 11, 12, 13, and 14 are shown in FIG. 8. The release profiles of formulations 15, 16, and 17 are shown in FIG. 9. The formulations showed complete release of enzalutamide and, when compared to XTANDI® capsules, showed similar release of enzalutamide.

[0161] In vitro dissolution testing was performed according to the USP Type II paddle method at 100 rpm in 500 mL of 0.001N HCl dissolution medium (without CTAB) maintained at 37° C.±0.5° C. Release profiles are shown in Figures 6 and 7, with the release profiles of formulations 1, 2, 3, and 4 shown in Figure 6 and the release profiles of formulations 5, 6, 7, 8, and 9 shown in Figure 7. The release profiles of formulations 10, 11, 12, 13, and 14 are shown in Figure 10. The release profiles of formulations 15, 16, and 17 are shown in Figure 11. As reported in the tables and figures below, all formulations released more than 40% of the enzalutamide in 10 minutes compared to XTANDI® capsules which released less than 10%.

[0162] [Table 7]

[0163] [Table 8]

[0164] In an in vivo study, 160 mg doses of enzalutamide formulations 1 and 2 as described above were administered to male beagle dogs, and plasma levels of enzalutamide were measured periodically over a 96-hour period. Figure 4 shows the mean plasma concentration-time profiles. As shown in the figure, formulation 1 exhibited a similar plasma concentration-time profile to an equivalent dose of XTANDI® capsules (four 40 mg capsules), while formulation 2, although with a similar curve, produced reduced plasma concentrations.

[0165] In addition, 160 mg doses of enzalutamide formulations 7, 8 and 9 as described above were administered to male beagle dogs and plasma levels of enzalutamide were measured periodically over a 144 hour period. Figure 5 shows the mean plasma concentration-time profiles. As shown in the figure, formulations 7, 8 and 9 showed plasma concentration-time profiles similar to the equivalent dose of XTANDI® capsules (four 40 mg capsules).

[0166] Example 2 The bitterness of the above-described formulations 1, 2, 7 and 9 was evaluated using the Insent taste recognition device TS-5000Z. The TS-5000Z device is equipped with multiple artificial lipid membranes with different properties designed to evaluate different taste modalities (bitter, salty, sour, astringent). The device measures the potential of the artificial lipid membrane surface of the device (affected by the test substance in contact with the membrane). For example, the test substance may change the potential by electrostatic interaction with the hydrophilic group of the lipid membrane, hydrophobic interaction with the hydrophobic group of the lipid membrane, etc. Thus, by measuring the change in the membrane potential, it is possible to detect taste modalities such as bitterness. In these experiments, the test sample was prepared as a 0.01% solution of the enzalutamide formulation in 10 mM KCl, and a bitter standard solution of 0.01 mM quinine hydrochloride was used.

[0167] As reported in the table below, formulations 1, 2, 7, 8 and 9 have no bitter taste compared to a standard bitter (quinine hydrochloride) solution. Formulation 8 exhibited a slight bitter aftertaste, formulations 1, 2 and 9 exhibited minimal bitter aftertaste, while formulation 7 exhibited no bitter aftertaste.

[0168] [Table 9]

[0169] Example 3 The stability of formulations 8, 10 and 17 as described in Example 1 was evaluated at 40° C. and 75% relative humidity for 1 month and 3 months. The results of this study are shown in the table below.

[0170] [Table 10]

[0171] The target impurity limits for each category were as follows: 0.2% w / w for dioxoimidazoline impurity; 0.2% w / w for the highest individual impurity; and 1.0% w / w for total impurities. These targets were achieved for formulations (with or without BHA and BHT) formulated with DL-methionine as the antioxidant. Results showed that formulations 10 and 17 were stable at 3 months, meeting the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines for impurity limits.

[0172] Example 4 A two-treatment, two-sequence randomized crossover study was conducted to compare the bioavailability of Formulation 10 as described in Table 3 at a dose of 160 mg with XTANDI® (enzalutamide) capsules (4 tablets x 400 mg) in 18 healthy adult males under fasting conditions. In each study period, a single dose of the enzalutamide composition was administered orally in the morning after a 10-hour overnight fast. Fasting conditions were maintained for up to 4 hours after dosing. Plasma concentrations of enzalutamide were quantified by serial blood sampling, and pharmacokinetic (PK) parameters were determined by noncompartmental analysis. Mean plasma concentration-time profiles are reported in Figure 12. Peak plasma concentrations (C max ), and the area under the plasma concentration-time curve up to 72 hours (AUC 0-72h ), and time to peak plasma concentration (T max ) are shown in the table below. AUC values ​​were calculated by the Linear-up and Log-down Trapezoidal Method. The results showed that Formulation 10 was comparable to XTANDI®.

