Granted Patent B1

US 12,357,577 · App. 18/431,038 · Granted Jul 15, 2025

Inventors: Kimberly T. Barrett (Pacifica, CA); Elaine Bunyan (San Francisco, CA)

Assignee: Gilead Sciences, Inc.

A61K9/2054A61K9/2009A61K9/2027A61K9/2866A61K31/706

Abstract

Claims (67)

1. A pharmaceutical formulation, comprising:

(i) about 175 mg or about 350 mg of a compound expressed by formula I, or a pharmaceutically acceptable salt thereof;

(ii) a filler;

(iii) a disintegrating agent; and

(iv) a lubricant;

wherein the compound of Formula I is present in an amount of about 45 wt % to about 55 wt %.

2. The pharmaceutical formulation of claim 1 , wherein the pharmaceutical formulation comprises:

(i) the compound of Formula I in an amount of about 50 wt %;

(ii) the filler in an amount of about 44 wt % to about 46 wt %;

(iii) the disintegrating agent in an amount of about 3 wt % to about 5 wt %; and

(iv) the lubricant in an amount of about 0.5 wt % to about 2 wt %.

3. The pharmaceutical formulation according to claim 1 , wherein the filler is microcrystalline cellulose, lactose, mannitol, or dicalcium phosphate; the disintegrating agent is starch, pre-gelatinized starch, hydroxypropyl starch, celluloses, cross-linked PVP (crospovidone), sodium starch glycolate, or croscarmellose sodium; and the lubricant is stearic acid, sodium stearyl fumarate, or magnesium stearate.

4. The pharmaceutical formulation of claim 1 , wherein the filler is microcrystalline cellulose, the disintegrating agent is crospovidone and the lubricant is magnesium stearate.

5. The pharmaceutical formulation of claim 1 , wherein the pharmaceutical formulation comprises about 175 mg of the compound of Formula I.

6. The pharmaceutical formulation of claim 1 , wherein the pharmaceutical formulation comprises about 350 mg of the compound of Formula I.

7. The pharmaceutical composition of claim 1 , wherein the compound is the freebase of Formula I.

8. The pharmaceutical composition of claim 1 , wherein the compound is a crystalline form of the freebase of Formula I which is characterized by an X-ray powder diffraction pattern comprising degree 2θ-reflections (+/−0.2 degrees 2θ) at 9.8°, 16.0°, and 25.4°.

9. A tablet comprising the pharmaceutical formulation of claim 1 .

10. The tablet of claim 9 , wherein the tablet comprises:

(i) the compound of Formula I in an amount of about 50 wt %;

(ii) the filler in an amount of about 44 wt % to about 46 wt %;

(iii) the disintegrating agent in an amount of about 3 wt % to about 5 wt %; and

(iv) the lubricant in an amount of about 0.5 wt % to about 2 wt %.

11. The tablet of claim 9 , wherein the filler is microcrystalline cellulose, lactose, mannitol, or dicalcium phosphate; the disintegrating agent is starch, pre-gelatinized starch, hydroxypropyl starch, celluloses, cross-linked PVP (crospovidone), sodium starch glycolate, or croscarmellose sodium; and the lubricant is stearic acid, sodium stearyl fumarate, magnesium stearate, or a combination thereof.

12. The tablet of claim 9 , wherein the filler is microcrystalline cellulose, the disintegrating agent is crospovidone and the lubricant is magnesium stearate.

13. The tablet of claim 9 , wherein the compound is the freebase of Formula I.

14. The tablet of claim 9 , wherein the compound is a crystalline form of the freebase of Formula I which is characterized by an X-ray powder diffraction pattern comprising degree 2θ-reflections (+/−0.2 degrees 2θ) at 9.8°, 16.0°, and 25.4°.

15. The tablet of claim 9 , comprising:

(i) the compound of Formula I in an amount of about 175 mg;

(ii) microcrystalline cellulose in an amount of about 157.5 mg;

(iii) crospovidone in an amount of about 14 mg; and

(iv) magnesium stearate in an amount of about 3.5 mg.

16. The tablet of claim 9 , comprising:

(i) the compound of Formula I in an amount of about 350 mg;

(ii) microcrystalline cellulose in an amount of about 315 mg;

(iii) crospovidone in an amount of about 28 mg; and

(iv) magnesium stearate in an amount of about 7 mg.

17. A tablet comprising (a) a tablet core and (b) a film coat; wherein the tablet core comprises:

(i) about 175 mg or about 350 mg of a compound of Formula I, or a pharmaceutically acceptable salt thereof;

(ii) a filler;

(iii) a disintegrating agent; and

(iv) a lubricant;

wherein the compound of Formula I is present in an amount of about 45 wt % to about 55 wt %.

18. The tablet of claim 17 , wherein the tablet core comprises:

(i) the compound of Formula I in an amount of about 50 wt %;

(ii) the filler in an amount of about 44 wt % to about 46 wt %;

(iii) the disintegrating agent in an amount of about 3 wt % to about 5 wt %; and

(iv) the lubricant in an amount of about 0.5 wt % to about 2 wt %.

19. The tablet of claim 17 , wherein the film coat comprises part-hydrolysed PVA, titanium dioxide, macrogol 3350, and talc.

20. The tablet of claim 17 , wherein the film coat comprises polyethylene glycol/macrogol polyvinyl alcohol graft copolymer, talc, titanium dioxide, glyceryl mono and dicaprylocaprate, and polyvinyl alcohol.

21. The tablet of claim 17 , wherein the film coat is white or yellow.

22. The tablet of claim 17 , wherein the filler is microcrystalline cellulose, lactose, mannitol, or dicalcium phosphate; the disintegrating agent is starch, pre-gelatinized starch, hydroxypropyl starch, celluloses, cross-linked PVP (crospovidone), sodium starch glycolate, or croscarmellose sodium; and the lubricant is stearic acid, sodium stearyl fumarate, or magnesium stearate.

23. The tablet of claim 17 , wherein the filler is microcrystalline cellulose, the disintegrating agent is crospovidone and the lubricant is magnesium stearate.

24. The tablet of claim 17 , wherein the tablet comprises about 175 mg of the compound of Formula I.

25. The tablet of claim 17 , wherein the tablet comprises about 350 mg of the compound of Formula I.

26. A tablet comprising (a) a tablet core and (b) a film coat; wherein the tablet core comprises:

(i) a compound of Formula I in an amount of about 175 mg;

(ii) microcrystalline cellulose in an amount of about 157.5 mg;

(iii) crospovidone in an amount of about 14 mg; and

(iv) magnesium stearate in an amount of about 3.5 mg; and

wherein the film coat comprises polyethylene glycol/macrogol polyvinyl alcohol graft copolymer, talc, titanium dioxide, glyceryl mono and dicaprylocaprate, and polyvinyl alcohol and wherein the film coat is white.

27. A tablet comprising (a) a tablet core and (b) a film coat; wherein the tablet core comprises:

(i) a compound of Formula I in an amount of about 350 mg;

(ii) microcrystalline cellulose in an amount of about 315 mg;

(iii) crospovidone in an amount of about 28 mg; and

(iv) magnesium stearate in an amount of about 7 mg; and

wherein the film coat comprises polyethylene glycol/macrogol polyvinyl alcohol graft copolymer, talc, titanium dioxide, glyceryl mono and dicaprylocaprate, and polyvinyl alcohol and wherein the film coat is yellow.

Assignments (1)

References Cited (400)