PHARMACEUTICAL COMPOSITION 271
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; 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.
2 . (canceled)
3 . (canceled)
4 . A pharmaceutical composition according to claim 1 , wherein the polyglycolised glycerides is Lauroyl Macrogol-32 Glycerides.
5 . A pharmaceutical composition according to claim 4 , 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 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 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 , 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.
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 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.
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 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 comprising administering thereto a pharmaceutical composition according to claim 1 .
19 . (canceled)
20 . (canceled)