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. A method of treating hepatitis C in a human patient in need thereof comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises:
a) from about 1% to about 25% w/w of a solid dispersion comprising Compound I dispersed within a polymer matrix formed by copovidone, wherein the weight ratio of Compound I to copovidone in the solid dispersion is about 1:1 and wherein Compound I is substantially amorphous having the formula:
b) from about 35% to about 45% w/w of substantially crystalline sofosbuvir having the formula:
c) from about 30% to about 40% w/w of microcrystalline cellulose;
d) from about 1% to about 5% w/w of croscarmellose sodium; and
e) from about 0.5% to about 2.5% w/w of magnesium stearate.
2. The method of claim 1 , wherein the crystalline sofosbuvir has XRPD 2θ-reflections at about: 6.1 and 12.7° 2θ±0.2.
3. The method of claim 1 , wherein the crystalline sofosbuvir has XRPD 2θ-reflections at about: 6.1, 20.1, and 20.8° 2θ±0.2.
4. The method of claim 1 , wherein the pharmaceutical composition comprises about 40% w/w of sofosbuvir.
5. The method of claim 1 , wherein the pharmaceutical composition comprises about 20% w/w of the solid dispersion.
6. The method of claim 1 , wherein the pharmaceutical composition comprises about 35.5% w/w of microcrystalline cellulose.
7. The method of claim 1 , wherein the pharmaceutical composition comprises about 3% w/w of croscarmellose sodium.
8. The method of claim 1 , wherein the pharmaceutical composition comprises about 1.5% w/w of magnesium stearate.
9. The method of claim 1 , wherein the pharmaceutical composition is administered for about 12 weeks.
10. A method of treating hepatitis C in a human patient in need thereof comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises:
a) about 20% w/w of a solid dispersion comprising Compound I dispersed within a polymer matrix formed by copovidone, wherein the weight ratio of Compound I to copovidone in the solid dispersion is about 1:1 and wherein Compound I is substantially amorphous having the formula:
b) about 40% w/w of substantially crystalline sofosbuvir having the formula:
c) about 35.5% w/w of microcrystalline cellulose;
d) about 3% w/w of croscarmellose sodium; and
e) about 1.5% w/w of magnesium stearate.
11. The method of claim 10 , wherein the crystalline sofosbuvir has XRPD 2θ-reflections at about: 6.1 and 12.7° 2θ±0.2.
12. The method of claim 10 , wherein the crystalline sofosbuvir has XRPD 2θ-reflections at about: 6.1, 20.1, and 20.8° 2θ±0.2.
13. The method of claim 10 , wherein the pharmaceutical composition is administered for about 12 weeks.
14. A method of treating hepatitis C in a human patient in need thereof comprising administering to the patient 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 I to 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.
15. The method of claim 14 wherein the pharmaceutical composition is in the form of a tablet comprising a film coating.
16. The method of claim 15 , wherein the film coating is a polyvinylalcohol-based coating.
17. The method of claim 14 , wherein the crystalline sofosbuvir has XRPD 2θ-reflections at about: 6.1 and 12.7° 2θ±0.2.
18. The method of claim 14 , wherein the crystalline sofosbuvir has XRPD 2θ-reflections at about: 6.1, 20.1, and 20.8° 2θ±0.2.
19. The method of claim 14 , wherein the pharmaceutical composition is administered for about 12 weeks.