Claims

1. 1. An oral liquid pharmaceutical composition of enzalutamide, comprising: (i) about 2.5% to about 6% w / w of enzalutamide; (ii) optionally, from about 0.5% to about 25% w / w of an oil selected from one or more of vegetable oils, flavor oils, and essential oils; (iii) from about 5% to about 85% w / w of a surfactant and / or solubilizer, wherein the surfactant comprises one or more selected from tocopherol succinate polyethylene glycol surfactants, polyoxyethylene castor oil surfactants, polyoxyl hydrogenated castor oil surfactants, polyoxyl hydroxystearic acid surfactants, lauroyl polyoxyl glyceride surfactants, stearoyl polyoxyl glyceride surfactants, and polyoxyl stearate surfactants, and the solubilizer comprises one or more selected from polyethylene glycol caprylic / capric acid glyceride solubilizers, polyglyceryl oleate solubilizers, and polyoxyethylene sorbitan monooleate solubilizers; (iv) from about 5% to about 25% w / w of a co-surfactant selected from one or more of propylene glycol monolaurate Type II surfactants, oleoyl polyoxyl-6-glyceride surfactants, linoleoyl polyoxylglyceride surfactants, lauroyl polyoxylglyceride surfactants, glycerol monocaprylocaprate Type I surfactants, and propylene glycol monocaprylate Type II surfactants; (v) from about 0.01% to about 1% w / w of an antioxidant comprising one or more selected from DL-methionine, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), arginine, cysteine, ascorbic palmitate, sodium metabisulfite, sodium thiosulfate, propyl gallate, gamma linolenic acid, ethylenediaminetetraacetic acid (EDTA), ascorbic acid, and alpha tocopherol; (vi) optionally, from about 0.5% to about 5% w / w of a precipitation retardant selected from one or more of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer solubilizers, polyoxyethylene polyoxypropylene glycol solubilizers, polyvinyl pyrrolidone solubilizers, vinyl pyrrolidone-vinyl acetate copolymer solubilizers, polyvinyl alcohol / polyethylene glycol graft copolymer solubilizers, hydroxypropyl methylcellulose solubilizers, and hypromellose acetate succinate solubilizers; and (vii) A composition optionally comprising about 1% to about 5% w / w water.

2. 1. An oral liquid pharmaceutical composition of enzalutamide, comprising: (i) about 2.5% to about 6% w / w of enzalutamide; (ii) optionally, from about 0.5% to about 25% w / w of an oil selected from one or more of vegetable oils, flavor oils, and essential oils; (iii) from about 5% to about 65% w / w of a surfactant comprising one or more selected from tocopherol succinate polyethylene glycol surfactants, polyoxyethylene castor oil surfactants, polyoxyl hydrogenated castor oil surfactants, polyoxyl hydroxystearic acid surfactants, lauroyl polyoxyl glyceride surfactants, stearoyl polyoxyl glyceride surfactants, and polyoxyl stearate surfactants; (iv) from about 5% to about 30% w / w of a co-surfactant selected from one or more of propylene glycol monolaurate Type II surfactants, oleoyl polyoxyl-6-glyceride surfactants, linoleoyl polyoxylglyceride surfactants, lauroyl polyoxylglyceride surfactants, glycerol monocaprylocaprate Type I surfactants, and propylene glycol monocaprylate Type II surfactants; (v) from about 0.01% to about 1% w / w of an antioxidant comprising one or more selected from DL-methionine, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), arginine, cysteine, ascorbic palmitate, sodium metabisulfite, sodium thiosulfate, propyl gallate, gamma linolenic acid, ethylenediaminetetraacetic acid (EDTA), ascorbic acid, and alpha tocopherol; (vi) optionally, from about 0.5% to about 5% w / w of a precipitation retardant selected from one or more of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer solubilizers, polyoxyethylene polyoxypropylene glycol solubilizers, polyvinyl pyrrolidone solubilizers, vinyl pyrrolidone-vinyl acetate copolymer solubilizers, polyvinyl alcohol / polyethylene glycol graft copolymer solubilizers, hydroxypropyl methylcellulose solubilizers, and hypromellose acetate succinate solubilizers; and (vii) A composition optionally comprising about 1% to about 5% w / w water.

