IP Library › Patent Application 16023102
Patent Application
App. No. 16/023,102

PHARMACEUTICAL COMPOSITION

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Patent No.
US None
App. No.
16/023,102
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.

Claims (47)

1 - 38 . (canceled)

39 . 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);

(b) polyglycolised glycerides; and

(c) polyethylene glycols;

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.

40 . The pharmaceutical composition according to claim 39 , wherein the carrier matrix consists essentially of one or both of the following:

(a) d-alpha-tocopher polyethylene glycol 1000 succinate; and

(b) polyglycolised glycerides.

41 . The pharmaceutical composition according to claim 39 , wherein the carrier matrix is d-alpha-tocopheryl polyethylene glycol 1000 succinate or Lauroyl Macrogol-32 Glycerides.

42 . The pharmaceutical composition according to claim 39 , 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.

43 . The pharmaceutical composition according to claim 39 , wherein the carrier matrix is d-alpha-tocopheryl polyethylene glycol 1000 succinate.

44 . The pharmaceutical composition according to claim 43 , 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.

45 . The pharmaceutical composition according to claim 39 , 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.

46 . The pharmaceutical composition according to claim 39 , 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.

47 . The pharmaceutical composition according to claim 39 , wherein the composition is semi-solid or solid at ambient temperature.

48 . The pharmaceutical composition according to claim 39 , 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.

49 . The pharmaceutical composition according to claim 39 , 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 (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.

50 . The pharmaceutical composition according to claim 39 , 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 (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.

51 . The pharmaceutical composition according to claim 39 , 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 (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.

52 . The pharmaceutical composition according to claim 39 , wherein the composition contains 30.25+/−2 mg 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.

53 . The pharmaceutical composition according to claim 39 , wherein the composition contains 12.1+/−2 mg 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.

54 . The pharmaceutical composition according to claim 39 , wherein the composition is an oral capsule composition.

55 . A process for the preparation of a pharmaceutical composition according to claim 39 comprising the steps of:

(a) Mixing and melting the components of the carrier matrix;

(b) Mixing 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 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.

56 . A method of treating a condition treatable with a 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 a pharmaceutical composition according to claim 39 to a subject in need thereof.

57 . The method of claim 56 , wherein the condition is cancer.

58 . The method of claim 57 , wherein the cancer is malignant melanoma, brain, lung, squamous cell, bladder, gastric, pancreatic, breast, head, neck, renal, kidney, ovarian, prostate, colorectal, esophageal, testicular, gynecological or thyroid cancer.

59 . The method of claim 57 , wherein the cancer is lung cancer.

60 . The method of claim 57 , wherein the cancer thyroid cancer.

61 . The method of claim 57 , wherein the cancer malignant melanoma.

62 . The method of claim 57 , further comprising administering the composition in combination with taxotere.

63 . The method of claim 57 , further comprising administering the composition in combination with an alkylating agent.