Compositions containing an ERK inhibitor

Claims

1. A pharmaceutical composition containing compound I having the formula: or a pharmaceutically acceptable salt or solvate thereof, and a water-soluble polymer.

2. The composition according to claim 1, characterized in that the water-soluble polymer is polyvinylpyrrolidone / vinyl acetate (PVPVA), hydroxypropyl methylcellulose (HPMC) or hydroxypropyl methylcellulose acetate succinate (HPMCAS).

3. The composition according to claim 1, characterized in that the water-soluble polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS).

4. The composition according to claim 1, containing a hydrate of the free base of compound I.

5. The composition according to claim 1, containing the monohydrate of the free base of compound I.

6. A solid dispersion containing compound I having the formula: or a pharmaceutically acceptable salt or solvate thereof, wherein compound I or a pharmaceutically acceptable salt or solvate thereof is molecularly dispersed in a polymer matrix containing hydroxypropyl methylcellulose acetate succinate (HPMCAS).

7. A solid dispersion according to claim 6, characterized in that compound I or a pharmaceutically acceptable salt or solvate thereof is present in the solid dispersion in an amount of from about 20% to about 50% by weight of the solid dispersion.

8. A solid dispersion according to claim 6, characterized in that compound I or a pharmaceutically acceptable salt or solvate thereof is present in the solid dispersion in an amount of from about 20% to about 40% by weight of the solid dispersion.

9. A solid dispersion according to claim 6, characterized in that compound I or a pharmaceutically acceptable salt or solvate thereof is present in the solid dispersion in an amount of from about 20% to about 30% by weight of the solid dispersion.

10. A solid dispersion according to claim 6, characterized in that compound I or its pharmaceutically acceptable salt or solvate is essentially amorphous.

11. A solid dispersion according to claim 6, characterized in that at least 98% of compound I or its pharmaceutically acceptable salt or solvate is in amorphous form.

12. A solid dispersion according to claim 6, characterized in that compound I is a free base or its solvate.

13. A solid dispersion according to claim 6, characterized in that compound I is a hydrate of the free base.

14. The solid dispersion of claim 6, wherein the ratio of the amount by weight of compound I or a pharmaceutically acceptable salt or solvate thereof in the solid dispersion to the amount by weight of HPMCAS in the solid dispersion is from about 1:1 to about 1:

5.

15. The solid dispersion of claim 6, wherein the ratio of the amount by weight of compound I or a pharmaceutically acceptable salt or solvate thereof in the solid dispersion to the amount by weight of HPMCAS in the solid dispersion is from about 1:2 to about 1:

4.

16. A solid dispersion according to claim 6, characterized in that the ratio of the amount by weight of compound I in the solid dispersion to the amount by weight of HPMCAS in the solid dispersion is approximately 1:

3.

17. A solid dispersion according to any one of claims 6 to 16, characterized in that the HPMCAS is present in an amount of more than about 50% by weight of the solid dispersion.

18. The solid dispersion of any one of claims 6 to 16, wherein the HPMCAS is present in an amount of from about 60% to about 80% by weight of the solid dispersion.

19. A pharmaceutical composition containing a solid dispersion according to any one of claims 6-18.

20. The pharmaceutical composition according to claim 19, formulated in the form of a tablet.

21. A pharmaceutical composition according to any one of claims 19-20, formulated in the form of a tablet containing an intragranular layer and an extragranular layer.

22. A pharmaceutical composition according to any one of paragraphs 19-21, characterized in that the solid dispersion constitutes approximately 40-70% by weight of the tablet.

23. A pharmaceutical composition according to any one of paragraphs 19-22, characterized in that the solid dispersion constitutes approximately 60% by weight of the tablet.

24. A pharmaceutical composition according to any one of paragraphs 19-23, characterized in that the intragranular layer of the tablet additionally contains: approximately 8-18% by weight microcrystalline cellulose; approximately 8-18% by weight of lactose monohydrate; approximately 2-8% by weight croscarmellose sodium; approximately 0.5-2% by weight of non-pyrogenic silicon dioxide; and approximately 0.1-0.5% by weight magnesium stearate.