3. The composition of claim 1, comprising about 20 to about 45 mg of enzalutamide per mL of the composition, or about 160 mg of enzalutamide per 3.5 to 6.0 mL of the composition.

4. The composition described in claim 2, comprising approximately 20 to approximately 45 mg of enzalutamide per 1 mL of the composition, or approximately 160 mg of enzalutamide per 3.5 to 6.0 mL of the composition.

5. 5. The composition of any one of claims 1 to 4, comprising: (a) from about 0.5% to about 20% w / w of said oil, optionally comprising from about 0.5% to about 5% w / w of said flavor oil or said essential oil and from about 3% to about 15% w / w of said vegetable oil; (b) from about 5% to about 50% w / w of said surfactant; (c) from about 5% to about 20% w / w of said co-surfactant; and (d) from about 0.5% to about 1% w / w of said precipitation retardant.

6. 5. The composition of any one of claims 1 to 4, wherein the surfactant comprises a tocopherol succinate polyethylene glycol surfactant and a polyoxyethylene castor oil surfactant, optionally wherein the tocopherol succinate polyethylene glycol surfactant is Vitamin E TPGS and the polyoxyethylene castor oil surfactant is PEG 35 castor oil.

7. 5. The composition of claim 1, wherein the co-surfactant comprises a propylene glycol monolaurate Type II surfactant, an oleoyl polyoxyl-6-glyceride surfactant, a glycerol monocaprylocarate Type I surfactant, or a propylene glycol monocaprylate Type II surfactant, and optionally the propylene glycol monolaurate Type II surfactant is CAPMUL® PG-12, the oleoyl polyoxyl-6-glyceride surfactant is LABRAFIL® M 1944 CS, the glycerol monocaprylocarate Type I surfactant is CAPMUL® MCM, and the propylene glycol monocaprylate Type II surfactant is CAPMUL® PG-8.

8. 5. The composition of claim 1, further comprising about 10% to about 35% w / w of a co-solvent, wherein the co-solvent comprises one or more selected from diethylene glycol monoethyl ether, glycofurol, and N-methylpyrrolidone.

9. 5. The composition of any one of claims 1 to 4, comprising or further comprising about 10% to about 65% w / w of a solubilizing agent, wherein the solubilizing agent comprises one or more selected from polyethylene glycol caprylic / capric glyceride solubilizing agents, polyglyceryl oleate solubilizing agents, and polyoxyethylene sorbitan monooleate solubilizing agents.

10. 5. The composition of claim 1, wherein the antioxidant comprises one or more selected from DL-methionine, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), arginine, and cysteine.

11. The composition according to any one of claims 1 to 4, further comprising one or more of a sweetening agent and a flavoring agent.

12. 12. The composition of claim 11, wherein the sweetening agent comprises one or more selected from sucralose, ammonium glycyrrhizinate, saccharin, aspartame, acesulfame potassium, cyclamate, erythritol, and neotame, and the flavoring agent comprises one or more selected from vanilla flavor, banana flavor, grapefruit flavor, strawberry flavor, raspberry flavor, bubblegum flavor, and caramel flavor.

13. the oils are present and include peppermint oil as a flavor oil and corn oil as a vegetable oil; the surfactant is a tocopherol succinate polyethylene glycol surfactant or a combination of a tocopherol succinate polyethylene glycol surfactant and a polyoxyethylene castor oil surfactant, optionally wherein the surfactant is Vitamin E TPGS or wherein the surfactant is Vitamin E TPGS and PEG 35 castor oil; the co-surfactant is a propylene glycol monolaurate Type II co-surfactant, an oleoyl polyoxyl-6-glyceride co-surfactant, a glycerol monocaprylocarate Type I co-surfactant, or a propylene glycol monocaprylate Type II co-surfactant; and the precipitation inhibitor is present and is a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; The composition according to any one of claims 1 to 4.

14. (i) about 2.5% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 10% w / w vegetable oil; (iv) about 7% w / w of said propylene glycol monolaurate Type II co-surfactant; (v) about 15% w / w of said tocopherol succinate polyethylene glycol surfactant; (vi) about 60% w / w of said polyethylene glycol caprylic / capric glyceride solubilizer; (vii) about 0.5% w / w of said polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) the antioxidant; (ix) optionally the sweetening agent; (x) optionally containing said flavoring agent; and (xi) water is present in an amount of about 1.5% w / w; The composition according to any one of claims 1 to 4.

