Composition comprising a benzimidazole and process for its manufacture

Abstract

The invention provides new benzimidazole compositions, comprising: (a) a core containing said benzimidazole active ingredient; (b) an intermediate layer; and (c) an enteric layer; said core being substantially free of binder. The invention also provides a process for manufacturing the composition of the invention.

1 . A composition comprising a benzimidazole active ingredient, said composition comprising: 
 (a) a core containing said benzimidazole active ingredient;    (b) an intermediate layer; and    (c) an enteric layer;    said core being substantially free of binder.    
     
     
         2 . A composition comprising a benzimidazole active ingredient, said composition comprising: 
 (a) a core containing said benzimidazole active ingredient;    (b) an intermediate layer; and    (c) an enteric layer;    said core being substantially free of PVP and of HPMC.    
     
     
         3 . A composition comprising a benzimidazole active ingredient, said composition comprising: 
 (a) a core containing said benzimidazole active ingredient, where said core consists essentially of, by weight: 
 about 10 to about 80 parts of said benzimidazole active ingredient,  
 about 20 to about 85 parts of a first, water-soluble, diluent,  
 about 0 to about 80 parts of a second, water-insoluble, diluent,  
 about 10 to about 40 parts of a disintegrant; and  
 0 to about 5 parts of a lubricant;  
   (b) an intermediate layer; and    (c) an enteric layer.    
     
     
         4 . The composition of  claim 3 , in which said core consists essentially of, by weight: 
 (a) a core containing said benzimidazole active ingredient, where said core consists essentially of, by weight: 
 about 15 to about 60 parts of said benzimidazole active ingredient,  
 about 40 to about 75 parts of a first, water-soluble, diluent,  
 about 0 to about 40 parts of a second, water-insoluble, diluent,  
 about 15 to about 30 parts of a disintegrant; and  
 about 0.5 to about 5 parts of a lubricant;  
   (b) an intermediate layer; and    (c) an enteric layer.    
     
     
         5 . The composition of  claim 3 , comprising a first diluent and a second diluent and in which the weight ratio first diluent to second diluent is from about 1.5:1 to 1:1.5.  
     
     
         6 . The composition of  claim 3 , in which said first, water-soluble, diluent is lactose and said second, water-insoluble, diluent if present is cellulose acetate.  
     
     
         7 . The composition of  claim 3 , in which said disintegrant is cross-linked polyvinylpyrrolidone.  
     
     
         8 . The composition of  claim 3 , in which said lubricant is selected from the group consisting of sodium stearylfumarate, magnesium stearate, talc, glyceryl behenate and their mixtures.  
     
     
         9 . A composition comprising a benzimidazole active ingredient, said composition comprising: 
 (a) a core containing said benzimidazole active ingredient, where said core consists essentially of, by weight: 
 about 15 to about 60 parts of said benzimidazole active ingredient,  
 about 40 to about 75 parts of lactose,  
 about 15 to about 30 parts of a disintegrant, and  
 about 0.5 to about 5 parts of a lubricant;  
   (b) an intermediate layer; and    (c) an enteric layer.    
     
     
         10 . The composition of  claim 9 , in which said disintegrant is cross-linked polyvinylpyrrolidone.  
     
     
         11 . The composition of  claim 9 , in which said lubricant is selected from the group consisting of sodium stearylfumarate, magnesium stearate, talc, glyceryl behenate and their mixtures.  
     
     
         12 . The composition of  claim 3 , in which said core is substantially free of PVP and of HPMC.  
     
     
         13 . The composition of  claim 9 , in which said core is substantially free of PVP and of HPMC.  
     
     
         14 . The composition of  claim 1 , in which said benzimidazole active ingredient is selected from the group consisting of omeprazole, esomeprazole, pantoprazole, lansoprazole, leminoprazole, pariprazole, rabeprazole, timoprazole, aripiprazole and diapiprazole.  
     
     
         15 . The composition of  claim 2 , in which said benzimidazole active ingredient is selected from the group consisting of omeprazole, esomeprazole, pantoprazole, lansoprazole, leminoprazole, pariprazole, rabeprazole, timoprazole, aripiprazole and diapiprazole.  
     
