Sustained-release pharmaceutical formulations containing mizolastine

Abstract

A sustained-release pharmaceutical formulation containing mizolastine, a core formed of a sustained-release table containing mizolastine combined with a fatty matrix and an organic acid, the tablet being coated.

1 - 7 . (canceled)  
     
     
         8 . A coated sustained release tablet, consisting essentially of from 0.5% to 12% by weight of mizolastine, a fatty matrix, an organic acid and a coating.  
     
     
         9 . A coated sustained release tablet according to  claim 8 , which has a dissolution profile which is pH independent.  
     
     
         10 . A coated sustained release tablet, consisting essentially of mizolastine, a fatty matrix, an organic acid, and a coating, the coated tablet having a dissolution profile which is pH independent, the organic acid being a member selected from the group consisting of maleic, tartaric, malic, fumaric, lactic, citric, adipic and succinic acid in the form of a racemate or an isomer.  
     
     
         11 . A pharmaceutical dosage form which comprises a coated tablet having a sustained-release core, said core comprising a combination of: 
 a) mizolastine as active principle;    b) a fatty matrix; and    c) an organic acid;    wherein the coated tablet has a dissolution profile wherein about 50% of the mizolastine is dissolved in 1 hour, and 100% of the mizolastine is dissolved in 3 to 5 hours.    
     
     
         12 . A sustained-release pharmaceutical dosage form according to  claim 11  wherein the weight ratio of the mizolastine to the organic acid is between 0.3 and 1.  
     
     
         13 . A sustained-release pharmaceutical dosage form according to  claim 11  wherein the fatty matrix is a member selected from the group consisting of hydrogenated castor oil, a hydrogenated lecithin, a long-chain fatty acid and a triglyceride esterified with one, two or three medium-chain fatty acids.  
     
     
         14 . A sustained-release pharmaceutical dosage form according to  claim 11  wherein the organic acid is a member selected from the group consisting of maleic, tartaric, malic, fumaric, lactic, citric, adipic and succinic acid in the form of a racemate or an isomer.  
     
     
         15 . A sustained-release pharmaceutical dosage form according to  claim 11  wherein the organic acid is L-tartaric acid.  
     
     
         16 . A sustained-release pharmaceutical dosage form according to  claim 15  wherein the ratio between the mizolastine and the L-tartaric acid is 0.5.  
     
     
         17 . A sustained-release pharmaceutical dosage form according to  claim 9  which contains from 1 to 25 mg of mizolastine.  
     
     
         18 . A coated sustained-release tablet having: 
 a) a core comprising mizolastine, a fatty matrix and an organic acid;    b) a dissolution profile which is pH independent;    c) an in vivo mizolastine release which prevents any plasma peak; and    d) a mizolastine bioavailability which is not decreased relative to that of an immediate release formulation;    wherein the mizolastine comprises from 0.5% to 12% by weight of the tablet.    
     
     
         19 . A sustained-release tablet of  claim 18  wherein the dissolution profile is one in which about 30 to 70% of the mizolastine is dissolved in 1 hour and 100% of the mizolastine is dissolved in 3 to 5 hours.  
     
     
         20 . A sustained-release tablet of  claim 18  wherein the weight ratio between the mizolastine and the organic acid is between 0.3 and 1.  
     
     
         21 . A sustained-release tablet of  claim 18  wherein the fatty matrix is a member selected from the group consisting of hydrogenated castor oil, a hydrogenated lecithin, a long-chain fatty acid and a triglyceride esterified with one, two or three medium-chain fatty acids.  
     
     
         22 . A sustained-release tablet of  claim 18  wherein the organic acid is a member selected from the group consisting of maleic, tartaric, malic, fumaric, lactic, citric, adipic and succinic acid in the form of a racemate or an isomer.  
     
     
         23 . A sustained-release tablet of  claim 18  wherein the organic acid is L-tartaric acid.  
     
     
         24 . A sustained-release tablet of  claim 23  wherein the ratio between the mizolastine and the L-tartaric acid is 0.5.  
     
     
         25 . A sustained-release tablet of  claim 18  wherein the core contains from 1 to 25 mg of mizolastine.  
     
     
         26 . A sustained-release tablet of  claim 18  wherein the organic acid has a pK of 2 or more.  
     
     
         27 . A coated sustained-release tablet comprising from 1 to 25 mg of mizolastine, a fatty matrix and L-tartaric acid, and the weight ratio of the mizolastine and the L-tartaric acid is between 0.3 and 1.  
     
     
         28 . A coated sustained-release tablet of  claim 27 , wherein the ratio between the mizolastine and the L-tartaric acid is 0.5.  
     
     
         29 . A coated sustained-release tablet of  claim 28 , wherein the fatty matrix is hydrogenated castor oil.  
     
     
         30 . A coated sustained-release tablet of  claim 29 , wherein the tablet has a dissolution profile which is independent of pH and is one in which about 50% of the mizolastine is dissolved in 1 hour and 100% of the mizolastine is dissolved in 3 to 5 hours.