Formulations of enzalutamide

Abstract

This disclosure provides formulations of enzalutamide and their use for treating hyperproliferative disorders.

1 - 4 . (canceled) 
     
     
         5 . A pharmaceutical composition comprising amorphous enzalutamide. 
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein at least about 80 wt % of the total amount of enzalutamide present is in an amorphous form. 
     
     
         7 . The pharmaceutical composition of  claim 5 , further comprising a concentration enhancing polymer. 
     
     
         8 . The pharmaceutical composition of  claim 7 , that when administered to an aqueous use environment, provides a maximum dissolved concentration of enzalutamide in the use environment that is at least 5-fold that provided by a control composition consisting essentially of an equivalent quantity of the enzalutamide in crystalline form alone. 
     
     
         9 - 12 . (canceled) 
     
     
         13 . The pharmaceutical composition of  claim 7 , wherein at least about 80 wt % of the total amount of enzalutamide present is in an amorphous form. 
     
     
         14 . The pharmaceutical composition of  claim 7 , wherein the concentration enhancing polymer is selected from the group consisting of an ionizable cellulosic polymer, a nonionizable cellulosic polymer, and a noncellulosic polymer. 
     
     
         15 . The pharmaceutical composition of  claim 14 , wherein the concentration enhancing polymer is the ionizable cellulosic polymer and the ionizable cellulosic polymer is selected from the group consisting of hydroxypropyl methyl cellulose acetate succinate, carboxymethyl ethyl cellulose, cellulose acetate phthalate, hydroxypropyl methyl cellulose phthalate, methyl cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropyl cellulose acetate phthalate, hydroxypropyl methyl cellulose acetate phthalate, cellulose acetate terephthalate, and cellulose acetate isophthalate. 
     
     
         16 . The pharmaceutical composition of  claim 14 , wherein the concentration enhancing polymer is the nonionizable cellulosic polymer and the nonionizable cellulosic polymer is elected from the group consisting of hydroxypropyl methyl cellulose acetate, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, methyl cellulose, hydroxyethyl methyl cellulose, hydroxyethyl cellulose acetate, and hydroxyethyl ethyl cellulose. 
     
     
         17 . The pharmaceutical composition of  claim 14 , wherein the concentration enhancing polymer is the noncellulosic polymer and the noncellulosic polymer is selected from the group consisting of carboxylic acid functionalized polymethacrylates; carboxylic acid functionalized polyacrylates; amine-functionalized polyacrylates; amine-functionalized polymethacrylates; proteins; carboxylic acid functionalized starches; vinyl polymers and copolymers having at least one substituent selected from the group consisting of hydroxyl, alkylacyloxy, and cyclicamido; vinyl copolymers of at least one hydrophilic, hydroxyl-containing repeat unit and at least one hydrophobic, alkyl- or aryl-containing repeat unit; polyvinyl alcohols that have at least a portion of their repeat units in the unhydrolyzed form; polyvinyl alcohol polyvinyl acetate copolymers; polyethylene glycol polypropylene glycol copolymers; polyvinyl pyrrolidone; polyvinyl pyrrolidone polyvinyl acetate copolymers, also called PVP-VA; polyethylene polyvinyl alcohol copolymers; polyoxyethylene-polyoxypropylene block copolymers; and graft copolymers of polyethyleneglycol, polyvinylcaprolactam and polyvinylacetate. 
     
     
         18 . (canceled) 
     
     
         19 . The pharmaceutical composition of  claim 7 , wherein the composition is in the form of a solid amorphous dispersion of enzalutamide and a concentration-enhancing polymer. 
     
     
         20 - 25 . (canceled) 
     
     
         26 . The pharmaceutical composition of  claim 19 , wherein at least about 80 wt % of the total amount of enzalutamide present is in an amorphous form. 
     
     
         27 . The pharmaceutical composition of  claim 19 , wherein the concentration-enhancing polymer is selected from the group consisting of hydroxypropylmethylcellulose acetate succinate (HPMCAS); hydroxypropylmethylcellulose (HPMC); hydroxypropylmethylcellulosephthalate (HPMCP); polyvinylpyrrolidonevinylacetate (PVP-VA); copolymers of methacrylic acid and methylmethacrylate in approximately a 1:1 ratio; and graft copolymers of polyethyleneglycol, polyvinylcaprolactam, and polyvinylacetate. 
     
     
         28 . The pharmaceutical composition of  claim 19 , comprising 60 wt % enzalutamide and hydroxypropylmethylcellulose acetate succinate. 
     
     
         29 . A tablet comprising 45-70 wt % of a solid amorphous dispersion of  claim 19 , the dispersion comprising 55-65 wt % enzalutamide and hydroxypropylmethylcellulose acetate succinate. 
     
     
         30 - 82 . (canceled) 
     
     
         83 . A pharmaceutical composition comprising a solid dispersion containing enzalutamide and a polymer. 
     
     
         84 . The pharmaceutical composition according to  claim 83 , wherein enzalutamide is an amorphous state. 
     
     
         85 . The pharmaceutical composition according to  claim 83 , wherein the polymer is a polymer or two or more polymers selected from the group consisting of polyvinyl pyrrolidone, polyethyleneoxide, poly(vinyl pyrrolidone-co-vinyl acetate), polymethacrylates, polyoxyethylene alkyl ethers, polyoxyethylene castor oils, polycaprolactam, polylactic acid, polyglycolic acid, poly(lactic-glycolic) acid, lipids, cellulose, pullulan, dextran, maltodextrin, hyaluronic acid, polysialic acid, chondroitin sulfate, heparin, fucoidan, pentosan polysulfate, spirulan, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, 10 carboxymethyl ethylcellulose, hydroxypropyl methylcellulose acetate succinate, cellulose acetate phthalate, cellulose acetate trimellitate, ethyl cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, and dextran polymer derivative. 
     
     
         86 . The pharmaceutical composition according to  claim 85 , wherein the polymer is hydroxypropyl methylcellulose acetate succinate. 
     
     
         87 . The pharmaceutical composition according to  claim 83 , wherein the amount of the polymer is 0.5 to 3 parts by weight, with respect to 1 part by weight of the enzalutamide. 
     
     
         88 . The pharmaceutical composition according to  claim 83 , wherein the amount of the polymer is 3 parts by weight, with respect to 1 part by weight of the enzalutamide. 
     
     
         89 - 93 . (canceled)