Stabilization of quinapril using magnesium oxide

Abstract

The present invention is directed to ACE inhibitor-containing compositions stabilized by the presence of magnesium oxide. Preferably, the ACE inhibitor, quinapril, is protected from certain forms of degradation when prepared in a pharmaceutical composition consisting essentially of magnesium oxide as the stabilizing agent. The presence of magnesium oxide also lends itself to favorable processing conditions during the manufacture of ACE inhibitor-containing compositions, especially processing by wet granulation.

1 - 2 . (canceled)  
     
     
         3 . A pharmaceutical composition which contains: 
 (a) a compound of Formula I                          wherein A is absent, a fused 5-, 6-, or 7-membered cycloaliphatic ring or a fused benzene ring which is unsubstituted or substituted by 1 or 2 alkoxy groups having 1 to 4 carbon atoms; n is 0 or 1, and R is hydrogen or alkyl having 1 to 5 carbon atoms, or a pharmaceutically acceptable acid addition salt thereof;    (b) a suitable amount of a stabilizer to retard cyclization and discoloration, the stabilizer consisting essentially of magnesium oxide; and    (c) a suitable amount of a saccharide to inhibit hydrolysis.    
     
     
         4 . The composition of  claim 3  wherein A is absent, a fused 5- or 6-membered cycloaliphatic ring or a fused benzene ring which is unsubstituted or substituted by 2 methoxy groups; n is 0 or 1, and R is hydrogen or ethyl, or a pharmaceutically acceptable acid addition salt thereof.  
     
     
         5 . The composition of  claim 3  wherein (a) is quinapril or a pharmaceutically acceptable acid addition salt thereof.  
     
     
         6 . The composition of  claim 3  wherein (a) is quinapril hydrochloride.  
     
     
         7 . The composition of  claim 3  wherein additional stabilizers are present.  
     
     
         8 . The composition of  claim 3  wherein (b) contains about 1% to about 90% magnesium oxide per total weight of the formulation.  
     
     
         9 . The composition of  claim 3  wherein (c) contains at least one of mannitol and lactose.  
     
     
         10 . The composition of  claim 3  wherein the composition also contains at least one material selected from the group consisting of: binders, disintegrants, and lubricants.  
     
     
         11 . A tablet containing the composition of  claim 3 .  
     
     
         12 . A tablet containing the composition of  claim 5.