Methods for stabilizing benzimidazole compounds
The present invention provides a method for stabilizing an oral solid formulation containing a benzimidazole-based compound or a physiologically acceptable salt thereof. That is, it provides a method for stabilizing a benzimidazole-based compound or a physiologically acceptable salt thereof, comprising incorporating 1) a crospovidone or a crospovidone and 2) sodium hydroxide and/or potassium hydroxide to a benzimidazole-based compound or a physiologically acceptable salt thereof.
1. A method for stabilizing a benzimidazole-based compound or a physiologically acceptable salt thereof, comprising incorporating by mixing together (1) a crospovidone, (2) sodium hydroxide, potassium hydroxide or a mixture thereof, and (3) a benzimidazole-based compound represented by the following Formula 1, or a physiologically acceptable salt thereof
wherein Het 1 is
and Het 2 is
R 1 and R 2 are the same as or different from each other and are selected from hydrogen, methoxy and difluoromethoxy; R 3 is selected from hydrogen and sodium; and R 4 , R 5 and R 6 are the same as or different from each other and are selected from hydrogen, methyl, methoxy, methoxypropoxy and trifluoroethoxy
thereby forming a uniform mixture of components (1), (2) and (3);
wherein the benzimidazole-based compound (3) and the crospovidone (1) are incorporated with each other in a weight ratio of 0.5 to 5 part by weight to 1 part by weight of the benzimidazole-based compound and,
wherein the sodium hydroxide or potassium hydroxide or their mixture (2) and the benzimidazole-based compound (3) are incorporated with each other in a weight ratio of 0.01 to 2 parts (2) to one part by weight of the benzimidazole-based compound (3) and,
wherein the crospovidone (1) is present in an amount of more than 10 weight percent of the mixture.
2. A method for preventing a benzimidazole-based compound or a physiologically acceptable salt thereof from changing in color, which comprises incorporating and mixing together (1) a crospovidone, (2) sodium hydroxide, potassium hydroxide or a mixture thereof, and (3) a benzimidazole-based compound represented by the following Formula 1, or a physiologically acceptable salt thereof
wherein Het 1 is
and Het 2 is
R 1 and R 2 are the same as or different from each other and are selected from hydrogen, methoxy and difluoromethoxy; R 3 is selected from hydrogen and sodium; and R 4 , R 5 and R 6 are the same as or different from each other and are selected from hydrogen, methyl, methoxy, methoxypropoxy and trifluoroethoxy
thereby forming a uniform mixture of components (1), (2) and (3);
wherein the benzimidazole-based compound and the crospovidone are incorporated with each other in a weight ratio of 0.5 to 5 part by weight to 1 part by weight of the benzimidazole-based compound and,
wherein the sodium hydroxide or potassium hydroxide or their mixture (2) and the benzimidazole-based compound (3) are incorporated with each other in a weight ratio of 0.01 to 2 parts (2) to one part by weight of the benzimidazole-based compound (3) and,
wherein the crospovidone (1) is present in an amount of more than 10 weight percent of the mixture.