Pharmaceutical composition for oral use comprising an active principle liable to undergo a large first intestinal passage effect

Abstract

A pharmaceutical composition for oral use is disclosed. It includes, as active principle, a drug liable to undergo a strong first intestinal passage effect and a carrier which is self-micro-emulsifying on contact with an aqueous phase. The carrier includes: a therapeutically effective amount of the active principle; a lipophilic phase, which is a mixture of glycerol mono-, di- and triesters and of PEG mono- and diesters with at least one fatty acid chosen from the group comprising C8-C18 fatty acids; a surfactant phase which is a mixture of glycerol mono-, di- and triesters and of PEG mono- and diesters with caprylic acid (C8) and capric acid (C10); a co-surfactant phase which is an ester of a polyvalent alcohol with at least one fatty acid chosen from the group comprising caprylic esters of propylene glycol, lauric esters of propylene glycol and oleic esters of polyglycerol. A method of decreasing the effect of intestinal metabolism on a drug using the composition is also disclosed.

1 . Use of an oral pharmaceutical composition to reduce the intestinal passage effect on the active principle contained in, the said composition being in the form of a system which is self-microemulsifying on contact with an aqueous phase, comprising: 
 a therapeutically effective amount of the said active principle;    a lipophilic phase comprising a mixture of glycerol mono-, di- and triesters and of PEG mono- and diesters with at least one fatty acid chosen from the group comprising C 8 -C 18  fatty acids;    a surfactant phase comprising a mixture of glycerol mono-, di- and triesters and of PEG mono- and diesters with caprylic acid (C 8 ) and capric acid (C 10 );    a co-surfactant phase comprising at least one ester of a polyvalent alcohol with at least one fatty acid chosen from the group comprising caprylic esters of propylene glycol, lauric esters of propylene glycol and oleic esters of polyglycerol,    the ratio TA/CoTA being between 0.2 and 6.    
     
     
         2 . Use according to  claim 1 , characterized in that the lipophilic phase comprises a mixture of glycerol mono-, di- and triesters and of PEG mono- and diesters with the combination of saturated C 8 -C 18  fatty acids, the said mixture having an HLB value equal to 14 and representing between 50 and 95% by weight of the composition.  
     
     
         3 . Use according to  claim 1 , characterized in that the surfactant phase represents between 1% and 30% by weight of the mixture.  
     
     
         4 . Use according to  claim 1 , characterized in that the co-surfactant phase is a monoester of propylene glycol chosen from the group comprising propylene glycol monocaprylate and propylene glycol monolaurate.  
     
     
         5 . Use according to  claim 4 , characterized in that, when the surfactant phase contains propylene glycol monocaprylate, it represents between 3% and 32% by weight of the composition.  
     
     
         6 . Use according to  claim 4 , characterized in that, when the co-surfactant phase contains propylene glycol monolaurate, it represents between 1% and 8% by weight of the composition.  
     
     
         7 . Use according to  claim 1 , characterized in that the active principle belongs to the statin family.  
     
     
         8 . Use according to  claim 7 , characterized in that the statin is simvastatin.  
     
     
         9 . Use according to  claim 8 , characterized in that the simvastatin represents between 0.1% and 6% by weight of the composition and advantageously 4% by weight.  
     
     
         10 . Use according to  claim 1 , characterized in that the composition comprises by weight: 
 between 0.1% and 6% of simvastatin,    between 52% and 70% of Gélucire® 44/14,    between 5% and 30% of Labrasol®,    between 15% and 30% of propylene glycol monocaprylate.    
     
     
         11 . Use according to  claim 10 , characterized in that the propylene glycol monocaprylate consists of Capryol® PGMC representing between 15% and 25% by weight of the composition.  
     
     
         12 . Use according to  claim 10 , characterized in that the propylene glycol monocaprylate consists of Capryol® 90 representing between 20% and 30% by weight of the composition.  
     
     
         13 . Use according to  claim 1 , characterized in that the composition comprises by weight: 
 between 0.1% and 6% of simvastatin,    between 52% and 70% of Gélucire® 44/14,    between 5% and 30% of Labrasol®,    between 1% and 8% of Lauroglycol® 90.    
     
     
         14 . Pharmaceutical composition for oral use that is in the form of a system which is self-microemulsifying on contact with an aqueous phase, comprising: 
 a therapeutically effective amount of the said active principle;    a lipophilic phase comprising a mixture of glycerol mono-, di- and triesters and of PEG mono- and diesters with at least one fatty acid chosen from the group comprising C 8 -C 18  fatty acids;    a surfactant phase comprising a mixture of glycerol mono-, di- and triesters and of PEG mono- and diesters with caprylic acid (C 8 ) and capric acid (C 10 );    a co-surfactant phase comprising at least one ester of a polyvalent alcohol with at least one fatty acid;    the ratio TA/CoTA being between 0.2 and 6,    characterized in that the ester of a polyvalent alcohol with at least one fatty acid in the co-surfactant phase is chosen from the group comprising caprylic esters of propylene glycol.    
     
     
         15 . Composition according to  claim 14 , characterized in that the lipophilic phase comprises a mixture of glycerol mono-, di- and triesters and of PEG mono- and diesters with the combination of saturated C 8 -C 18  fatty acids, the said mixture having an HLB value equal to 14 and representing between 50 and 95% by weight of the composition.  
     
     
         16 . Composition according to  claim 14 , characterized in that the surfactant phase represents between 1% and 30% by weight of the mixture.  
     
     
         17 . Composition according to  claim 14 , characterized in that the co-surfactant phase represents between 3% and 32% by weight of the mixture.  
     
     
         18 . Composition according to  claim 14 , characterized in that the active principle belongs to the statin family.  
     
     
         19 . Composition according to  claim 18 , characterized in that the statin is simvastatin.  
     
     
         20 . Composition according to  claim 19 , characterized in that the simvastatin represents between 0.1% and 6% by weight of the composition and advantageously 4% by weight.  
     
     
         21 . Composition according to  claim 14 , characterized in that it comprises by weight: 
 between 0.1% and 6% of simvastatin,    between 52% and 70% of Gélucire® 44/14,    between 5% and 30% of Labrasol®,    between 15% and 30% of propylene glycol monocaprylate.    
     
     
         22 . Composition according to  claim 21 , characterized in that the propylene glycol monocaprylate consists of Capryol® PGMC representing between 15% and 25% by weight of the composition.  
     
     
         23 . Composition according to  claim 21 , characterized in that the propylene glycol monocaprylate consists of Capryol® 90 representing between 20% and 30% by weight of the composition.  
     
     
         24 . Composition according to  claim 21 , characterized in that the ratio TA/CoTA is equal to 0,5.