15. the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monolaurate Type II co-surfactant is CAPMUL® PG-12; the tocopherol polyethylene glycol succinate surfactant is a D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor is SOLUPLUS®; The antioxidant comprises one or more selected from DL-methionine, butylated hydroxyanisole (BHA), and butylated hydroxytoluene; the sweetening agent is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agents are present and include vanilla and banana; 15. The composition of claim 14.

16. (i) about 2.5% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 10% w / w vegetable oil; (iv) about 7% w / w of said propylene glycol monolaurate Type II co-surfactant; (v) about 15% w / w of said tocopherol succinate polyethylene glycol surfactant; (vi) about 60% w / w of said polyethylene glycol caprylic / capric glyceride solubilizer; (vii) about 0.5% w / w of said polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) the antioxidant; (ix) optionally the sweetening agent; (x) optionally containing said flavoring agent; and (xi) water is present in an amount of about 3% w / w; The composition according to any one of claims 1 to 4.

17. the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monolaurate Type II co-surfactant is CAPMUL® PG-12; the tocopherol polyethylene glycol succinate surfactant is a D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor is SOLUPLUS®; the antioxidant comprises DL-methionine; the sweetening agent is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agents are present and include vanilla and banana; 17. The composition of claim 16.

18. (i) about 2.5% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 10% w / w vegetable oil; (iv) about 7% w / w of said propylene glycol monolaurate Type II co-surfactant; (v) about 15% w / w of said tocopherol succinate polyethylene glycol surfactant; (vi) about 60% w / w of said polyethylene glycol caprylic / capric glyceride solubilizer; (vii) about 0.5% w / w of said polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) the antioxidant; (ix) optionally the sweetening agent; (x) optionally containing said flavoring agent; and (xi) water is present in an amount of about 1.5% w / w; The composition according to any one of claims 1 to 4.

19. the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monolaurate Type II co-surfactant is CAPMUL® PG-12; the tocopherol polyethylene glycol succinate surfactant is a D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor is SOLUPLUS®; the antioxidant comprises DL-methionine; the sweetening agent is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agents are present and include vanilla and banana; 19. The composition of claim 18.

20. (i) about 2.5% w / w enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 10% w / w vegetable oil; (iv) about 7% w / w of said propylene glycol monolaurate Type II co-surfactant; (v) about 15% w / w of said tocopherol succinate polyethylene glycol surfactant; (vi) about 60% w / w of said polyethylene glycol caprylic / capric glyceride solubilizer; (vii) the antioxidant; (viii) optionally the sweetening agent; (ix) optionally containing said flavoring agent; and (x) water is present in an amount of about 3% w / w; The composition according to any one of claims 1 to 4.

21. the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monolaurate Type II co-surfactant is CAPMUL® PG-12; the tocopherol polyethylene glycol succinate surfactant is a D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the antioxidant comprises DL-methionine; the sweetening agent is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agents are present and include vanilla and banana; 21. The composition of claim 20.

22. (i) about 2.5% w / w enzalutamide; (ii) about 7% w / w of said propylene glycol monolaurate Type II co-surfactant; (iii) about 15% w / w of said tocopherol succinate polyethylene glycol surfactant; (iv) about 60% w / w of said polyethylene glycol caprylic / capric glyceride solubilizer; (v) about 0.5% w / w of said polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (vi) the antioxidant; (vii) optionally the sweetening agent; (viii) optionally containing said flavoring agent; and (ix) water is present in an amount of about 3% w / w; The composition according to any one of claims 1 to 4.

23. the propylene glycol monolaurate Type II co-surfactant is CAPMUL® PG-12; the tocopherol polyethylene glycol succinate surfactant is a D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor is SOLUPLUS®; the antioxidant comprises DL-methionine; the sweetening agent is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agents are present and include vanilla and banana; 23. The composition of claim 22.

24. the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monolaurate Type II co-surfactant is CAPMUL® PG-12; the tocopherol polyethylene glycol succinate surfactant is a D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor is SOLUPLUS®; the antioxidant comprises arginine; the sweetening agent is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agents are present and include vanilla and banana; 17. The composition of claim 16.

