Crystalline form of omeprazole

Abstract

A novel crystalline form of the substrate known under the chemical name 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfiny] -1H-benzimidazole, and having the generic name omeprazole, hereinafter referred to as omeprozole form C, is disclosed. Further, a process for the preparation of omeprazole form C, a pharmaceutical formulation containing omeprazole form C in admixture with pharmaceutically acceptable excipients and the use of omeprazole form C for treatment of gastrointestinal disorders are disclosed.

1 . Omeprazole form C, characterized in providing an X-ray powder diffraction pattern exhibiting substantially the following d-values:  
       
         
           
                 
                 
               
                     
                 
                     
                 
                   d-values 
                     
                 
                   (Å) 
                   Relative intensity 
                 
                     
                 
                   9.5-9.6 
                   very strong 
                 
                   7.9-8.0 
                   strong 
                 
                   7.4-7.5 
                   weak 
                 
                   7.2 
                   very strong 
                 
                   5.9-6.0 
                   medium 
                 
                   5.6 
                   medium 
                 
                   5.1-5.2 
                   very strong 
                 
                   4.88-4.90 
                   weak 
                 
                   4.81-4.84 
                   weak 
                 
                   4.65-4.67 
                   medium 
                 
                   4.57-4.60 
                   medium 
                 
                   4.48-4.51 
                   strong 
                 
                   4.34-4.36 
                   medium 
                 
                   4.16-4.19 
                   weak 
                 
                   3.94-3.97 
                   weak 
                 
                   3.72-3.73 
                   strong 
                 
                   3.58-3.59 
                   medium 
                 
                   3.46-3.47 
                   strong 
                 
                   3.29-3.30 
                   medium 
                 
                   3.23-3.25 
                   strong 
                 
                   3.19-3.20 
                   medium 
                 
                   3.11-3.12 
                   weak 
                 
                   3.03-3.04 
                   weak 
                 
                     
                 
                     
                 
             
                
                
                
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         2 . Omeprazole form C, according to  claim 1 , characterized by having the following unit cell parameters: 
 a=9.705-9.740 Å, b=10.335-10.375 Å, c=10.525-10.590 Å, α=90.95-91.15°, β=111.70-111.90°, γ=116.25-116.50°.    
     
     
         3 . Omeprazole form C, characterized in comprising characteristic absorption bands by Fourier Transform Infrared Spectroscopy at the wavelengths 1204 cm −1 , 1076 cm −1 , 1024 cm −1 , 1014 cm −1  and 822 cm −1 .  
     
     
         4 . A process for the preparation of omeprazole form C as defined in  claim 1  or  3 , comprising the following steps: 
 a) dissolving crude omeprazole in a solvent or a mixture of solvents in which omeprazole is freely soluble, and  
 b) precipitating omeprazole form C with a solvent in which omeprazole is poorly soluble.  
 
     
     
         5 . A process for the preparation of omeprazole form C according to  claim 4 , characterized in that dissolving of omeprazole is carried out in a solvent or a mixture of solvent chosen from the group consisting of: 40% aqueous methylamine; a mixture of 40% aqueous methylamine with dichloromethane, chloroform or acetone; a mixture of 25% ammonia with dichloromethane, chloroform or acetone; and a mixture of triethylamine with dichloromethane or chloroform.  
     
     
         6 . A process for the preparation of omeprazole form C according to  claim 4 , characterized in that dissolving of crude omeprazole is carried out in a mixture of 40% aqueous methylamine and acetone.  
     
     
         7 . A process for the preparation of omeprazole form C according to  claim 4 , characterized in that dissolving of crude omeprazole is carried out at room temperature.  
     
     
         8 . A process for the preparation of omeprazole form C according to  claim 4 , characterized in that precipitation of omeprazole form C is carried out in acetone.  
     
     
         9 . A process for the preparation of omeprazole form C according to  claim 4 , characterized in that omeprazole form C contains less than 200 μg/g of acetone as a residual solvent.  
     
     
         10 . A process for the preparation of omeprazole form C according to  claim 9 , characterized in that omeprazole form C contains less than 100 μg/g of acetone as a residual solvent.  
     
     
         11 . A process for the preparation of omeprazole form C according to  claim 4 , characterized in that precipitation of omeprazole form C is carried out at room temperature.  
     
     
         12 . A process for the preparation of omeprazole form C according to  claim 4  further comprising cooling crystal suspension before filtration to a temperature in the range of −10 to −20° C.  
     
     
         13 . A pharmaceutical formulation comprising a therapeutically effective amount of the active substance omeprazole form C as defined in  claim 1  or  3  in admixture with a pharmaceutically acceptable excipient.  
     
     
         14 . The use of omeprazole form C as defined in  claim 1  or  3  for the preparation of a medicament for the treatment of gastrointestinal disease.  
     
     
         15 . A method of treatment of a gastrointestinal disease by administering a pharmaceutical formulation comprising a therapeutically effective amount of the active substance omeprazole form C, as defined in  claim 1  or  3 , in admixture with a pharmaceutically acceptable excipient, to a patient suffering from gastrointestinal disease.