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.

1 . A pharmaceutical composition comprising 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 a carrier matrix, wherein the carrier matrix consists essentially of one or more pharmaceutically acceptable carriers selected from the following groups:
 (a) d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS); and   (b) polyglycolised glycerides; and   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 carrier matrix; and   wherein the pharmaceutical composition is for oral administration.   
     
     
         2 . A pharmaceutical composition according to  claim 1 , wherein the polyglycolised glycerides are Lauroyl Macrogol-32 Glycerides. 
     
     
         3 . A pharmaceutical composition according to  claim 2 , wherein the carrier matrix is a mixture of d-alpha-tocopheryl polyethylene glycol 1000 succinate and Lauroyl Macrogol-32 Glycerides and wherein the Lauroyl Macrogol-32 Glycerides are present in an amount to make up approximately 30-55% by weight of the carrier matrix component of the composition. 
     
     
         4 . A pharmaceutical composition according to  claim 1 , wherein the carrier matrix is d-alpha-tocopheryl polyethylene glycol 1000 succinate. 
     
     
         5 . A pharmaceutical composition according to  claim 4 , wherein the d-alpha-tocopheryl polyethylene glycol 1000 succinate is present in an amount to make up approximately 65 to 95% by weight of the composition. 
     
     
         6 . A pharmaceutical composition according  claim 1 , wherein greater than 90% by weight of the total amount of the hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide present in the composition is dispersed within the carrier matrix. 
     
     
         7 . A pharmaceutical composition according to  claim 1 , wherein the composition contains between 5 to 30% by weight of the hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide. 
     
     
         8 . A pharmaceutical composition according to  claim 1 , wherein the composition is semi-solid or solid at ambient temperature. 
     
     
         9 . A pharmaceutical composition according to  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 is dispersed in the form of finely divided particles that are distributed throughout the phase comprising the carrier matrix. 
     
     
         10 . A pharmaceutical composition according to  claim 1 , comprising:
 (i) from 15 to 25 parts of 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) from 75 to 85 parts of d-alpha-tocopheryl polyethylene glycol 1000 succinate;   wherein both parts are by weight and the sum of the parts (i)+(ii)=100;   and 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 and the composition is semi-solid or solid at ambient temperature.   
     
     
         11 . A pharmaceutical composition according to  claim 1 , comprising:
 (i) from 18 to 22 parts of 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) from 78 to 82 parts of d-alpha-tocopheryl polyethylene glycol 1000 succinate; wherein both parts are by weight and the sum of the parts (i)+(ii)=100; and 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 and the composition is semi-solid or solid at ambient temperature.   
     
     
         12 . A pharmaceutical composition according to  claim 1 , comprising:
 (i) 19-21 parts of 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) 79-81 parts of d-alpha-tocopheryl polyethylene glycol 1000 succinate; wherein both parts are by weight and the sum of the parts (i)+(ii)=100; and 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 and the composition is semi-solid or solid at ambient temperature.   
     
     
         13 . A pharmaceutical composition according to  claim 1 , wherein the composition is capsule composition.