COMBINATION FORMULATION OF TWO ANTIVIRAL COMPOUNDS
Disclosed are pharmaceutical compositions comprising Compound I, having the formula: and an effective amount of sofosbuvir wherein the sofosbuvir is substantially crystalline. Also disclosed are methods of use for the pharmaceutical composition.
1 .- 59 . (canceled)
60 . A method of treating hepatitis C in a human patient in need thereof comprising administering to the patient once daily a pharmaceutical composition, wherein the pharmaceutical composition comprises:
a) about 200 mg of a solid dispersion comprising Compound I dispersed within a polymer matrix formed by copovidone, wherein the weight ratio of Compound Ito copovidone in the solid dispersion is about 1:1 and wherein Compound I is substantially amorphous having the formula:
b) about 400 mg of substantially crystalline sofosbuvir having the formula:
c) about 355 mg of microcrystalline cellulose;
d) about 30 mg of croscarmellose sodium; and
e) about 15 mg of magnesium stearate.
61 . The method of claim 60 , wherein the pharmaceutical composition is in the form of a tablet comprising a film coating.
62 . The method of claim 61 , wherein the film coating is a polyvinylalcohol-based coating.
63 . The method of claim 60 , wherein the crystalline sofosbuvir has XRPD 2θ-reflections at about: 6.1 and 12.7° 2θ±0.2.
64 . The method of claim 60 , wherein the crystalline sofosbuvir has XRPD 2θ-reflections at about: 6.1, 20.1, and 20.8° 2θ±0.2.
65 . The method of claim 60 , wherein the pharmaceutical composition is administered for about 12 weeks.
66 . The method of claim 60 , wherein the patient is infected with hepatitis C virus of genotype 1.
67 . The method of claim 60 , wherein the patient is infected with hepatitis C virus of genotype 2.
68 . The method of claim 60 , wherein the patient is infected with hepatitis C virus of genotype 3.
69 . The method of claim 60 , wherein the patient is infected with hepatitis C virus of genotype 4.
70 . The method of claim 60 , wherein the patient is infected with hepatitis C virus of genotype 5.
71 . The method of claim 60 , wherein the patient is infected with hepatitis C virus of genotype 6.
72 . The method of claim 60 , wherein the patient is not suffering from cirrhosis.