25. the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monolaurate Type II co-surfactant is CAPMUL® PG-12; the tocopherol polyethylene glycol succinate surfactant is a D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor is SOLUPLUS®; the antioxidant comprises cysteine; the sweetening agent is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agents are present and include vanilla and banana; 17. The composition of claim 16.

26. (i) about 3% w / w of enzalutamide; (ii) about 1.0% w / w flavor oil; (iii) about 3.5% w / w vegetable oil; (iv) about 13% w / w of said oleoyl polyoxyl-6-glyceride co-surfactant; (v) about 12% w / w of said tocopherol succinate polyethylene glycol surfactant; (vi) about 20% w / w of said diethylene glycol monoethyl ether co-solvent; (vii) about 26% w / w of said polyethylene glycol caprylic / capric glyceride solubilizer; (viii) about 0.75% w / w of said polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (ix) about 21% w / w of said polyoxyethylene castor oil surfactant; (x) the antioxidant; (xi) optionally the sweetening agent; and (xii) optionally containing said flavoring agent; The composition according to any one of claims 1 to 4.

27. the flavor oil is peppermint oil; the vegetable oil is corn oil; the oleoyl polyoxyl-6-glyceride co-surfactant is LABRAFIL® M 1944 CS; the tocopherol succinate polyethylene glycol surfactant is Vitamin E TPGS; the diethylene glycol monoethyl ether co-solvent is TRANSCUTOL® HP; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor is SOLUPLUS®; the polyoxyethylene castor oil surfactant is KOLLIPHOR® ELP; The antioxidant comprises one or more selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT); the sweetening agent is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla; 27. The composition of claim 26.

28. (i) about 4% w / w enzalutamide; (ii) about 1.5% w / w of flavor oil; (iii) about 5% w / w vegetable oil; (iv) about 17% w / w of said oleoyl polyoxyl-6-glyceride co-surfactant; (v) about 6% w / w of said tocopherol succinate polyethylene glycol surfactant; (vi) about 25% w / w of said diethylene glycol monoethyl ether co-solvent; (vii) about 40% w / w of said polyethylene glycol caprylic / capric glyceride solubilizer; (viii) about 0.5% w / w of said polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (ix) the antioxidant; (x) optionally the sweetening agent; and (xi) optionally comprising said flavoring agent; The composition according to any one of claims 1 to 4.

29. the flavor oil is peppermint oil; the vegetable oil is corn oil; the oleoyl polyoxyl-6-glyceride co-surfactant is LABRAFIL® M 1944 CS; the tocopherol polyethylene glycol succinate surfactant is a D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the diethylene glycol monoethyl ether co-solvent is TRANSCUTOL® HP; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor is SOLUPLUS®; The antioxidant comprises one or more selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT); the sweetening agent is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla; 29. The composition of claim 28.

30. (i) about 3% w / w of enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 12% w / w vegetable oil; (iv) about 13% w / w of said oleoyl polyoxyl-6-glyceride co-surfactant; (v) about 18% w / w of said tocopherol succinate polyethylene glycol surfactant; (vi) about 20% w / w of said diethylene glycol monoethyl ether co-solvent; (vii) about 0.75% w / w of said polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) about 30% w / w of said polyoxyethylene castor oil surfactant; (ix) the antioxidant; (x) optionally the sweetening agent; and (xi) optionally comprising said flavoring agent; The composition according to any one of claims 1 to 4.

31. the flavor oil is peppermint oil; the vegetable oil is corn oil; the oleoyl polyoxyl-6-glyceride co-surfactant is LABRAFIL® M 1944 CS; the tocopherol succinate polyethylene glycol surfactant is Vitamin E TPGS; the diethylene glycol monoethyl ether co-solvent is TRANSCUTOL® HP; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor is SOLUPLUS®; the polyoxyethylene castor oil surfactant is KOLLIPHOR® ELP; The antioxidant comprises one or more selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT); the sweetening agent is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla; 31. The composition of claim 30.

32. (i) about 3% w / w of enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 11% w / w vegetable oil; (iv) about 7% w / w of said glycerol monocaprylocapriate Type I co-surfactant; (v) about 17% w / w of said tocopherol succinate polyethylene glycol surfactant; (vi) about 55% w / w of said polyethylene glycol caprylic / capric glyceride solubilizer; (vii) about 0.5% w / w of said polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) the antioxidant; (ix) optionally the sweetener; and (x) optionally containing said flavoring agent; The composition according to any one of claims 1 to 4.

