Pharmaceutical composition comprising an androgen receptor inhibitor

Abstract

The present invention relates to the oral pharmaceutical composition comprising an androgen receptor inhibitor and one or more pharmaceutically acceptable excipients selected from the group comprising of fillers/vehicles, solvents/co-solvents, preservatives/antioxidants, surfactants, buffering agents, chelating agents, sweetening agents, flavouring agents, sweetness/flavour enhancing agents, or combinations thereof. The present invention also relates to the processes for the preparation of the oral pharmaceutical composition comprising androgen receptor inhibitor and one or more pharmaceutically acceptable excipients.

1 . A liquid oral dosage form comprising an androgen receptor inhibitor and one or more pharmaceutically acceptable excipients. 
     
     
         2 . The liquid oral dosage form according to  claim 1 , wherein one or more pharmaceutically acceptable excipients are selected from the group consisting of fillers/vehicles, solvents/co-solvents, preservatives, antioxidants, surfactants, buffering agents, chelating agents, sweetening agents, flavouring agents, sweetness/flavour enhancing agents, or combinations thereof. 
     
     
         3 . The liquid oral dosage form according to  claim 1 , wherein the androgen receptor inhibitor is selected from the group consisting of Enzalutamide, Bicalutamide, Flutamide, Nilutamide, (R)-Bicalutamide, Topilutamide, Apalutamide (ARN-509, JNJ-56021927), Darolutamide (ODM-201, BAY-1841788), Prnxalutamide (GT-0918), Saviteronel (VT-464) 1,1-dichloro-2,2-bis (4-chlorophenyl) ethane, PF-998425, Abiraterone acetate, Cabazitaxel, Degarelix, Docetaxel, Goserelin acetate, Leuprolide acetate, Mitoxanlrone hydrochloride, Sipuleucel-T, and Radium 223 dichloride. 
     
     
         4 . The liquid oral dosage form according to  claim 2 , wherein one or more filler or vehicle is selected from the group consisting of purified water, hydro-alcoholic, polyhydric alcohols and buffers, vegetable oils, mineral oils, organic oily bases or emulsified bases, and triglycerides. 
     
     
         5 . The liquid oral dosage form according to  claim 2 , wherein one or more solvent or co-solvent is selected from the group consisting of water, ethanol, polyethylene glycols (PEG), sorbitol, glycerin, propylene glycol and benzyl alcohol. 
     
     
         6 . The liquid oral dosage form according to  claim 2 , wherein one or more buffering agent is selected from the group consisting of Sodium acetate, Sodium citrate, Ammonium sulfate, Sodium phosphate, Disodium hydrogen phosphate, Potassium citrate, Citric acid monohydrate, and Trisodium citrate dihydrate. 
     
     
         7 . The liquid oral dosage form according to  claim 2 , wherein one or more antioxidants selected from the group consisting of butylatedhydroxyanisole (BHA), butylatedhydroxy toluene (BHT), sodium metabisulfite, ascorbic acid, alpha tocopherol and sodium edetate. 
     
     
         8 . The liquid oral dosage form according to  claim 2 , wherein one or more chelating agent is selected from the group consisting of citric acid monohydrate, disodium edetate, dipotassiumedetate, edetic acid, fumaric acid, malic acid, phosphoric acid, sodium edetate, tartaric acid and trisodiumedetate. 
     
     
         9 . The liquid oral dosage form according to  claim 2 , wherein one or more preservative is selected from the group consisting of Benzyl alcohol, Chloro-butanol, Chloro-cresol, Alkyl esters of Paraben, Phenol, Phenyl ethanol, Benzoic acid, Potassium sorbale, Sodium benzoate, propylene glycol and chloroform. 
     
     
         10 . The liquid oral dosage form according to  claim 2 , wherein one or more sweetening agent is selected from the group consisting of sucralose, sucrose, acesulfame potassium, liquid glucose, glycerine, sorbitol, liquid maltitol, saccharin sodium and aspartame. 
     
     
         11 . The liquid oral dosage form according to  claim 2 , wherein one or more flavouring agent is selected from the group consisting of essential oils and fruit flavours, wherein essential oil is selected from the group consisting of peppermint oil, orange oil, and lemon oil and fruit flavour is selected from the group comprising of mint/peppermint flavour, raspberry flavour, strawberry flavour and tutti-fruity flavour. 
     
     
         12 . The liquid oral dosage form according to  claim 2 , wherein one or more surfactant is selected from the group consisting of polyoxyethylensorbitan fatty acid esters (Tween), polyoxyethylene alkyl ethers (e.g. Brij), alkylphenylpolyoxyethylene ethers (e.g. Triton-X), polyoxyethylene-polyoxypropylene copolymer (e.g. Poloxamer, Pluronic), sodium dodecyl sulphate (SDS), Labrasol, Labrasol ALF, PEG 300, PEG 400 and a combination thereof. 
     
     
         13 . A liquid oral dosage form comprising Enzalutamide having particle size D90 less than 20 microns and one or more pharmaceutically acceptable excipients, wherein the one or more pharmaceutically acceptable excipients are selected from the group consisting of a surfactant consisting of Labrasol/Labrasol ALF, an antioxidant consisting of BHA and BHT, a solvent consisting of ethanol, a sweetening agent consisting of sucralose, a flavouring agent consisting of mint flavour and a filler/vehicle consisting of medium chain triglyceride. 
     
     
         14 . A process for the preparation of a liquid oral dosage form according to  claim 1 , wherein the process comprises steps of:
 (a) Mix one or more surfactants and one or more solvents;   (b) Dissolve androgen receptor inhibitor in the mixture obtained in Step (a);   (c) Add one or more sweetening agents in the mixture obtained in Step (b);   (d) Add one or more antioxidants in the mixture obtained in Step (c);   (e) Dilute the obtained mixture in Step (d) up to the desired volume with one or more filler/vehicle; and   (f) Add one or more flavouring agents in the final composition obtained in Step (e),   OR   (a) Dissolve the required quantity of one or more surfactants in the one more solvents;   (b) Add required quantity of one or more antioxidants in the solution obtained in Step (a);   (c) Add androgen receptor inhibitor into the solution obtained in Step (b);   (d) Add required quantity of one or more sweetening agent and one or more flavouring agent into the mixture obtained in Step (c); and   (e) Made up the final volume to desired quantity with one or more filler/vehicle.