SOLID COMPOSITIONS
The present invention features solid compositions comprising amorphous Compound I. A solid dispersion of the present invention also contains a pharmaceutically acceptable hydrophilic polymer and a pharmaceutically acceptable surfactant. 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) (2R,6S,13aS,14aR,16aS,Z)-N-(cyclopropylsulfonyl)-6-(5-methylpyrazine-2-carboxamido)-5,16-dioxo-2-(phenanthridin-6-yloxy)-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxamide, 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 (2R,6S,13aS,14aR,16aS,Z)-N-(cyclopropylsulfonyl)-6-(5-methylpyrazine-2-carboxamido)-5,16-dioxo-2-(phenanthridin-6-yloxy)-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxamide, or said pharmaceutically acceptable 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 , 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 propylene glycol laurate.
10 . The composition of claim 9 , further comprising D-alpha-tocopheryl polyethylene glycol 1000 succinate.
11 . The composition of claim 8 , wherein said surfactant is polysorbate.
12 . The composition of claim 8 , wherein said surfactant is polysorbate 80.
13 . The composition of claim 8 , wherein said solid dispersion is an amorphous solid dispersion.
14 . The composition of claim 8 , where said solid dispersion is a solid solution which comprises said surfactant.
15 . The composition of claim 1 , further comprising ritonavir.
16 . The composition of claim 2 , wherein said solid dispersion further comprises ritonavir.
17 . The composition of claim 6 , wherein said solid dispersion further comprises ritonavir.
18 . The composition of claim 14 , wherein said solid solution further comprises ritonavir.
19 . A process of making the composition of claim 1 , comprising drying a solvent in a liquid solution, wherein said solution comprises:
(1) (2R,6S,13aS,14aR,16aS,Z)—N-(cyclopropylsulfonyl)-6-(5-methylpyrazine-2-carboxamido)-5,16-dioxo-2-(phenanthridin-6-yloxy)-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxamide, or a pharmaceutically acceptable salt thereof;
(2) said polymer; and
(3) said surfactant.
20 . A process of making the composition of claim 1 , comprising solidifying a melt, wherein said melt comprises:
(1) (2R,6S,13aS,14aR,16aS,Z)—N-(cyclopropylsulfonyl)-6-(5-methylpyrazine-2-carboxamido)-5,16-dioxo-2-(phenanthridin-6-yloxy)-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxamide, or a pharmaceutically acceptable salt thereof;
(2) said polymer; and
(3) said surfactant.