Method for producing solid-lipid composite drug particles

Abstract

A method of producing solid composite lipid/drug nanoparticles that includes the steps of: (1) dissolving a lipid and a drug in a suitable organic solvent to form a solution; (2) emulsifying the solution in a liquid to form an emulsion having a discontinuous phase of micelles comprising the organic solvent, the drug and the lipid, and a continuous phase comprising the liquid; and (3) contacting the emulsion with a supercritical fluid under conditions suitable to keep the supercritical fluid in a supercritical state, whereby the supercritical fluid extracts the organic solvent from the micelles, causing them to precipitate as organic-solvent free solid composite lipid/drug nanoparticles suspended or dispersed in the liquid.

1 . A method of producing a suspension or dispersion of solid composite lipid/drug nanoparticles in a liquid comprising: 
 dissolving a lipid and a drug in a suitable organic solvent to form a solution;    emulsifying the solution in the liquid to form an emulsion having a discontinuous phase of micelles comprising the organic solvent, the drug and the lipid, and a continuous phase comprising the liquid; and    contacting the emulsion with a supercritical fluid under conditions suitable to keep the supercritical fluid in a supercritical state, whereby the supercritical fluid extracts the organic solvent from the micelles, causing the micelles to precipitate into the liquid and thus form the suspension or dispersion of solid composite lipid/drug nanoparticles in the liquid.    
     
     
         2 . The method according to  claim 1  wherein the liquid is water.  
     
     
         3 . The method according to  claim 2  wherein a surfactant is dissolved in the water before the solution is emulsified in the water.  
     
     
         4 . The method according to  claim 3  wherein a co-surfactant is dissolved in the solution before the solution is emulsified in the water.  
     
     
         5 . The method according to  claim 2  wherein the supercritical fluid is supercritical carbon dioxide.  
     
     
         6 . The method according to  claim 5  wherein the organic solvent is chloroform.  
     
     
         7 . The method according to  claim 1  wherein the weigh ratio of the drug to the lipid in the solution is from about 0.1:99.9 to about 50:50.  
     
     
         8 . The method according to  claim 1  wherein the average particle size of the solid composite lipid/drug nanoparticles is from about 5 nm to about 1000 nm.  
     
     
         9 . The method according to  claim 1  wherein the emulsion and the supercritical fluid contact each other as contra-current flows in an extraction chamber.