Fenofibrate tablets

Abstract

The invention concerns a novel galenic formulation of fenofibrate for oral administration and its method of preparation. The invention is characterised in that it consists of a tablet obtained by compressing a mixture comprising: a) a granular material containing: 1 to 5% of a surfactant, micronized fenofibrate, at least a solid support selected among starch, cellulose or their derivatives, except C 12 disaccharides; said granular material being obtained by granulating the mixture using an aqueous polyvinylpyrrolidone solution; b) crosslinked polyvinylpyrrolidone; c) optionally flow or lubricating agents, the amount of fenofibrate being more than 50 wt. %, expressed relative to the tablet weight. The invention is useful for treating hypercholesterolemia and hypertriglyceridemia.

1 . Fenofibrate tablet, characterized in that it is obtained by compressing a mixture comprising: 
 a) granules containing: 
 1 to 5% of a surfactant;  
 micronized fenofibrate; and  
 at least one solid excipient selected from starch, cellulose and derivatives thereof, with the exception of C 12  disaccharides,  
 said granules being obtained by granulating the mixture with the aid of an aqueous solution of polyvinylpyrrolidone;  
   b) crosslinked polyvinylpyrrolidone; and    c) optionally flow aids or lubricants, the amount of fenofibrate being greater than 50% by weight, expressed relative to the weight of the tablet.    
     
     
         2 . Fenofibrate tablet according to  claim 1 , characterized in that the aforementioned surfactant used to obtain the granules is solid and takes the form of a comicronizate with the fenofibrate.  
     
     
         3 . Fenofibrate tablet according to  claim 1 , characterized in that the aforementioned surfactant used to obtain the granules is present in the granulating solution containing the polyvinylpyrrolidone.  
     
     
         4 . Fenofibrate tablet according to one of  claims 1  to  3 , characterized in that it contains between 50 and 250 mg of fenofibrate.  
     
     
         5 . Fenofibrate tablet according to one of  claims 1  to  4 , characterized in that the surfactant is sodium laurylsulfate.  
     
     
         6 . Fenofibrate tablet according to one of  claims 1  to  5 , characterized in that one of the aforementioned solid excipients is pregelatinized starch, which is present in an amount of 15 to 40% of the weight of the fenofibrate.  
     
     
         7 . Fenofibrate tablet according to one of  claims 1  to  5 , characterized in that one of the excipients is microcrystalline cellulose, which is present in an amount of 5 to 30% of the weight of the fenofibrate.  
     
     
         8 . Fenofibrate tablet according to one of  claims 1  to  7 , characterized in that the polyvinylpyrrolidone has an average molecular weight in the order of 25,000 to 100,000.  
     
     
         9 . Fenofibrate tablet according to one of  claims 1  to  8 , characterized in that the crosslinked polyvinylpyrrolidone is present in an amount of 6 to 18% and preferably of 10 to 14% of the weight of the fenofibrate.  
     
     
         10 . Fenofibrate tablet according to one of  claims 1  to  9 , characterized in that it has a coating consisting of a film of protective varnish, preferably based on a water-dispersible polymer.  
     
     
         11 . Process for the preparation of a pharmaceutical fenofibrate composition in the form of a tablet for oral administration, characterized in that it comprises: 
 the comicronization of an effective amount of fenofibrate and a solid surfactant, which is used in an amount of between 1 and 5% by weight, based on the weight of fenofibrate;    the mixing, in the form of powders, of the resulting product with at least one solid excipient selected from starch, cellulose and derivatives thereof, with the exception of C 12  disaccharides;    the granulation of the resulting mixture of powders with the aid of an aqueous solution of polyvinylpyrrolidone;    the mixing of the resulting granules with crosslinked polyvinylpyrrolidone and optionally flow aids or lubricants, it being specified that the amount of fenofibrate is greater than 50% by weight, expressed relative to the weight of the tablet;    the compression of the mixture produced; and    optionally the film-coating of the resulting tablet with a protective varnish, preferably based on a water-dispersible polymer.    
     
     
         12 . Process for the preparation of a pharmaceutical fenofibrate composition in the form of a tablet for oral administration, essentially characterized in that it comprises: 
 the mixing, in the form of powders, of micronized fenofibrate with at least one solid excipient selected from starch, cellulose and derivatives thereof, with the exception of C 12  disaccharides;    the granulation of the resulting mixture of powders with the aid of an aqueous solution of polyvinylpyrrolidone and a surfactant, said surfactant being in an amount of between 1 and 5% by weight, based on the weight of fenofibrate;    the mixing of the resulting granules with crosslinked polyvinylpyrrolidone and optionally flow aids or lubricants,    it being specified that the amount of fenofibrate is greater than 50% by weight, expressed relative to the weight of the tablet;    the compression of the mixture produced; and    optionally the film-coating of the resulting tablet with a protective varnish, preferably based on a water-dispersible polymer.    
     
     
         13 . Process according to  claim 11  or  12 , characterized in that the crosslinked polyvinylpyrrolidone is used in an amount of between 6 and 18% and preferably of between 10 and 14% by weight, based on the weight of fenofibrate.  
     
     
         14 . Process according to one of  claims 11  to  13 , characterized in that the aforementioned solid excipient(s) is (are) used in an amount of between 5 and 40% and preferably of between 10 and 35% by weight, based on the weight of fenofibrate.