Stable benzimidazole formulation

Abstract

A stable composition with a benzimidazole derivative, such as Omeprazole, which does not contain a separating layer between the active compound and an enteric coating layer. Instead, the enteric coating layer is applied as a solution with a pH value of at least 6.5, and more preferably in a range of from about 7 to about 10, directly to the benzimidazole derivative substrate. This solution, with the optional addition of a plasticizer, can be directly coated onto the substrate without any necessity for an intermediate layer. Furthermore, in this pH range, the enteric coating is optionally applicable in an aqueous solution, thereby obviating the need for organic solvents for dissolving the enteric coating material. The resultant formulation maintains the stability of the benzimidazole derivative during storage and at the same time protects the product during passage through the acidic environment of the stomach.

1 - 17 . (canceled) 
     
     
         18 . A stable composition for oral administration of a benzimidazole derivative, the composition comprising:
 a) a single tablet core comprising a benzimidazole derivative; and   b) an enteric coating on the single tablet core, wherein the enteric coating is formed from an aqueous solution or dispersion comprising an enteric coating material that has been at least about 60% neutralized by an alkaline compound prior to being applied on the single tablet core.   
     
     
         19 . The composition of  claim 18 , wherein the enteric coating material has been at least about 80% neutralized by an alkaline compound. 
     
     
         20 . The composition of  claim 19 , wherein the enteric coating material has been at least about 95% neutralized by an alkaline compound. 
     
     
         21 . The composition of  claim 18 , wherein the aqueous solution or dispersion has a pH value of at least 6.5. 
     
     
         22 . The composition of  claim 21 , wherein the pH value is in a range of from about 7 to about 10. 
     
     
         23 . The composition of  claim 18 , wherein the alkaline compound comprises sodium or potassium hydroxide. 
     
     
         24 . The composition of  claim 18 , wherein the alkaline compound comprises ammonium hydroxide. 
     
     
         25 . The composition of  claim 18 , wherein the benzimidazole derivative is omeprazole or a pharmaceutically acceptable salt thereof. 
     
     
         26 . The composition of  claim 18 , wherein the enteric coating material is selected from the group consisting of hydroxypropyl methylcellulose acetate succinate (HPMCAS), polyvinyl acetate phthalate, cellulose acetate phthalate, cellulose acetate trimellitate, polymethacrylic acid methyl methacrylate and polymethacrylic acid ethyl methacrylate. 
     
     
         27 . The composition of  claim 18 , wherein the enteric coating further comprises a plasticizer. 
     
     
         28 . The composition of  claim 27 , wherein the plasticizer is selected from the group consisting of a citric acid ester and a phthalic acid ester. 
     
     
         29 . The composition of  claim 18 , which is stable when stored under accelerated conditions of 30° C. and 60% relative humidity for at least 1 month. 
     
     
         30 . The composition of  claim 29 , which is stable when stored under accelerated conditions of 30° C. and 60% relative humidity for at least 6 months. 
     
     
         31 . The composition of  claim 18 , which has gastric acid resistance of at least 95% when placed in simulated gastric fluid at pH of about 1 for at least 2 hours. 
     
     
         32 . The composition of  claim 31 , wherein the gastric resistance is maintained after storage under accelerated conditions of 30° C. and 60% relative humidity for 1 month. 
     
     
         33 . The composition of  claim 32 , wherein the gastric resistance is maintained after storage under accelerated conditions of 30° C. and 60% relative humidity for 6 months.