Solid oral dosage formulation of HCV inhibitor in the amorphous state
Described herein are solid oral dosage forms containing Compound (1) or a pharmaceutically acceptable salt thereof (Formula 1), wherein Compound (1) is in the amorphous state. Also described are solid oral dosage forms comprising a composition of Compound (1) in the amorphous state and one or more pharmaceutically acceptable excipients. Compound (1) is a specific inhibitor of the hepatitis C virus (HCV) NS3/4A serine protease. Thus, also described herein are methods for using the described solid oral dosage forms in the treatment of HCV infection. Also described are processes for the manufacture of the solid oral dosage forms.
1. A solid oral dosage composition comprising:
Compound (1), or a pharmaceutically acceptable salt thereof, in the amorphous state:
and
either a water-soluble base; or a hydrophilic, solid dispersion-forming polymer; or
both a water-soluble base and a hydrophilic, solid dispersion-forming polymer.
2. A solid oral dosage composition according to claim 1 , which comprises a water-soluble base.
3. A solid oral dosage composition according to claim 1 , which comprises a hydrophilic, solid dispersion-forming polymer.
4. A solid oral dosage composition according to claim 1 , which comprises a water-soluble base and a hydrophilic, solid dispersion-forming polymer.
5. A solid oral dosage composition according to claim 3 , wherein Compound (1), or a pharmaceutically acceptable salt thereof, in the amorphous state is in the form of an amorphous solid dispersion in the polymer.
6. A solid oral dosage composition according to claim 1 , further comprising a surfactant.
7. A solid oral dosage composition according to claim 1 , in the form of a tablet.
8. A solid oral dosage composition according to claim 1 , in the form of a powder.
9. A solid oral dosage composition according to claim 1 , which is storage stable at room temperature.
10. The solid oral dosage composition according to claim 1 , wherein the water-soluble base is arginine, tromethamine, meglumine, carbonate buffer or sodium carbonate.
11. The solid oral dosage composition according to claim 1 , wherein the water-soluble base is arginine.
12. The solid oral dosage composition according to claim 1 , wherein the water-soluble base is dispersed with the Compound (1), or a pharmaceutically acceptable salt thereof, in the amorphous state.
13. The solid oral dosage composition according to claim 1 , wherein the hydrophilic, solid dispersion-forming polymer is a polyvinylpyrrolidine or copolymer thereof or a cellulosic polymer.
14. The solid oral dosage composition according to claim 1 , wherein the hydrophilic, solid dispersion-forming polymer is a polyvinylpyrrolidine.
15. The solid oral dosage composition according to claim 6 , wherein the surfactant is an anionic surfactant.
16. The solid oral dosage composition according to claim 6 , wherein the surfactant is selected from alkyl sulfates, alkyl ether sulfates, sulfonates, phosphates and carboxylates.
17. The composition of claim 1 , wherein the amount of degradation product Compound X:
in the composition is below a level of about 400 μg when the composition contains a full daily dose of Compound (1) or pharmaceutically acceptable salt thereof in either single or multiple dosage units.
18. The solid oral dosage composition according to claim 6 , wherein the surfactant is sodium dodecyl sulfate (SDS).
19. A solid oral dosage composition according to claim 4 , wherein Compound (1), or a pharmaceutically acceptable salt thereof, in the amorphous state is in the form of an amorphous solid dispersion in the polymer.