Pharmaceutical emulsions for retroviral protease inhibitors

Abstract

The present invention provides an emulsion formulation with high oral bioavailability containing lecithin as an emulsifier and solubilizing agent to achieve a high loading of the pyranone compound of formula I.

1 . A pharmaceutical composition comprising:  
     (a) a therapeutically effective amount of the compound of formula I  
     
       
         
         
             
             
         
       
     
     (b) an oil component selected from the group consisting of a 
 (i) mixture of diglyceride and monoglyceride in a ratio of from about 9:1 to about 1:9 by weight,  
 (ii) mixture of diglyceride and monoglyceride in a ratio of from about 8:2 (diglyceride:monoglyceride) by weight,  
 (iii) mixture of diglyceride and triglyceride in a ratio of from about 9:1 to about 1:9 by weight,  
 (iv) mixture of diglyceride and triglyceride in a ratio of from about 2:8 (diglyceride:triglyceride) by weight,  
 wherein the monoglyceride and diglyceride are mono- and di-unsaturated fatty acid esters of glycerol having 16 to 22 carbon atom chain length, wherein triglyceride is a saturated fatty acid ester of glycerol having 6 to 12 carbon atom chain length,  
 (c) an emulsifying agent consisting of lecithin, and  
 (d) a liquid phase comprising one or more pharmaceutically acceptable solvents,  
 and wherein said pharmaceutically acceptable composition does not contain either an amino acid, citric acid or a pharmaceutically acceptable salt of citric acid.  
 
   
   
       2 . A pharmaceutical composition of  claim 1  wherein the pyranone compound of formula I is in an amount of from about 1% to about 20% by weight of the total composition.  
   
   
       3 . A pharmaceutical composition of  claim 1  wherein the pyranone compound of formula I is in an amount of from about 2% to about 15% by weight of the total composition.  
   
   
       4 . A pharmaceutical composition of  claim 1  wherein the lecithin is yolk lecithin or soybean lecithin.  
   
   
       5 . A pharmaceutical composition of  claim 1  wherein the lecithin a synthetic nontoxic didecanoyl phosphatidycholine, dilauroyl phosphatidycholine, dimyristoyl phosphatidycholine, dipalmitoyl phosphatidycholine or a mixture thereof.  
   
   
       6 . A pharmaceutical composition of  claim 1  wherein the lecithin is in an amount of from about 0.5% to about 20% by weight of the total composition.  
   
   
       7 . A pharmaceutical composition of  claim 1  wherein the lecithin is in an amount of from about 1% to about 10% by weight of the total composition.  
   
   
       8 . A pharmaceutical composition of  claim 1  wherein the lecithin is in an amount of from about 2% to about 5% by weight of the total composition.  
   
   
       9 . A pharmaceutical composition of  claim 1  wherein the oil component is in an amount of from about 5% to about 40% by weight of the total composition.  
   
   
       10 . A pharmaceutical composition of  claim 1  wherein the oil component is in an amount of from about 10% to about 30% by weight of the total composition.  
   
   
       11 . A pharmaceutical composition of  claim 1  wherein the oil component is in an amount of from about 10% to about 20% by weight of total composition.  
   
   
       12 . A pharmaceutical composition of  claim 1  wherein the oil component is triglyceride.  
   
   
       13 . A pharmaceutical composition of  claim 1  wherein the oil component is a mixture of diglyceride and monoglyceride in a ratio of from about 9:1 to about 1:9 by weight.  
   
   
       14 . A pharmaceutical composition of  claim 1  wherein the oil component is a mixture of diglyceride and monoglyceride in a ratio of from about 8:2 (diglyceride:monoglyceride) by weight.  
   
   
       15 . A pharmaceutical composition of  claim 1  wherein the oil component is a mixture of diglyceride and triglyceride in a ratio of from about 9:1 to about 1:9 by weight.  
   
   
       16 . A pharmaceutical composition of  claim 1  wherein the oil component is a mixture of diglyceride and triglyceride in a ratio of from about 2:8 (diglyceride:triglyceride) by weight.  
   
   
       17 . A pharmaceutical composition of  claim 1  wherein the oil component is a mixture of monoglyceride, diglyceride and triglyceride in a ratio of from about 1 to about 8 parts of diglyceride per 10 parts of the mixture, about 1 to 5 parts of monoglyceride per 10 parts of the mixture, and about 1 to about 8 parts of triglyceride per 10 parts of the mixture.  
   
   
       18 . A pharmaceutical composition of  claim 1  wherein the pharmaceutically acceptable solvent is propylene glycol, polyethylene glycol, glycerol, triacetin, dimethyl isosorbide, glycofurol, propylene carbonate, ethanol, water, dimethyl acetamide or a mixture thereof.  
   
   
       19 . A pharmaceutical composition of  claim 1  wherein the pharmaceutically acceptable solvent is propylene glycol, water or a mixture thereof.  
   
   
       20 . A pharmaceutical composition of  claim 1  wherein the pharmaceutically acceptable solvent is water.  
   
   
       21 . A pharmaceutical composition of  claim 1  which is administered orally or parenterally.