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,    wherein the residual concentration of dichloromethane in said pellet is less than 600 ppm.    
     
     
         2 . A pellet according to  claim 1  comprising approximately, 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 to 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; and    d) 2 to 4 percent polyethylene glycol 20000.    
     
     
         7 . A pharmaceutical dosage form comprising an effective antifungal amount of pellets as claimed in  claim 1 .  
     
     
         8 . A dosage form according to  claim 7  wherein the dosage form is a hard-gelatin capsule.  
     
     
         9 - 10 . (canceled)  
     
     
         11 . The pellet of  claim 1  wherein the coating film is an irradiated coating film.  
     
     
         12 . The pellet of  claim 11 , wherein the radiation is microwave or radiofrequency radiation.  
     
     
         13 . A method of treating a patient suffering from a fungal infection comprising administering a therapeutically effective amount of pellets as claimed in  claim 1 .  
     
     
         14 . Pellets made by a process comprising: 
 coating sugar cores having a diameter from about 710 to about 1180 μm (16-25 mesh) by spraying them with a solution of an antifungal agent and a water-soluble polymer in an organic solvent comprising methylene chloride and an alcohol;    drying the resulting coated cores in vacuo by irradiating said cores with microwave or radiofrequency radiation; and    seal-coating the dried cores by spraying them with a solution of a seal-coating polymer in an organic solvent comprising methylene chloride and an alcohol,    wherein said pellets have a residual concentration of dichloromethane of less than 600 ppm.    
     
     
         15 . The pellets of  claim 14  wherein the antifungal agent is selected from itraconazole or saperconazole.  
     
     
         16 . The pellets of  claim 15  wherein the antifungal agent is itraconazole.  
     
     
         17 . The pellets of  claim 14  wherein the water-soluble polymer is hydroxypropyl methylcellulose and the antifungal agent is itraconazole.  
     
     
         18 . The pellets of  claim 14  wherein the seal-coating polymer is polyethylene glycol.  
     
     
         19 . The pellets of  claim 14 , wherein the alcohol is ethanol.