33. the flavor oil is peppermint oil; the vegetable oil is corn oil; the glycerol monocaprylocarate Type I co-surfactant is CAPMUL® MCM; the tocopherol polyethylene glycol succinate surfactant is a D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor is SOLUPLUS®; The antioxidant comprises one or more selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT); the sweetening agent is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla; 33. The composition of claim 32.

34. (i) about 3% w / w of enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 11% w / w vegetable oil; (iv) about 7% w / w of said propylene glycol monocaprylate Type II co-surfactant; (v) about 17% w / w of said tocopherol succinate polyethylene glycol surfactant; (vi) about 55% w / w of said polyethylene glycol caprylic / capric glyceride solubilizer; (vii) about 0.5% w / w of said polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) the antioxidant; (ix) optionally the sweetener; and (x) optionally containing said flavoring agent; The composition according to any one of claims 1 to 4.

35. the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monocaprylate Type II co-surfactant is CAPMUL® PG-8; the tocopherol polyethylene glycol succinate surfactant is a D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor is SOLUPLUS®; The antioxidant comprises one or more selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT); the sweetening agent is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla; 35. The composition of claim 34.

36. (i) about 3% w / w of enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 11% w / w vegetable oil; (iv) about 7% w / w of said propylene glycol monolaurate Type II co-surfactant; (v) about 17% w / w of said tocopherol succinate polyethylene glycol surfactant; (vi) about 55% w / w of said polyethylene glycol caprylic / capric glyceride solubilizer; (vii) about 0.5% w / w of said polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) the antioxidant; (ix) optionally the sweetener; and (x) optionally containing said flavoring agent; The composition according to any one of claims 1 to 4.

37. the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monolaurate Type II co-surfactant is CAPMUL® PG-12; the tocopherol polyethylene glycol succinate surfactant is a D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor is SOLUPLUS®; The antioxidant comprises one or more selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT); the sweetening agent is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla; 37. The composition of claim 36.

38. (i) about 3% w / w of enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 12% w / w vegetable oil; (iv) about 15% w / w of said oleoyl polyoxyl-6-glyceride co-surfactant; (v) about 17% w / w of said tocopherol succinate polyethylene glycol surfactant; (vi) about 19% w / w of said diethylene glycol monoethyl ether co-solvent; (vii) about 0.75% w / w of said polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) about 28% w / w of said polyoxyethylene castor oil surfactant; (ix) the antioxidant; (x) optionally the sweetening agent; and (xi) optionally comprising said flavoring agent; The composition according to any one of claims 1 to 4.

39. the flavor oil is peppermint oil; the vegetable oil is corn oil; the oleoyl polyoxyl-6-glyceride co-surfactant is LABRAFIL® M 1944 CS; the tocopherol succinate polyethylene glycol surfactant is Vitamin E TPGS; the diethylene glycol monoethyl ether co-solvent is TRANSCUTOL® HP; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor is SOLUPLUS®; the polyoxyethylene castor oil surfactant is KOLLIPHOR® ELP; The antioxidant comprises one or more selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT); the sweetening agent is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla; 39. The composition of claim 38.

40. (i) about 3% w / w of enzalutamide; (ii) about 5% w / w of flavor oil; (iii) about 10% w / w vegetable oil; (iv) about 7% w / w of said propylene glycol monolaurate Type II co-surfactant; (v) about 15% w / w of said tocopherol succinate polyethylene glycol surfactant; (vi) about 60% w / w of said polyethylene glycol caprylic / capric glyceride solubilizer; (vii) about 0.5% w / w of said polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor; (viii) the antioxidant; (ix) optionally the sweetener; and (x) optionally containing said flavoring agent; The composition according to any one of claims 1 to 4.

41. 41. The composition of claim 40, the flavor oil is peppermint oil; the vegetable oil is corn oil; the propylene glycol monolaurate Type II co-surfactant is CAPMUL® PG-12; the tocopherol polyethylene glycol succinate surfactant is a D-α-tocopherol polyethylene glycol 1000 succinate surfactant; the polyethylene glycol caprylic / capric glyceride solubilizer is ACCONON® MC8-2; the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer precipitation inhibitor is SOLUPLUS®; The antioxidant comprises one or more selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT); the sweetening agent is present and comprises one or more selected from sucralose and ammonium glycyrrhizinate; and the flavoring agent is present and comprises vanilla; 41. The composition of claim 40.

