Use of solid carrier particles to improve the processability of a pharmaceutical agent

Patent metadata

Field	Value
Publication number	US-10039718-B2
Application number	US-43451309-A
Country	US
Kind code	B2
Filing date	May 1, 2009
Priority date	May 2, 2008
Publication date	Aug 7, 2018
Grant date	Aug 7, 2018

Abstract

The invention provides a composition comprising, a compound of formula (I):

or a pharmaceutically acceptable salt thereof and a plurality of solid carrier particles, as well as methods for using the composition to inhibit the activity of cytochrome P-450.

First claim

What is claimed is:

1. A composition comprising a plurality of hydrophilic fumed silicon dioxide particles and a compound of formula (I):

wherein the compound of formula (I) is in the pores or on the surface of the silicon dioxide particles.

2. The composition of claim 1 wherein the silicon dioxide particles have a mean grain diameter of 20-40 micron.

3. The composition of claim 1 wherein the silicon dioxide particles have a BET surface area of at least 150 m 2 /g.

4. The composition of claim 1 wherein the compound of formula (I) has an enriched concentration of 99±1% of the stereoisomer of formula (Ia):

5. A method of preparing the composition of claim 1 comprising combining the compound of formula (I):

a suitable solvent, and a plurality of hydrophilic fumed silicon dioxide particles to provide a mixture, wherein the compound of formula (I) is in the pores or on the surface of the silicon dioxide particles.

6. The method of claim 5 wherein the silicon dioxide particles have a mean grain diameter of 20-40 micron.

7. The method of claim 5 wherein the silicon dioxide particles have a BET surface area of at least 150 m 2 /g.

8. The method of claim 5 wherein the solvent is a (C 1 -C 6 ) alcohol.

9. The method of claim 5 wherein the solvent comprises ethanol.

10. A pharmaceutical composition comprising a plurality of hydrophilic fumed silicon dioxide particles; a compound of formula (I):

tenofovir disoproxil fumarate; emtricitabine; and elvitegravir; wherein the compound of formula (I) is in the pores or on the surface of the silicon dioxide particles.

11. The pharmaceutical composition of claim 10 wherein the silicon dioxide particles have a mean grain diameter of 20-40 micron.

12. The pharmaceutical composition of claim 10 wherein the silicon dioxide particles have a BET surface area of at least 150 m 2 /g.

13. The pharmaceutical composition of claim 10 wherein the compound of formula (I) has an enriched concentration of 99±1% of the stereoisomer of formula (Ia):

14. The composition of claim 4 , further comprising at least one additional therapeutic agent selected from the group consisting of HIV protease inhibiting compounds, HIV non-nucleoside inhibitors of reverse transcriptase, HIV nucleoside inhibitors of reverse transcriptase, HIV nucleotide inhibitors of reverse transcriptase, HIV integrase inhibitors, non-nucleoside inhibitors of HCV, CCR5 inhibitors, and combinations thereof, and a pharmaceutically acceptable excipient.

15. The composition of claim 14 , wherein the additional therapeutic agent is darunavir.

16. The composition of claim 14 , wherein the additional therapeutic agent is atazanavir.

17. The composition of claim 4 , comprising 150 mg±10% of the compound of formula (Ia).

18. The composition of claim 1 , wherein the silicon dioxide particles have a mean particle diameter of about 10 to about 120 micron and a BET surface area of about 40 to about 400 m 2 /g.

19. The composition of claim 1 , wherein the weight of the compound of formula (I) divided by the weight of the silicon dioxide particles in the composition is 1.0±0.5.

20. The composition of claim 1 , wherein the hygroscopicity of the silicon dioxide particles and the compound of formula (I) taken separately is higher than the hygroscopicity of the compound of formula (I) and silicon dioxide particles taken together.

21. The method of claim 5 , wherein the silicon dioxide particles have a mean particle diameter of about 10 to about 120 micron and a BET surface area of about 40 to about 400 m 2 /g.

22. The method of claim 5 , wherein the weight of the compound of formula (I) divided by the weight of the silicon dioxide particles in the mixture is 1.0±0.5.

23. The method of claim 5 , wherein the hygroscopicity of the silicon dioxide particles and the compound of formula (I) taken separately is higher than the hygroscopicity of the compound of formula (I) and silicon dioxide particles taken together.

24. The pharmaceutical composition of claim 10 , wherein the silicon dioxide particles have a mean particle diameter of about 10 to about 120 micron and a BET surface area of about 40 to about 400 m 2 /g.

25. The pharmaceutical composition of claim 10 , wherein the weight of the compound of formula (I) divided by the weight of the silicon dioxide particles in the composition is 1.0±0.5.

26. The pharmaceutical composition of claim 10 , wherein the hygroscopicity of the silicon dioxide particles and the compound of formula (I) taken separately is higher than the hygroscopicity of the compound of formula (I) and silicon dioxide particles taken together.

Assignees

• Koziara Joanna M
• Menning Mark M
• Strickley Robert G
• Yu Richard
• Kearney Brian P
• Mathias Anita A
• Gilead Sciences Inc

Inventors

• Koziara Joanna M
• Menning Mark M
• Strickley Robert G
• Yu Richard
• Kearney Brian P
• Mathias Anita A

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P31/18

  for HIV · CPC title

• A61P31/12

  Antivirals · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61K9/2009 Primary

  Inorganic compounds · CPC title