Solid compositions
View Patent ↗The present invention features solid compositions comprising amorphous Compound I. For instance, Compound I may be 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) dimethyl (2S,2′S)-1,1′-((2S,2′S)-2,2′-(4,4′-((2S,5S)-1-(4-tert-butylphenyl)pyrrolidine-2,5-diyl)bis(4,1-phenylene))bis(azanediyl)bis(oxomethylene)bis(pyrrolidine-2,1-diyl))bis(3-methyl-1-oxobutane-2,1-diyl)dicarbamate
or a pharmaceutically acceptable salt thereof, in an amorphous form;
(2) a pharmaceutically acceptable hydrophilic polymer; and
(3) a pharmaceutically acceptable surfactant.
2. The composition of claim 1 , comprising a solid dispersion which includes:
(1) said dimethyl (2S,2′S)-1,1′-((2S,2′S)-2,2′-(4,4′-((2S,5S)-1-(4-tert-butylphenyl)pyrrolidine-2,5-diyl)bis(4,1-phenylene))bis(azanediyl)bis(oxomethylene)bis(pyrrolidine-2,1-diyl))bis(3-methyl-1-oxobutane-2,1-diyl)dicarbamate, or said pharmaceutically acceptable salt thereof,
(2) said polymer, and
(3) said surfactant.
3. The composition of claim 2 , wherein said polymer has a T g of at least 50° C.
4. The composition of claim 3 , wherein said surfactant has a HLB value of at least 10.
5. The composition of claim 4 , further comprising another surfactant having a HLB value of below 10.
6. The composition of claim 3 , wherein said solid dispersion is an amorphous solid dispersion which further comprises said surfactant.
7. The composition of claim 3 , wherein said polymer is a homopolymer or copolymer of N-vinyl pyrrolidone.
8. The composition of claim 2 , wherein said polymer is copovidone.
9. The composition of claim 8 , wherein said surfactant is D-alpha-tocopheryl polyethylene glycol 1000 succinate.
10. The composition of claim 8 , wherein said surfactant is sorbitan mono laurate.
11. The composition of claim 8 , wherein said solid dispersion is an amorphous solid dispersion.
12. The composition of claim 8 , where said solid dispersion is a solid solution which comprises said surfactant.
13. The composition of claim 1 , further comprising another anti-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 1 , further comprising telaprevir or boceprevir.
17. The composition of claim 1 , further comprising an anti-HCV agent selected from the group consisting of ITMN-191, BI-201335, VBY-376, VX-500, PHX-B, ACH-1625, IDX136, IDX316, VX-813, SCH 900518, TMC-435, ITMN-191, MK-7009, IDX-PI, BI-201335, R7128, MK-3281, PF-868554, PF-4878691, IDX-184, IDX-375, PPI-461, BILB-1941, GS-9190, BMS-790052, ABT-333, and ABT-072.
18. The composition of claim 1 , wherein said composition comprises at least two pharmaceutically acceptable surfactants, one having an HLB value of at least 10 and the other having an HLB value of below 10.
19. The composition of claim 6 , wherein said composition comprises at least two pharmaceutically acceptable surfactants, one having an HLB value of at least 10 and the other having an HLB value of below 10.
20. The composition of claim 11 , wherein said composition comprises at least two pharmaceutically acceptable surfactants, one having an HLB value of at least 10 and the other having an HLB value of below 10.
21. The composition of claim 12 , wherein said composition comprises at least two pharmaceutically acceptable surfactants, one having an HLB value of at least 10 and the other having an HLB value of below 10.