Dpp iv inhibitor formulations

Abstract

The present invention relates to pharmaceutical compositions of DPP IV inhibitors with an amino group, their preparation and their use to treat diabetes mellitus.

1 . A pharmaceutical composition comprising as an active ingredient a DPP IV inhibitor compound with an amino group or a salt thereof, a first diluent, a second diluent, a binder, a disintegrant and a lubricant. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the first and second diluents are independently cellulose powder, dibasic calciumphosphate anhydrous, dibasic calciumphosphate dihydrate, erythritol, low substituted hydroxypropyl cellulose, mannitol, pregelatinized starch, or xylitol, 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the lubricant is talc, polyethyleneglycol, calcium behenate, calcium stearate, hydrogenated castor oil, or Magnesium stearate. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the binder is copovidone (copolymerisates of vinylpyrrolidon with other vinylderivates), hydroxypropyl methylcellulose (HPMC), hydroxypropylcellulose (HPC), or polyvinylpyrrolidon (Povidone). 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the disintegrant is corn starch. 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein the first diluent is mannitol, the second diluent is pregelatinized starch, the binder is copovidone, the disintegrant is corn starch, and the lubricant is magnesium stearate. 
     
     
         7 . The pharmaceutical composition of  claim 1  further comprising an additional disintegrant. 
     
     
         8 . The pharmaceutical composition of  claim 7 , wherein the additional disintegrant is crospovidone. 
     
     
         9 . The pharmaceutical composition of  claim 1  further comprising a glidant. 
     
     
         10 . The pharmaceutical composition of  claim 9 , wherein the glidant is colloidal silicon dioxide. 
     
     
         11 . The pharmaceutical composition of  claim 1  comprising 
       
         
           
                 
                 
               
                     
                 
                   0.5-20%  
                   active ingredient 
                 
                   40-88% 
                   diluent 1, 
                 
                    3-40% 
                   diluent 2, 
                 
                   1-5% 
                   binder, 
                 
                    5-15% 
                   disintegrant, and 
                 
                   0.1-4%   
                   lubricant. 
                 
                     
                 
             
                
               
               
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         12 . The pharmaceutical composition of  claim 1  comprising 
       
         
           
                 
                 
               
                     
                 
                   0.5-7%   
                   active ingredient 
                 
                   50-75% 
                   diluent 1, 
                 
                    5-15% 
                   diluent 2, 
                 
                   2-4% 
                   binder, 
                 
                    8-12% 
                   disintegrant, and 
                 
                   0.5-2%   
                   lubricant 
                 
                     
                 
             
                
               
               
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         13 . The pharmaceutical composition according to  claim 1  in the dosage form of a capsule, a tablet, or a film-coated tablet. 
     
     
         14 . The pharmaceutical composition of  claim 13  comprising 2-4% film coat. 
     
     
         15 . The pharmaceutical composition of  claim 1 , wherein the film coat comprises a film-forming agent, a plasticizer, a glidant and optionally one or more pigments. 
     
     
         16 . The pharmaceutical composition of  claim 15 , wherein the film coat comprises hydroxypropylmethylcellulose (HPMC), polyethylene glycol (PEG), talc, titanium dioxide and iron oxide. 
     
     
         17 . A process for the preparation of a pharmaceutical composition according to  claim 1  comprising
 a. dissolving a binder in a solvent to produce a granulation liquid;   b. blending a DPP-IV inhibitor, a diluent, and a disintegrant to produce a pre-mix;   c. moistening the pre-mix with the granulation liquid and subsequently granulating the moistened pre-mix;   d. optionally sieving the granulated pre-mix through a sieve with a mesh size of at least 1.0 mm;   e. drying the granulate at about 40-75° C. until the desired loss on drying value in the range of 1-5% is obtained;   f. sieving the dried granulate through a sieve with a mesh size of at least 0.6 mm;   g. adding lubricant to the granulate for final blending.   
     
     
         18 . The process according to  claim 17  further comprising
 h. compressing the final blend into tablet cores;   i. preparing a coating suspension;   j. coating the tablet cores with the coating suspension to a weight gain of about 2-4% to produce film-coated tablets.   
     
     
         19 . The process according to  claim 17 , wherein part of the exipients are added extragranular prior to the final blending of step g. 
     
     
         20 . The process according to  claim 17 , wherein the granulate produced in steps a-e is produced in a one pot high shear granulation process and subsequent drying in a one pot granulator.