Pharmaceutical composition comprising enzalutamide
The present invention relates to a tablet composition comprising a granulate consisting of a co-precipitate on a substrate, wherein the co-precipitate comprises enzalutamide in amorphous form and a cellulosic concentration enhancing polymer. The invention further relates to the use of said composition as a medicament, particularly in the treatment of castration-resistant prostate cancer.
1 . A tablet composition comprising a granulate consisting of a co-precipitate on a substrate, wherein the co-precipitate comprises enzalutamide in amorphous form and a cellulosic concentration enhancing polymer;
wherein said granulate was obtained by spraying a solution comprising the enzalutamide and the cellulosic concentration enhancing polymer over the substrate and subsequently drying to obtain said co-precipitate on the substrate;
wherein said cellulosic concentration enhancing polymer is selected from hydroxylpropylmethylcellulose acetate succinate (HPMCAS) and hydroxypropylmethylcellulose phthalate (HPMCP);
wherein the substrate comprises a sugar alcohol, microcrystalline cellulose, or mixtures thereof.
2 . The tablet composition according to claim 1 , wherein a weight ratio of enzalutamide to the cellulosic concentration enhancing polymer ranges from 1:2 to 1:6.
3 . The tablet composition according to claim 1 , wherein the sugar alcohol is mannitol.
4 . The tablet composition according to claim 1 , wherein the substrate further comprises a disintegrant.
5 . The tablet composition according to claim 4 , wherein the disintegrant is croscarmellose sodium.
6 . The tablet composition according to claim 1 , wherein the co-precipitate further comprises a surfactant.
7 . The tablet composition according to claim 6 , wherein the surfactant is a poloxamer.
8 . The tablet composition according to claim 1 , further comprising pharmaceutically acceptable excipients.
9 . The tablet composition according to claim 8 , wherein the pharmaceutically acceptable excipients are selected from one or more diluents, disintegrants, glidants or lubricants.
10 . The tablet composition according to claim 1 , wherein the composition exhibits a dissolution rate of less than 15% in 30 minutes when tested in 300 ml 0.03 N hydrochloric acid pH 1.2 and at least 75% in 90 minutes when tested in 900 ml phosphate buffer pH 6.8 in a USP apparatus II at 50 rpm (normal vessel), 37° C.
11 . A process to prepare the tablet composition according to claim 1 , comprising the following steps:
a) dissolving enzalutamide, the cellulosic concentration enhancing polymer and optionally a surfactant in a solvent system comprising acetone to form the solution;
b) spraying the solution over the substrate;
c) drying the obtained granulate;
d) blending with further pharmaceutically acceptable excipients;
e) compressing into tablets;
f) optionally coating of the tablets.
12 . The process according to claim 11 , wherein step b) is executed in a fluid bed granulator.
13 . The process according to claim 11 , further comprising the step of dry granulation after step c).
14 . A method for treating castration-resistant prostate cancer, which comprises administering the tablet composition according to claim 1 to a patient that has castration-resistant prostate cancer.
15 . The method according to claim 14 , wherein said tablet contains 80 mg of said enzalutamide.