Pharmaceutical Formulations Comprising CCR3 Antagonists

Abstract

The present invention relates to pharmaceutical compositions containing one or more compounds of formula 1 wherein R 1 is H, C 1-6 -alkyl, C 0-4 -alkyl-C 3-6 -cycloalkyl, C 1-6 -haloalkyl; R 2 is H, C 1-6 -alkyl; X is an anion selected from the group consisting of chloride or ½ dibenzoyltartrate; j is 1 or 2; and processes for the preparation thereof, and their use to treat diseases connected with the CCR3 receptor.

What is claimed is: 
     
         1 . A pharmaceutical composition comprising as an active ingredient one or more compounds of formula 1 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is H, C 1-6 -alkyl, C 1-6 -alkyl-C 3-6 -cycloalkyl, C 1-6 -haloalkyl; 
         R 2  is H, C 1-6 -alkyl; 
         X is an anion selected from the group consisting of chloride or dibenzoyltartrate 
         j is 1 or 2, 
         a first diluent, a second diluent, a binder, a disintegrant and a lubricant. 
       
     
     
         2 . The pharmaceutical composition of  claim 1  wherein
 R 1  is H, Methyl; 
 R 2  is H, Methyl; 
 X is an anion selected from the group consisting of chloride or dibenzoyltartrate; 
 j is I or 2. 
 
     
     
         3 . The pharmaceutical composition according to  claim 1 , wherein X is chloride and j is 2. 
     
     
         4 . The pharmaceutical composition according to  claim 1 , comprising an additional disintegrant. 
     
     
         5 . The pharmaceutical composition according to  claim 1 , comprising a glidant. 
     
     
         6 . The pharmaceutical composition according to  claim 1 , wherein the diluent is cellulose powder, dibasic calciumphosphate anhydrous, dibasic calciumphosphate dihydrate, erythritol, low substituted hydroxypropyl cellulose, mannitol, pregelatinized starch or xylitol, 
     
     
         7 . The pharmaceutical composition according to  claim 1 , wherein the lubricant is talc, polyethyleneglycol, calcium behenate, calcium stearate, hydrogenated castor oil or magnesium stearate. 
     
     
         8 . The pharmaceutical composition according to  claim 1 , wherein the binder is copovidone (copolymerisates of vinylpyrrolidon with other vinylderivates), hydroxypropyl methylcellulose (HPMC), hydroxypropylcellulose (HPC) or polyvinylpyrrolidon (Povidone). 
     
     
         9 . The pharmaceutical composition according to  claim 1 , wherein the disintegrant is crosscarmelose sodium. 
     
     
         10 . The pharmaceutical composition according to  claim 5 , wherein the glidant is colloidal silicon dioxide. 
     
     
         11 . The pharmaceutical composition according to  claim 1  comprising 
       
         
           
                 
                 
               
                     
                 
                   10-90%  
                   active ingredient 
                 
                   5-70% 
                   diluent 1, 
                 
                   5-30% 
                   diluent 2, 
                 
                   0-30% 
                   binder, 
                 
                   1-12% 
                   disintegrant, and 
                 
                   0.1-3%  
                   lubricant 
                 
                     
                 
             
                
               
               
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         12 . The pharmaceutical composition according to  claim 1  comprising 
       
         
           
                 
                 
               
                     
                 
                   30-70%  
                   active ingredient 
                 
                   10-75%  
                   diluent 1, 
                 
                   5-30% 
                   diluent 2, 
                 
                   0-30% 
                   binder, 
                 
                   0.5-20%     
                   buffering agent, 
                 
                   1-12% 
                   disintegrant, and 
                 
                   0.1-3%  
                   lubricant 
                 
                     
                 
             
                
               
               
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         13 . The pharmaceutical composition according to  claim 4 , wherein the additional disintegrant is crospovidone. 
     
     
         14 . A pharmaceutical composition according to  claim 1  in the dosage form of a capsule, a tablet or a film-coated tablet. 
     
     
         15 . The pharmaceutical composition of  claim 14  comprising 2-4% film coat. 
     
     
         16 . The pharmaceutical composition according to  claim 15  wherein the film coat comprises a film-forming agent, a plasticizer, a glidant and optionally one or more pigments. 
     
     
         17 . The pharmaceutical composition of  claim 16  wherein the film coat comprises Polyvinyl alcohol (PVA) or hydroxypropylmethylcellulose (HPMC), polyethylene glycol (PEG), talc, titanium dioxide and iron oxide.