Solid compositions
View Patent ↗The present invention features solid compositions comprising Compound I A , I B or I C , or a pharmaceutically acceptable salt thereof, in an amorphous form. In one embodiment, Compound I A , I B or I C , or a pharmaceutically acceptable salt thereof, is formulated in an amorphous solid dispersion which comprises a pharmaceutically acceptable hydrophilic polymer and preferably a pharmaceutically acceptable surfactant.
1. A solid composition comprising
(1) a compound, or a pharmaceutically acceptable salt thereof, in an amorphous form,
(2) a pharmaceutically acceptable hydrophilic polymer; and
(3) optionally a pharmaceutically acceptable surfactant,
wherein said compound is selected from the group consisting of:
methyl[(2S)-1-{(2S)-2-[4-(4-{5-(4-{2-[(2S)-1-{(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl}pyrrolidin-2-yl]-1H-imidazol-4-yl}phenyl)-1-[6-(piperidin-1-yl)pyridin-3-yl]-1H-pyrrol-2-yl}phenyl)-1H-imidazol-2-yl]pyrrolidin-1-yl}-3-methyl-1-oxobutan-2-yl]carbamate (Compound I A ),
methyl{(2S,3R)-1-[(2S)-2-{6-[(2R,5R)-1-(4-tert-butylphenyl)-5-(2-{(2S)-1-[N-(methoxycarbonyl)-O-methyl-L-threonyl]pyrrolidin-2-yl}-1H-benzimidazol-6-yl)pyrrolidin-2-yl]-1H-benzimidazol-2-yl}pyrrolidin-1-yl]-3-methoxy-1-oxobutan-2-yl}carbamate (Compound I B ), and
methyl{(2S)-1-[(2S)-2-{5-[(2R,5R)-1-[2,5-difluoro-4-(trifluoromethyl)phenyl]-5-{2-[(2S)-1-{(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl}pyrrolidin-2-yl]-1H-benzimidazol-5-yl}pyrrolidin-2-yl]-1H-benzimidazol-2-yl}pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl}carbamate (Compound I C ).
2. The composition of claim 1 , comprising a solid dispersion which includes:
(1) said compound or salt thereof, and
(2) said polymer.
3. The composition of claim 2 , wherein said polymer has a T g of at least 50° C.
4. The composition of claim 3 , further comprising said surfactant.
5. The composition of claim 4 , wherein said solid dispersion comprises said surfactant.
6. The composition of claim 4 , wherein said polymer is a homopolymer or copolymer of N-vinyl pyrrolidone.
7. The composition of claim 4 , wherein said polymer is copovidone.
8. The composition of claim 7 , wherein said surfactant is D-alpha-tocopheryl polyethylene glycol 1000 succinate.
9. The composition of claim 7 , wherein said surfactant is a combination of D-alpha-tocopheryl polyethylene glycol 1000 succinate and propylene glycol monolaurate.
10. The composition of claim 7 , wherein said surfactant is sorbitan mono laurate.
11. The composition of claim 4 , wherein said solid dispersion is an amorphous solid dispersion.
12. The composition of claim 4 , where said solid dispersion is a solid solution which comprises said surfactant.
13. The composition of claim 1 , further comprising another anti-hepatitis C virus (HCV) agent.
14. The composition of claim 1 , further comprising an HCV protease inhibitor.
15. The composition of claim 1 , further comprising an HCV polymerase inhibitor.
16. The composition of claim 4 , wherein said compound is Compound I A .
17. The composition of claim 4 , wherein said compound is Compound I B .
18. The composition of claim 4 , wherein said compound is Compound I C .
19. A process of making the composition of claim 1 , comprising dissolving said compound or salt in a solvent.
20. The process of claim 19 , wherein said solvent is said polymer.
21. A method of treating HCV comprising administering the composition of claim 1 to a patient in need thereof.
22. The method of claim 21 , comprising administering another anti-HCV agent to said patient.