25. A pharmaceutical composition according to any one of paragraphs 19-24, characterized in that the extragranular layer of the tablet contains: approximately 0-14% by weight microcrystalline cellulose; approximately 0.14% by weight of lactose monohydrate; approximately 2.8% by weight croscarmellose sodium; approximately 0.5-2% by weight of non-pyrogenic silicon dioxide; and approximately 0.1-0.5% by weight magnesium stearate.

26. A pharmaceutical composition according to any one of paragraphs 19-25, characterized in that said tablet is film-coated.

27. A tablet containing a solid dispersion, wherein the solid dispersion contains compound I having the formula: or a pharmaceutically acceptable salt or solvate thereof, wherein compound I or a pharmaceutically acceptable salt or solvate thereof is molecularly dispersed in a polymer matrix containing hydroxypropyl methylcellulose acetate succinate (HPMCAS); and the ratio of the amount by weight of compound I or a pharmaceutically acceptable salt or solvate thereof in the solid dispersion to the amount by weight of HPMCAS in the solid dispersion is from about 1:1 to about 1:

5.

28. The tablet of claim 27, wherein the ratio of the amount by weight of compound I or a pharmaceutically acceptable salt or solvate thereof in the solid dispersion to the amount by weight of HPMCAS in the solid dispersion is from about 1:2 to about 1:

4.

29. The tablet according to claim 27, characterized in that the ratio of the amount by weight of compound I in the solid dispersion to the amount by weight of HPMCAS in the solid dispersion is approximately 1:

3.

30. The tablet according to claim 27, characterized in that compound I or its pharmaceutically acceptable salt or solvate is essentially amorphous.

31. A tablet according to claim 27, characterized in that at least 98% of compound I or its pharmaceutically acceptable salt or solvate is in amorphous form.

32. The tablet according to claim 27, characterized in that compound I is a free base or its solvate.

33. The tablet according to claim 27, characterized in that compound I is a hydrate of the free base.

34. The tablet according to claim 27, characterized in that compound I is a monohydrate of the free base.

35. A tablet composition of compound I having the formula: or a pharmaceutically acceptable salt or solvate thereof, containing: intragranular part containing: about 60% by weight of a solid dispersion of compound I or a pharmaceutically acceptable salt or solvate thereof and HPMCAS, wherein compound I or a pharmaceutically acceptable salt or solvate thereof is substantially amorphous and molecularly dispersed in a polymer matrix comprising hydroxypropyl methylcellulose acetate succinate (HPMCAS), and the ratio of the amount by weight of compound I or a pharmaceutically acceptable salt or solvate thereof in the solid dispersion to the amount by weight of HPMCAS in the solid dispersion is about 1:3; approximately 14% by weight microcrystalline cellulose; approximately 13.5% by weight of lactose monohydrate; approximately 6% by weight croscarmellose sodium; approximately 1% by weight of non-pyrogenic silicon dioxide; and approximately 0.25% by weight magnesium stearate; extragranular part containing: approximately 4% by weight croscarmellose sodium; approximately 1% by weight of non-pyrogenic silicon dioxide; and approximately 0.25% by weight magnesium stearate.

36. The tablet composition of claim 35, wherein the HPMCAS has an acetyl group content of about 7 to about 11 percent by weight and a succinoyl group content of about 10 to about 14 percent by weight of the HPMCAS.

37. Use of a composition according to any one of claims 1-36 for the treatment of cancer.

38. A method of treating cancer, comprising administering a composition according to any one of claims 1 to 36 to an individual in need thereof.

39. A method for producing a solid dispersion according to claim 6, comprising spray drying a solution of compound I or a pharmaceutically acceptable salt or solvate thereof and HPMCAS in a solvent, wherein the solids content of said solution is up to about 25% by weight.

40. The method according to paragraph 39, characterized in that said solvent is acetone or methanol.

41. The method according to claim 39, characterized in that the solid dispersion is obtained by spray drying a solution of compound I or a pharmaceutically acceptable salt or solvate thereof and HPMCAS in acetone, wherein the solids content of the solution in acetone is up to about 10% by weight.

42. The method according to claim 39, characterized in that compound I is a hydrate of the free base.

43. The method according to claim 39, characterized in that compound I is a monohydrate of the free base.