Antifungal composition with enhanced bioavailability

Abstract

A liquid suspension comprising an antifungally effective amount of the micronized compound represented by the chemical structural formula I: at least one thickening agent, a non-ionic surfactant, and a pharmaceutically acceptable liquid carrier is disclosed.

We claim:  
     
         1 . A liquid suspension comprising an antifungally effective amount of the micronized compound represented by the chemical structural formula I comprising:  
       
         
           
           
               
               
           
         
       
       at least one thickening agent, at least one non-ionic surfactant, and a pharmaceutically acceptable liquid carrier.  
     
     
         2 . The liquid suspension of  claim 1 , wherein the at least one non-ionic surfactant is a block copolymer of ethylene oxide and propylene oxide, glycol or glyceryl esters of saturated or unsaturated C 8 to C 20  acids, polyoxyethylene esters of saturated or unsaturated C 8 to C 20  acids, polyoxyethylene ethers of saturated or unsaturated C 8 to C 20  acids, polyvinylalcohols or sorbitan esters of saturated or unsaturated C 10  to C 20  acids.  
     
     
         3 . The liquid suspension of  claim 1 , wherein the at least one non-ionic surfactant is a polyoxyethylene derivative of a sorbitan ester of a saturated or unsaturated C 10 to C 20  acid.  
     
     
         4 . The liquid suspension of  claim 1 , wherein the at least one thickening agent is selected from xanthan gum, liquid sugars, starches, celluloses and mixtures thereof.  
     
     
         5 . The liquid suspension of  claim 1 , wherein a combination of xanthan gum and a liquid sugar are used as the at least one thickening agent.  
     
     
         6 . The liquid suspension of  claim 1 , wherein the micronized compound of formula I has a mean particle size of about 1200 nm to about 1600 nm.  
     
     
         7 . A liquid suspension comprising: 
 (a) an antifungally effective amount of the micronized compound represented by the chemical structural formula I:                          (b) an effective amount of at least one thickening agent;    (c) an amount of a buffer system effective to maintain the pH of the system in the range of about 4.0 to about 6.0;    (d) an effective amount of at least one non-ionic surfactant; and    (e) a pharmaceutically acceptable liquid carrier.    
     
     
         8 . The liquid suspension of  claim 7 , wherein the at least one non-ionic surfactant is a polyoxyethylene derivative of a sorbitan ester of a saturated or unsaturated C 10 to C 20  acid.  
     
     
         9 . The liquid suspension of  claim 7 , wherein the sorbitan ester is a fatty acid ester of sorbitan selected from sorbitan monolaurate, sorbitan monooleate, sorbitan sesquioleate, sorbitan trioleate, sorbitan monopalmitate, sorbitan monostearate and sorbitan tristearate, or mixtures thereof.  
     
     
         10 . The liquid suspension of  claim 7 , wherein the at least one thickening agent is selected from gums, liquid sugars, starches, cellulose and mixtures thereof.  
     
     
         11 . The liquid suspension of  claim 7 , wherein a combination of a xanthan gum and a liquid sugar is used as the at least one thickening agent.  
     
     
         12 . The liquid suspension of  claim 7 , wherein a combination of a xanthan gum and a liquid glucose is used as the thickening agent.  
     
     
         13 . The liquid suspension of  claim 7 , wherein the buffer system comprises sodium citrate and citric acid.  
     
     
         14 . The liquid suspension of  claim 7 , wherein the pharmaceutically acceptable liquid carrier is a combination of purified water, glucose and glycerin.  
     
     
         15 . The liquid suspension of  claim 7 , wherein the micronized compound of formula I has a mean particle size of about 1200 nm to about 1600 nm.  
     
     
         16 . A liquid suspension comprising: 
 (a) an antifungally effective amount of the micronized compound comprising chemical structural formula I:                           wherein the micronized compound of formula I has a mean particle size in the range of about 1200 nm to about 1600 nm,    (b) an effective amount of a polyoxyethylene derivative of sorbitan esters of saturated or unsaturated C 12  to C 18  acids;    (c) an effective amount of a buffer system sufficient to maintain a pH in the range of about 4.0 to about 6.0;    (d) an effective amount of a combination of two thickening agents, wherein one is a liquid sugar; and    (e) a pharmaceutically acceptable liquid carrier.    
     
     
         17 . A method of treating and/or preventing a fungal infection in a patient comprising administering to a patient in need of such treating and/or preventing an antifungally effective amount of micronized particles of of the compound of formula I in the form of an oral suspension I:  
       
         
           
           
               
               
           
         
       
     
     
         18 . A suspension comprising an antifungally effective amount of the micron ized particles of the compound comprising chemical structural formula I:  
       
         
           
           
               
               
           
         
       
       at least one thickening agent and a non-ionic surfactant in a pharmaceutically acceptable liquid carrier.  
     
     
         19 . A composition of matter comprising micronized particles of the compound represented by structural formula I  
       
         
           
           
               
               
           
         
       
       and at least one non-ionic surfactant.  
     
     
         20 . A composition of matter comprising micronized particles of the compound represented by chemical structural formula I:  
       
         
           
           
               
               
           
         
       
       in suspension.