Pharmaceutical composition 271

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;   (b) polyglycolised glycerides;   (c) polyethylene glycols (PEGs); and   (d) hard fats;   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.   
     
     
         2 . A pharmaceutical composition according to  claim 1 , wherein the carrier matrix consists essentially of one or more groups selected from the following groups:
 a. d-alpha-tocopheryl polyethylene glycol 1000 succinate;   b. polyglycolised glycerides; and   c. polyethylene glycols.   
     
     
         3 . A pharmaceutical composition according to  claim 2 , wherein the carrier matrix consists essentially of one or both of the following:
 a. d-alpha-tocopheryl polyethylene glycol 1000 succinate; and   b. polyglycolised glycerides.   
     
     
         4 . A pharmaceutical composition according to  claim 1 , wherein the carrier matrix is d-alpha-tocopheryl polyethylene glycol 1000 succinate or Lauroyl Macrogol-32 Glycerides. 
     
     
         5 . A pharmaceutical composition according to  claim 1 , 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 is present in an amount to make up approximately 30-55% by weight of the carrier matrix component of the composition. 
     
     
         6 . A pharmaceutical composition according to  claim 1 , wherein the carrier matrix is d-alpha-tocopheryl polyethylene glycol 1000 succinate. 
     
     
         7 . A pharmaceutical composition according to  claim 6 , 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. 
     
     
         8 . A pharmaceutical composition according to  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. 
     
     
         9 . 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. 
     
     
         10 . A pharmaceutical composition according to  claim 1 , wherein the composition is semi-solid or solid at ambient temperature. 
     
     
         11 . 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. 
     
     
         12 . 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 Vitamin E TPGS;   
       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 , 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 Vitamin E TPGS;   
       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. 
     
     
         14 . 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 Vitamin E TPGS;   
       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. 
     
     
         15 . A pharmaceutical composition according to  claim 1 , wherein the composition is an oral capsule composition. 
     
     
         16 . A process for the preparation of a pharmaceutical composition according to  claim 1  comprising the steps of:
 a. Mixing and melting the components of the carrier matrix; 
 b. Mixing the Agent into the carrier matrix in order to obtain a homogenous mixture; and 
 c. Filling the product of step (b) into a capsule and allowing the mixture to cool to form a viscous liquid, semi-solid or solid mass within the capsule. 
 
     
     
         17 . A method for treating a warm blooded animal (preferably a human) suffering from a condition treatable by the hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide comprising administering thereto a pharmaceutical composition according to  claim 1 . 
     
     
         18 . A method for treating cancer in a warm blooded animal (preferably a human) comprising administering thereto a pharmaceutical composition according to  claim 1 . 
     
     
         19 . (canceled) 
     
     
         20 . (canceled)