Pharmaceutical formulation comprising a pyrimidine-a-one derivative coated with an enteric polymer

Abstract

The present invention provides enteric polymer coated tablet formulations for oral administration which comprise a phospholipase A2 enzyme Lipoprotein Associated Phospholipase A2 (Lp-PLA2) inhibitor, processes for preparing such formulations and their use in therapy, in particular the treatment of atherosclerosis.

1 . A pharmaceutical formulation comprising a core which includes a pharmaceutically active material which is a compound of formula (I):  
     
       
         
         
             
             
         
       
     
     wherein: 
 R a  and R b  together are (CH 2 ) n  where n is 3 or 4, to form, with the pyrimidine ring carbon atoms to which they are attached, a fused 5-or 6-membered carbocyclic ring; and  
 R 1  is phenyl optionally substituted by halogen;.  
 R 2  is C (1-3) alkyl substituted by NR 5 R 6 ;  
 R 3  and R 4  form a 4-(4-trifluoromethylphenyl)phenyl moiety; and  
 R 5  and R 6  which may be the same or different is each selected from hydrogen, or C (1-6) alkyl;  
 and a casing which comprises an enteric polymer.  
 
   
   
       2 . A pharmaceutical formulation according to  claim 1  wherein said active ingredient is 1-(N-(2-(Diethylamino)ethyl)-N-(4-(4-trifluoromethylphenyl)benzyl)aminocarbonylmethyl)-2-(4-fluorobenzyl)th 5,6-trimethylenepyrimidin-4-one.  
   
   
       3 . A pharmaceutical formulation according to  claim 1  wherein said core further comprises a disintegrant.  
   
   
       4 . A pharmaceutical formulation according to  claim 3  wherein said disintegrant is croscarmellose sodium.  
   
   
       5 . A pharmaceutical formulation according to  claim 1  wherein said core further comprises a diluent.  
   
   
       6 . A pharmaceutical formulation according to  claim 5  wherein said diluent is lactose.  
   
   
       7 . A pharmaceutical formulation according to  claim 1  wherein said core further comprises a binder.  
   
   
       8 . A pharmaceutical formulation according to  claim 7  wherein said binder is hydroxypropylmethyl cellulose.  
   
   
       9 . A pharmaceutical formulation according to  claim 1  wherein said core comprises microcrystalline cellulose.  
   
   
       10 . A pharmaceutical formulation according to  claim 1  wherein said enteric polymer is a eudragit® enteric polymer.  
   
   
       11 . A pharmaceutical formulation according to  claim 1  wherein said casing further comprises an anti tack agent.  
   
   
       12 . A pharmaceutical formulation according to  claim 1  wherein said casing further comprises a surfactant.  
   
   
       13 . A pharmaceutical formulation according to  claim 1  wherein said active is micronised.  
   
   
       14 . A process for making a pharmaceutical formulation according to  claim 1  comprising wet bead milling.  
   
   
       15 . A pharmaceutical formulation according to  claim 1  for use in the treatment of atherosclerosis.