Formulations for cathepsin K inhibitors
View Patent ↗The instant invention relates to pharmaceutical compositions containing cathespin K inhibitors. Also disclosed are processes for making said pharmaceutical compositions.
1. A pharmaceutical composition comprising from 1% to 95% by weight of an amorphous cathepsin K inhibitor system and from 5% to 99% by weight of excipients comprising a diluent, a glidant, a lubricant, a surfactant and a disintegrant, wherein the amorphous cathepsin K inhibitor system comprises a cathepsin K inhibitor, which is N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide, and a polymer selected from the group consisting of HPMCAS, copovidone, cellulose acetate phthalate, cellulose acetate succinate, methylcellulose phthalate, ethylhydroxycellulose phthalate, polyvinylacetatephthalate, polyvinylbutyrate acetate, vinyl acetate-maleic anhydride copolymer, styrene-maleic mono-ester copolymer, methyl acrylate-methacrylic acid copolymer, methacrylate-methacrylic and acid-octyl acrylate copolymer.
2. The pharmaceutical composition of claim 1 comprising from 44% to 57% by weight of an amorphous cathepsin K inhibitor system and from 43% to 66% by weight of excipients comprising a diluent, a glidant, a lubricant, a surfactant and a disintegrant.
3. The pharmaceutical composition of claim 2 comprising 50.0% by weight of an amorphous cathepsin K inhibitor system and 50.0% by weight of excipients comprising a diluent, a glidant, a lubricant, a surfactant and a disintegrant.
4. The pharmaceutical composition of claim 1 wherein the polymer is selected from the group consisting of HPMCAS and copovidone.
5. The pharmaceutical composition of claim 4 wherein the polymer is selected from the group consisting of HPMCAS-HF, HPMCAS-MF, HPMCAS-LF and Kollidon VA64.
6. The pharmaceutical composition of claim 5 wherein the polymer is HPMCAS-HF.
7. The pharmaceutical composition of claim 6 wherein the diluent is spray-dried lactose, the glidant is silicone dioxide, the lubricant is magnesium stearate, the surfactant is sodium laurel sulfate, and the disintegrant is croscarmellose sodium.
8. A method of improving the absorption of a cathespin K inhibitor by combining the cathepsin K inhibitor with a polymer to form an amorphous system, wherein the cathepsin K inhibitor is N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide, and the polymer is selected from the group consisting of HPMCAS, copovidone, cellulose acetate phthalate, cellulose acetate succinate, methylcellulose phthalate, ethylhydroxycellulose phthalate, polyvinylacetatephthalate, polyvinylbutyrate acetate, vinyl acetate-maleic anhydride copolymer, styrene-maleic mono-ester copolymer, methyl acrylate-methacrylic acid copolymer, methacrylate-methacrylic and acid-octyl acrylate copolymer.
9. The method of claim 8 wherein the cathepsin K inhibitor is is N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide, and the polymer is HPMCAS-HF.