     
         16 . The composition of  claim 3 , in which said benzimidazole active ingredient is selected from the group consisting of omeprazole, esomeprazole, pantoprazole, lansoprazole, leminoprazole, pariprazole, rabeprazole, timoprazole, aripiprazole and diapiprazole.  
     
     
         17 . The composition of  claim 9 , in which said benzimidazole active ingredient is selected from the group consisting of omeprazole, esomeprazole, pantoprazole, lansoprazole, leminoprazole, pariprazole, rabeprazole, timoprazole, aripiprazole and diapiprazole.  
     
     
         18 . The composition of  claim 1 , in which said benzimidazole active ingredient is not in the form of an alkaline salt, and said composition being exempt of alkaline-reacting compounds.  
     
     
         19 . The composition of  claim 2 , in which said benzimidazole active ingredient is not in the form of an alkaline salt, and said composition being exempt of alkaline-reacting compounds.  
     
     
         20 . The composition of  claim 3 , in which said benzimidazole active ingredient is not in the form of an alkaline salt, and said composition being exempt of alkaline-reacting compounds.  
     
     
         21 . The composition of  claim 9 , in which said benzimidazole active ingredient is not in the form of an alkaline salt, and said composition being exempt of alkaline-reacting compounds.  
     
     
         22 . A composition comprising a benzimidazole active ingredient not being in the form of an alkaline salt, said composition being exempt of alkaline-reacting compounds, said composition comprising: 
 (a) a core containing said benzimidazole active ingredient, where said core consists essentially of, by weight: 
 about 15 to about 60 parts of said benzimidazole active ingredient,  
 about 40 to about 75 parts of a first, water-soluble, diluent,  
 about 0 to about 40 parts of a second, water-insoluble, diluent,  
 about 15 to about 30 parts of a disintegrant, and  
 about 0.5 to about 5 parts of a lubricant;  
   (b) an intermediate layer; and    (c) an enteric layer.    
     
     
         23 . The composition of  claim 22 , in which said benzimidazole active ingredient is selected from the group consisting of omeprazole, esomeprazole, pantoprazole, lansoprazole, leminoprazole, pariprazole, rabeprazole, timoprazole, aripiprazole and diapiprazole.  
     
     
         24 . A composition comprising omeprazole, said composition comprising: 
 (a) a core containing said omeprazole, where said core consists essentially of, by weight: 
 about 15 to about 60 parts of said omeprazole,  
 about 40 to about 75 parts of lactose,  
 about 15 to about 30 parts of a disintegrant, and  
 about 0.5 to about 5 parts of a lubricant;  
   (b) an intermediate layer; and    (c) an enteric layer.    
     
     
         25 . A composition comprising esomeprazole, said composition comprising: 
 (a) a core containing said esomeprazole, where said core consists essentially of, by weight: 
 about 15 to about 60 parts of said esomeprazole,  
 about 40 to about 75 parts of lactose,  
 about 15 to about 30 parts of a disintegrant, and  
 about 0.5 to about 5 parts of a lubricant;  
   (b) an intermediate layer; and    (c) an enteric layer.    
     
     
         26 . A composition comprising pantoprazole, said composition comprising: 
 (a) a core containing said pantoprazole, where said core consists essentially of, by weight: 
 about 15 to about 60 parts of said pantoprazole,  
 about 40 to about 75 parts of lactose,  
 about 15 to about 30 parts of a disintegrant, and  
 about 0.5 to about 5 parts of a lubricant;  
   (b) an intermediate layer; and    (c) an enteric layer.    
     
     
         27 . A composition comprising lansoprazole, said composition comprising: 
 (a) a core containing said lansoprazole, where said core consists essentially of, by weight: 
 about 15 to about 60 parts of said lansoprazole,  
 about 40 to about 75 parts of lactose,  
 about 15 to about 30 parts of a disintegrant, and  
 about 0.5 to about 5 parts of a lubricant;  
   (b) an intermediate layer; and    (c) an enteric layer.    
     
     
         28 . A composition comprising rabeprazole, said composition comprising: 
 (a) a core containing said rabeprazole, where said core consists essentially of, by weight: 
 about 15 to about 60 parts of said rabeprazole,  
 about 40 to about 75 parts of lactose,  
 about 15 to about 30 parts of a disintegrant, and  
 about 0.5 to about 5 parts of a lubricant;  
   (b) an intermediate layer; and    (c) an enteric layer.    
     
