Pellets having a core coated with an antifungal and a polymer

Abstract

The present invention is concerned with pellets comprising a 710-1180 μm (16-25 mesh) sugar core, a coating film of a water-soluble polymer and an antifungal agent, and a seal coating layer wherein the residual concentration of dichloromethane is below 600 ppm; pharmaceutical dosage forms comprising said pellets and a method of preparing said pellets.

1 . A pellet comprising 
 a) a central, rounded or spherical core having a diameter from about 710 to about 1180 μm (16-25 mesh);    b) a coating film of a water-soluble polymer and an antifungal agent, and    c) a seal-coating polymer layer,    characterized in that the residual concentration of dichloromethane in said pellet is less than 600 ppm.    
     
     
         2 . A pellet according to  claim 1  comprising by weight based on the total weight of the pellet: 
 a) 35 to 60 percent core material;  
 b) 23 to 37 percent water-soluble polymer;  
 c) 15 to 25 percent antifungal agent; and  
 d) 2 to 4 percent seal-coating polymer.  
 
     
     
         3 . A pellet according to  claim 2  wherein the core material is a 710-850 μm (20-25 mesh) sugar core, the water-soluble polymer is hydroxypropyl methylcellulose and the antifungal agent is itraconazole.  
     
     
         4 . A pellet according to  claim 3  wherein the weight to weight ratio of antifungal agent:water-soluble polymer is about 1:1 to about 1:2.  
     
     
         5 . A pellet according to  claim 2  wherein the seal-coating polymer is polyethylene glycol.  
     
     
         6 . A pellet according to  claim 3  comprising approximately: 
 a) 40 to 43 percent sugar cores;  
 b) 30 to 35 percent hydroxypropyl methylcellulose 2910 5 mPa.s.  
 c) 20 to 25 percent itraconazole or saperconazole; and  
 d) 2 to 4 percent polyethylene glycol 20000.  
 
     
     
         7 . A pharmaceutical dosage form comprising an effective antifungal amount of pellets as claimed in any one of  claims 1  to  6 .  
     
     
         8 . A dosage form according to  claim 7  wherein the dosage form is a hard-gelatin capsule.  
     
     
         9 . A process for preparing pellets as claimed in any one of  claims 1  to  6  characterized by, 
 a) coating sugar cores by spraying onto them with a solution of an antifungal agent and a water-soluble polymer in an organic solvent consisting of methylene chloride and ethanol in a fluidized-bed granulator equipped with a Wurster (bottom spray) insert;  
 b) drying the resulting coated cores in vacuo by irradiating said cores with microwave or radiofrequency radiation; and  
 c) seal-coating the dried cores by spraying onto them with a solution of a seal-coating polymer in an organic solvent consisting of methylene chloride and ethanol in a fluidized-bed granulator equipped with a Wurster (bottom spray) insert.  
 
     
     
         10 . Drug-coated pellets obtainable by a process according to  claim 9.