Combination formulation of two antiviral compounds

• US 9,757,406 B2
• Filed: 09/30/2016
• Issued: 09/12/2017
• Est. Priority Date: 08/27/2013
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Pharmasset LLC (Gilead Sciences Inc.)
• Inventors: Gorman, Eric, Mogalian, Erik, Oliyai, Reza, Stefanidis, Dimitrios, Wiser, Lauren, Zia, Vahid
• Primary Examiner(s): Song, Jianfeng
• Application Number:
  US15/282,128
• Publication Number:
  US 20170095499A1
• Time in Patent Office: 347 Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/4188 condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
• CPC Class Codes: A61K 31/7056 containing five-membered rings with nitrogen as a ring hetero atom
• CPC Class Codes: A61K 31/7072 having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
• CPC Class Codes: A61K 9/1623 Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/284 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

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.

Claims

1. A pharmaceutical composition comprising:

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;

2. The pharmaceutical composition of claim 1, wherein the crystalline sofosbuvir has XRPD 2θ

-reflections at about;

6.1 and 12.7 °

2θ

±

0.2.

3. The pharmaceutical composition 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 pharmaceutical composition of claim 1, comprising about 40% w/w of sofosbuvir.

5. The pharmaceutical composition of claim 1, comprising about 20% w/w of the solid dispersion.

6. The pharmaceutical composition of claim 1, comprising about 35.5% w/w of microcrystalline cellulose.

7. The pharmaceutical composition of claim 1, comprising about 3% w/w of croscarmellose sodium.

8. The pharmaceutical composition of claim 1, comprising about 1.5% w/w of magnesium stearate.

9. A pharmaceutical composition comprising:

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;

10. The pharmaceutical composition of claim 9, wherein the crystalline sofosbuvir has XRPD 2θ

-reflections at about;

6.1 and 12.7 °

2θ

±

0.2.

11. The pharmaceutical composition of claim 9, wherein the crystalline sofosbuvir has XRPD 2θ

-reflections at about;

6.1, 20.1, and 20.8 °

2θ

±

0.2.

12. A pharmaceutical composition comprising:

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;

13. The pharmaceutical composition of claim 12 which is in the form of a tablet comprising a film coating.

14. The tablet of claim 13, wherein the film coating is a polyvinylalcohol-based coating.

15. The pharmaceutical composition of claim 12, wherein the crystalline sofosbuvir has XRPD 2θ

-reflections at about;

6.1 and 12.7 °

2θ

±

0.2.

16. The pharmaceutical composition of claim 12, wherein the crystalline sofosbuvir has XRPD 2θ

-reflections at about;

6.1, 20.1, and 20.8 °

2θ

±

0.2.