Hydrogen sulfate salt
The present invention relates to Compound 1 hydrogen sulfate salt and solvates, crystalline forms and amorphous forms thereof, and to processes for their preparation.
1. A crystalline hydrogen sulfate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide, wherein said hydrogen sulfate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide has an X-ray powder diffraction pattern with specific peaks at about 2-theta equal to 24.59°, 20.97°, 27.65°, 12.24°, and 17.02°.
2. The crystalline hydrogen sulfate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide according to claim 1 , wherein said hydrogen sulfate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide has an X-ray powder diffraction pattern with specific peaks at about 2-theta equal to 24.59°, 20.97°, 23.99°, 27.65°, 12.24°, 23.49°, 24.30°, 17.02°, 25.91° and 22.50°.
3. The crystalline hydrogen sulfate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide according to claim 1 , which has a powder X-ray diffraction pattern substantially the same as the X-ray powder diffraction pattern shown in FIG. 1 .
4. The crystalline hydrogen sulfate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide according to claim 1 , wherein said hydrogen sulfate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide has an X-ray powder diffraction pattern with specific peaks at about 2-theta equal to 24.59°, 20.97°, 27.65°, 12.24°, 23.49°, 23.99°, 17.02° and 25.91°.
5. A pharmaceutical composition comprising a crystalline hydrogen sulfate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide, wherein said hydrogen sulfate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide has an X-ray powder diffraction pattern with specific peaks at about 2-theta equal to 24.59°, 20.97°, 27.65°, 12.24° and 17.02°, and a pharmaceutically acceptable excipient.
6. The pharmaceutical composition of claim 5 , in a form for oral administration.
7. The pharmaceutical composition of claim 6 , formulated as a tablet, lozenge, hard or soft capsule, emulsion, dispersible powder or granule, syrup, elixir, oily suspension or aqueous suspension.
8. The pharmaceutical composition of claim 7 , formulated as a tablet or hard or soft capsule.
9. A pharmaceutical composition comprising a crystalline hydrogen sulfate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide, wherein said hydrogen sulfate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide has an X-ray powder diffraction pattern with specific peaks at about 2-theta equal to 24.59°, 20.97°, 23.99°, 27.65°, 12.24°, 23.49°, 24.30°, 17.02°, 25.91° and 22.50°, and a pharmaceutically acceptable excipient.
10. The pharmaceutical composition of claim 9 , in a form for oral administration.
11. The pharmaceutical composition of claim 10 , formulated as a tablet, lozenge, hard or soft capsule, emulsion, dispersible powder or granule, syrup, elixir, oily suspension or aqueous suspension.
12. The pharmaceutical composition of claim 11 , formulated as a tablet or hard or soft capsule.
13. A pharmaceutical composition, comprising a crystalline hydrogen sulfate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide which has a powder X-ray diffraction pattern substantially the same as the X-ray powder diffraction pattern shown in FIG. 1 , and a pharmaceutically acceptable excipient.
14. The pharmaceutical composition of claim 13 , in a form for oral administration.
15. The pharmaceutical composition of claim 14 , formulated as a tablet, lozenge, hard or soft capsule, emulsion, dispersible powder or granule, syrup, elixir, oily suspension or aqueous suspension.
16. The pharmaceutical composition of claim 15 , formulated as a tablet or hard or soft capsule.
17. A pharmaceutical composition comprising a crystalline hydrogen sulfate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide, wherein said hydrogen sulfate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide has an X-ray powder diffraction pattern with specific peaks at about 2-theta equal to 24.59°, 20.97°, 27.65°, 12.24°, 23.49°, 23.99°, 17.02° and 25.91°, and a pharmaceutically acceptable excipient.
18. The pharmaceutical composition of claim 17 , in a form for oral administration.
19. The pharmaceutical composition of claim 18 , formulated as a tablet, lozenge, hard or soft capsule, emulsion, dispersible powder or granule, syrup, elixir, oily suspension or aqueous suspension.
20. The pharmaceutical composition of claim 19 , formulated as a tablet or hard or soft capsule.