42. 1. An oral liquid pharmaceutical composition of enzalutamide, comprising: (i) about 160 mg of enzalutamide in a volume of about 2.5 to 6.0 mL; (ii) about 0.5% to about 25% w / w of an oil selected from one or more of vegetable oils, flavor oils, and essential oils; (iii) from about 5% to about 55% w / w of a surfactant comprising one or more selected from tocopherol succinate polyethylene glycol surfactants, polyoxyethylene castor oil surfactants, polyoxyl hydrogenated castor oil surfactants, polyoxyl hydroxystearic acid surfactants, lauroyl polyoxyl glyceride surfactants, stearoyl polyoxyl glyceride surfactants, and polyoxyl stearate surfactants; (iv) from about 5% to about 25% w / w of a co-surfactant selected from one or more of oleoyl polyoxyl-6-glyceride surfactants, linoleoyl polyoxylglyceride surfactants, lauroyl polyoxylglyceride surfactants, glycerol monocaprylocarate Type I surfactants, propylene glycol monocaprylate Type II surfactants, and propylene glycol monolaurate Type II surfactants; and (v) A composition comprising from about 0.5% to about 5% w / w of a precipitation retardant selected from one or more of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer solubilizer, a polyoxyethylene polyoxypropylene glycol solubilizer, a polyvinyl pyrrolidone solubilizer, a vinyl pyrrolidone-vinyl acetate copolymer solubilizer, a polyvinyl alcohol / polyethylene glycol graft copolymer solubilizer, a hydroxypropyl methylcellulose solubilizer, and a hypromellose acetate succinate solubilizer.

43. 1. An oral liquid pharmaceutical composition of enzalutamide, comprising: (i) about 3% to about 6% w / w of enzalutamide; (ii) about 0.5% to about 25% w / w of an oil selected from one or more of vegetable oils, flavor oils, and essential oils; (iii) from about 5% to about 55% w / w of a surfactant comprising one or more selected from tocopherol succinate polyethylene glycol surfactants, polyoxyethylene castor oil surfactants, polyoxyl hydrogenated castor oil surfactants, polyoxyl hydroxystearic acid surfactants, lauroyl polyoxyl glyceride surfactants, stearoyl polyoxyl glyceride surfactants, and polyoxyl stearate surfactants; (iv) from about 5% to about 25% w / w of a co-surfactant selected from one or more of oleoyl polyoxyl-6-glyceride surfactants, linoleoyl polyoxylglyceride surfactants, lauroyl polyoxylglyceride surfactants, glycerol monocaprylocarate Type I surfactants, propylene glycol monocaprylate Type II surfactants, and propylene glycol monolaurate Type II surfactants; and (v) A composition comprising from about 0.5% to about 5% w / w of a precipitation retardant selected from one or more of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer solubilizer, a polyoxyethylene polyoxypropylene glycol solubilizer, a polyvinyl pyrrolidone solubilizer, a vinyl pyrrolidone-vinyl acetate copolymer solubilizer, a polyvinyl alcohol / polyethylene glycol graft copolymer solubilizer, a hydroxypropyl methylcellulose solubilizer, and a hypromellose acetate succinate solubilizer.

44. 44. The composition of any one of claims 1 to 4 and 42 to 43, packaged as a unit dose containing 160 mg of enzalutamide.

45. the composition is free of caprylocaproyl polyoxyl-8 glyceride solubilizers / surfactants, optionally the excluded caprylocaproyl polyoxyl-8 glyceride solubilizers / surfactants are LABRASOL® and / or LABRASOL® ALF, optionally the composition is free of LABRASOL® and free of LABRASOL® ALF; the composition does not comprise polyethylene glycol, optionally wherein the excluded polyethylene glycol is polyethylene glycol 300 (PEG300) and / or polyethylene glycol 400 (PEG400), optionally wherein the composition does not comprise PEG300 and does not comprise PEG400; the composition does not contain propylene glycol; or the composition is ethanol-free; The composition according to any one of claims 1 to 4 and 42 to 43.

46. 44. The oral liquid pharmaceutical composition according to any one of claims 1 to 4 and 42 to 43, for use in treating prostate cancer.

47. Use of enzalutamide in the preparation of a medicament for treating prostate cancer, wherein the medicament comprises an oral liquid pharmaceutical composition described in any one of claims 1 to 4 and 42 to 43.

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