Claims for Patent: 12,220,403

Summary for Patent: 12,220,403

Title:	Pharmaceutical composition
Abstract:	The invention concerns pharmaceutical compositions containing a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide and solvates, crystalline forms and amorphous forms thereof, to the use of said compositions as a medicament; and to processes for the preparation of said compositions.
Inventor(s):	Nicola Frances Bateman, Paul Richard Gellert, Kathryn Jane Hill
Assignee:	AstraZeneca AB , Array Biopharma Inc
Application Number:	US18/484,334
Patent Claims:	1. A pharmaceutical composition consisting of: (i) a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide; and (ii) d-alpha-tocopheryl polyethylene glycol 1000 succinate (Vitamin E TPGS); wherein the hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide is dispersed within the Vitamin E TPGS, the composition is semi-solid or solid at ambient temperature; and wherein the pharmaceutical composition contains less than about 1% (w/w) of a free base form of the 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide. 2. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition contains approximately 60% (w/w) to approximately 95% (w/w) of the Vitamin E TPGS. 3. The pharmaceutical composition of claim 2, wherein the composition contains approximately 75% (w/w) to approximately 85% (w/w) of Vitamin E TPGS. 4. The pharmaceutical composition of claim 2, wherein the composition contains approximately 85% (w/w) to approximately 90% (w/w) of Vitamin E TPGS. 5. The pharmaceutical composition of claim 2, wherein the composition contains approximately 65% (w/w) to approximately 80% (w/w) of Vitamin E TPGS. 6. The pharmaceutical composition of claim 2, wherein the composition contains approximately 90% (w/w) to approximately 95% (w/w) of Vitamin E TPGS. 7. The pharmaceutical composition of claim 1, wherein the dispersed hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide has a particle size of about 1 micron to about 20 microns. 8. The pharmaceutical composition of claim 1, wherein the hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide has a particle size distribution such that about 90% of the particles have a diameter of less than about 15 microns. 9. An oral capsule filled with the pharmaceutical composition of claim 1. 10. The oral capsule of claim 9, wherein greater than about 95% of the pharmaceutical composition is dissolved after about 50 minutes using the United States Pharmacopoeia Apparatus II procedure. 11. A pharmaceutical composition consisting of: (i) a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide; and (ii) a carrier matrix; wherein greater than about 90% by weight of the total amount of hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide is dispersed within the carrier matrix, the composition is semi-solid or solid at ambient temperature; wherein the carrier matrix consists of d-alpha-tocopheryl polyethylene glycol 1000 succinate (Vitamin E TPGS). 12. The pharmaceutical composition of claim 11, wherein the pharmaceutical composition contains approximately 60% (w/w) to approximately 95% (w/w) of the Vitamin E TPGS. 13. The pharmaceutical composition of claim 12, wherein the composition contains approximately 75% (w/w) to approximately 85% (w/w) of Vitamin E TPGS. 14. The pharmaceutical composition of claim 12, wherein the composition contains approximately 85% (w/w) to approximately 90% (w/w) of Vitamin E TPGS. 15. The pharmaceutical composition of claim 12, wherein the composition contains approximately 65% (w/w) to approximately 80% (w/w) of Vitamin E TPGS. 16. The pharmaceutical composition of claim 12, wherein the composition contains approximately 90% (w/w) to approximately 95% (w/w) of Vitamin E TPGS. 17. The pharmaceutical composition of claim 11, wherein the dispersed hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide has a particle size from about 1 micron to about 20 microns. 18. The pharmaceutical composition of claim 11, wherein the dispersed hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide has a particle size distribution such that about 90% of the particles have a diameter of less than about 15 microns. 19. The pharmaceutical composition of claim 11, wherein greater than about 95% by weight of the total amount of hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide is dispersed within the carrier matrix. 20. An oral capsule filled with the pharmaceutical composition of claim 11. 21. The oral capsule of claim 20, wherein greater than about 95% of the pharmaceutical composition is dissolved after about 50 minutes using the United States Pharmacopoeia Apparatus II procedure. 22. A process for stabilizing a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide against dissociation into its free base form, the process comprising: dispersing a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide into a carrier matrix consisting of Vitamin E TPGS, in order to obtain a homogenous mixture of finely divided particles that are dispersed throughout the carrier matrix, wherein the homogenous mixture contains less than about 1% (w/w) of the free base form of the 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide. 23. The process of claim 22, further comprising filling the homogenous mixture into a capsule. 24. The process of claim 22, wherein the homogenous mixture contains approximately 60% (w/w) to approximately 95% (w/w) of the Vitamin E TPGS. 25. The process of claim 22, wherein the homogenous mixture contains approximately 75% (w/w) to approximately 85% (w/w) of Vitamin E TPGS. 26. The process of claim 22, wherein the homogenous mixture contains approximately 85% (w/w) to approximately 90% (w/w) of Vitamin E TPGS. 27. The process of claim 22, wherein the homogenous mixture contains approximately 65% (w/w) to approximately 80% (w/w) of Vitamin E TPGS. 28. The process of claim 22, wherein the homogenous mixture contains approximately 90% (w/w) to approximately 95% (w/w) of Vitamin E TPGS. 29. The process of claim 22, wherein the homogenous mixture of finely divided particles has a particle size from about 1 micron to about 20 microns. 30. The process of claim 22, wherein the homogenous mixture of finely divided particles has a particle size distribution such that about 90% of the particles have a diameter of less than 15 microns.