Barium salt of benzimidazole derivative

Abstract

The invention relates to crystalline barium salt of (S)-omeprazole, which is (S)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)-methyl]sulfinyl]-1H-benzimidazole. The invention also relates to processes for preparing crystalline barium salt of (S)-omeprazole and pharmaceutical compositions that include the crystalline barium salt of (S)-omeprazole so prepared.

1 . Crystalline barium salt of (S)-omeprazole prepared by using a process comprising the step of contacting (S)-omeprazole freebase, or its salt, with a barium containing compound that is capable of forming the barium salt (S)-omeprazole in a solvent, provided that a base is used when (S)-omeprazole base is used as the starting material, wherein the solvent comprises ketones, alcohols, esters, cyclic ethers, chlorinated hydrocarbons, nitriles, dipolar aprotic solvents, and mixtures thereof. 
     
     
         2 . The crystalline barium salt of (S)-omeprazole according to  claim 1 , wherein the barium containing compound is the barium salt of an inorganic acid. 
     
     
         3 . The crystalline barium salt of (S)-omeprazole according to  claim 2 , wherein the barium salt is selected from the group consisting of barium chloride, barium nitrate, barium phosphate, barium carbonate, and barium sulfate. 
     
     
         4 . The crystalline barium salt of (S)-omeprazole according to  claim 1 , wherein the barium salt of an organic acid is used. 
     
     
         5 . The crystalline barium salt of (S)-omeprazole according to  claim 4 , wherein the barium salt is selected from the group consisting of barium oxalate, barium acetate, barium lactate, barium succinate, barium citrate, and barium tartrate. 
     
     
         6 . The crystalline barium salt of (S)-omeprazole according to  claim 1 , wherein the base is selected from the group consisting of alkali metal hydroxides, alkali metal carbonates, alkali metal bicarbonates and ammonium hydroxide. 
     
     
         7 . The crystalline barium salt of (S)-omeprazole according to  claim 6 , wherein the base is selected from the group consisting of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and sodium bicarbonate. 
     
     
         8 . The crystalline barium salt of (S)-omeprazole according to  claim 1 , wherein the solvent is selected from the group consisting of acetone, methanol and mixtures thereof. 
     
     
         9 . The crystalline barium salt of (S)-omeprazole according to  1 , wherein the solvent has been removed from the crystalline barium salt of (S)-omeprazole. 
     
     
         10 . The crystalline barium salt of (S)-omeprazole according to  claim 9 , wherein the solvent has been removed by vacuum distillation or spray drying. 
     
     
         11 . The crystalline barium salt of (S)-omeprazole according to  claim 1 , wherein the crystalline barium salt of (S)-omeprazole is present in a pharmaceutical composition. 
     
     
         12 . The crystalline barium salt of (S)-omeprazole according to  claim 11 , wherein the pharmaceutical composition further comprises an additional therapeutic agent with the crystalline barium salt of (S)-omeprazole. 
     
     
         13 . The crystalline barium salt of (S)-omeprazole according to  claim 12 , wherein the pharmaceutical composition is in the form of a tablet, capsule, suspension, dispersion, or injectable. 
     
     
         14 . The crystalline barium salt of (S)-omeprazole according to  claim 12 , wherein the pharmaceutical composition is in the form of a capsule or injectable. 
     
     
         15 . A pharmaceutical composition comprising a crystalline barium salt of (S)-omeprazole and an additional therapeutic agent. 
     
     
         16 . The pharmaceutical composition according to  claim 15 , wherein the pharmaceutical composition is in the form of a tablet, capsule, suspension, dispersion, or injectable. 
     
     
         17 . The pharmaceutical composition according to  claim 15 , wherein the pharmaceutical composition is in the form of a capsule or injectable. 
     
     
         18 . A pharmaceutical composition comprising a crystalline barium salt of (S)-omeprazole and an additional therapeutic agent, wherein the crystalline barium salt of (S)-omeprazole is prepared by using a process comprising the step of contacting (S)-omeprazole freebase, or its salt, with a barium containing compound that is capable of forming the barium salt (S)-omeprazole in a solvent, provided that a base is used when (S)-omeprazole base is used as the starting material, wherein the solvent comprises ketones, alcohols, esters, cyclic ethers, chlorinated hydrocarbons, nitriles, dipolar aprotic solvents, and mixtures thereof. 
     
     
         19 . The pharmaceutical composition according to  claim 18 , wherein the pharmaceutical composition is in the form of a tablet, capsule, suspension, dispersion, or injectable. 
     
     
         20 . The pharmaceutical composition according to  claim 18 , wherein the pharmaceutical composition is in the form of a capsule or injectable.