Crystalline form of omeprazole

Abstract

The present invention relates to a novel crystalline form of 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole, known under the generic name omeprazole. Further, the present invention also relates to the use of the novel crystalline form of 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole for the treatment of gastrointestinal disorders, pharmaceutical compositions containing it as well as processes for the preparation of the novel crystalline form of 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole.

1 . Omeprazole form A, characterized in being thermodynamically stable at room temperature.  
     
     
         2 . Omeprazole form A, characterized in being essentially non-hygroscopic.  
     
     
         3 . Omeprazole form A according to claims  1  or  2 , characterized in providing an X-ray powder diffraction pattern exhibiting substantially the following d-values;  
       
         
           
                 
                 
                 
                 
                 
               
                     
                     
                 
                     
                     
                 
                     
                   Form A 
                     
                   Form A 
                     
                 
                 
                 
                 
                 
                 
               
                     
                   d-value 
                   Relative 
                   d-value 
                   Relative 
                 
                     
                   (Å) 
                   intensity 
                   (Å) 
                   intensity 
                 
                     
                     
                 
                 
                 
                 
                 
                 
               
                     
                   9.5 
                   vs 
                   3.71 
                   s 
                 
                     
                   7.9 
                   s 
                   3.59 
                   m 
                 
                     
                   7.4 
                   w 
                   3.48 
                   m 
                 
                     
                   7.2 
                   vs 
                   3.45 
                   s 
                 
                     
                   6.0 
                   m 
                   3.31 
                   w 
                 
                     
                   5.6 
                   s 
                   3.22 
                   s 
                 
                     
                   5.2 
                   s 
                   3.17 
                   m 
                 
                     
                   5.1 
                   s 
                   3.11 
                   w 
                 
                     
                   4.89 
                   w 
                   3.04 
                   w 
                 
                     
                   4.64 
                   m 
                   3.00 
                   w 
                 
                     
                   4.60 
                   m 
                   2.91 
                   w 
                 
                     
                   4.53 
                   w 
                   2.86 
                   w 
                 
                     
                   4.49 
                   m 
                   2.85 
                   w 
                 
                     
                   4.31 
                   m 
                   2.75 
                   w 
                 
                     
                   4.19 
                   w 
                   2.67 
                   w 
                 
                     
                   4.15 
                   w 
                   2.45 
                   w 
                 
                     
                   3.95 
                   w 
                   2.41 
                   w 
                 
                     
                     
                 
                     
                     
                 
             
                
                
                
               
            
             
                
                
                
               
            
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         4 . Omeprazole form A, according to any of claims  1 - 3 , characterized by having a triclinic unit cell with parameters 
 a=10.410(4) Å, b=10.468(3) Å, c=9.729(4) Å, α=111.51(3)°, β=116.78(3)°, γ=90.77( 3 )°.    
     
     
         5 . Omeprazole, characterized in containing more than 50%, by weight, of omeprazole form A according to any of claims  1 - 4 .  
     
     
         6 . A process for the preparation of omeprazole form A as defined in any of claims  1 -4, comprising the steps of; 
 a) dissolving or suspending omeprazole of any form, or a mixture of any form, in a suitable solvent;    b) allowing the solution to crystallize, optionally using omeprazole form A to induce crystallization, and    c) isolating the omeprazole form A thus obtained.    
     
     
         7 . A process according to  claim 6 , characterized in that the solvent used in step a) is chosen from a group consisting of methanol, ethanol, acetone, ethyl acetate, methyl tert. butyl ether, toluene, or any mixture thereof.  
     
     
         8 . A process according to claims  6  or  7 , characterized in that step a) is performed at 15-25° C.  
     
     
         9 . A process according to any of claims  6 - 8 , characterized in that step b) is performed during a prolonged time period.  
     
     
         10 . A process according to any claim  6 - 9 , characterized in that step b) is performed during at least 2 hours.  
     
     
         11 . Omeprazole form A, prepared by a process according to any of claims  6 - 10 .  
     
     
         12 . A pharmaceutical formulation comprising omeprazole as defined in any of claims  1 - 5  in admixture with a pharmaceutically acceptable excipient.  
     
     
         13 . The use of omeprazole as defined in any of claims  1 - 5 , as active ingredient in the manufacture of medicament for use in treatment of gastrointestinal disorders.  
     
     
         14 . A method of treatment of gastrointestinal disorders which comprises administration of a therapeutically effective amount of omeprazole as defined in any of claims  1 - 5 , to a patient suffering from gastrointestinal disorders.