     
         29 . The composition according to  claim 1 , provided either in a single tablet form or in the form of micro-tablets enclosed inside a capsule.  
     
     
         30 . The composition according to  claim 2 , provided either in a single tablet form or in the form of micro-tablets enclosed inside a capsule.  
     
     
         31 . The composition according to  claim 3 , provided either in a single tablet form or in the form of micro-tablets enclosed inside a capsule.  
     
     
         32 . The composition according to  claim 9 , provided either in a single tablet form or in the form of micro-tablets enclosed inside a capsule.  
     
     
         33 . The composition according to  claim 22 , provided either in a single tablet form or in the form of micro-tablets enclosed inside a capsule.  
     
     
         34 . The composition according to  claim 24 , provided either in a single tablet form or in the form of micro-tablets enclosed inside a capsule.  
     
     
         35 . The composition according to  claim 25 , provided either in a single tablet form or in the form of micro-tablets enclosed inside a capsule.  
     
     
         36 . The composition according to  claim 26 , provided either in a single tablet form or in the form of micro-tablets enclosed inside a capsule.  
     
     
         37 . The composition according to  claim 27 , provided either in a single tablet form or in the form of micro-tablets enclosed inside a capsule.  
     
     
         38 . The composition according to  claim 28 , provided either in a single tablet form or in the form of micro-tablets enclosed inside a capsule.  
     
     
         39 . A process for preparing a composition comprising a benzimidazole active ingredient, said composition comprising: 
 (a) a core containing said benzimidazole active ingredient, where said core consists essentially of, by weight: 
 about 10 to about 80 parts of said benzimidazole active ingredient,  
 about 20 to about 85 parts of a first, water-soluble, diluent,  
 about 0 to about 80 parts of a second, water-insoluble, diluent,  
 about 10 to about 40 parts of a disintegrant; and  
 0 to about 5 parts of a lubricant;  
   (b) an intermediate layer; and    (c) an enteric layer;    said process comprising the steps of 
 (i) granulating said active ingredient with said diluents, said disintegrant and said lubricant if any;  
 (ii) compressing the product of step (i) to form a tablet core containing an active ingredient;  
 (iii) coating said core with said intermediate layer; and  
 (iv) coating a product from step (iii) with said enteric layer.  
   
     
     
         40 . The process according to  claim 39 , in which step (i) is wet granulation.  
     
     
         41 . The process according to  claim 39 , in which step (i) comprises the following sub-steps: 
 (a) dry mixing said benzimidazole active ingredient, said first diluent and optionally said second diluent and optionally part of said disintegrant;    (b) granulating the product of sub-step (a) with water;    (c) drying the granulates of sub-step (b);    (d) dry mixing the dried granulates of sub-step (c) with said disintegrant or the remainder thereof and said lubricant, if any.    
     
     
         42 . A process for preparing a composition comprising a benzimidazole active ingredient, said composition comprising: 
 (a) a core containing said benzimidazole active ingredient, where said core consists essentially of, by weight: 
 about 15 to about 60 parts of said benzimidazole active ingredient,  
 about 40 to about 75 parts of lactose,  
 about 15 to about 30 parts of a disintegrant, and  
 about 0.5 to about 5 parts of a lubricant;  
   (b) an intermediate layer; and    (c) an enteric layer;    said process comprising the steps of 
 (i) granulating said active ingredient with said lactose, said cellulose acetate, said disintegrant and said lubricant;  
 (ii) compressing the product of step (i) to form a tablet core containing an active ingredient;  
 (iii) coating said core with said intermediate layer; and  
 (iv) coating a product from step (iii) with said enteric layer.  
   
     
     
         43 . The process according to  claim 42 , in which step (i) is wet granulation.  
     
     
         44 . The process according to  claim 42 , in which step (i) comprises the following sub-steps: 
 (a) dry mixing said benzimidazole active ingredient, said lactose and optionally part of said disintegrant;    (b) granulating the product of sub-step (a) with water;    (c) drying the granulates of sub-step (b);    (d) dry mixing the dried granulates of sub-step (c) with said disintegrant or the remainder thereof and said lubricant.