Method of Producing Microparticles

Abstract

A method of producing microparticles having a median diameter up to 100 μm and the microparticles so produced are described. The method includes the steps of providing a solvent having a bioactive dispersed or dissolved therein and a vehicle dissolved therein, carrying out an emulsification in a non-solvent phase to produce an emulsion containing the bioactive and the vehicle in a solvent phase, and evaporating the solvent to leave the microparticles, wherein a mixture of at least two surfactants is employed to stabilize the emulsion and wherein the mixture has a hydrophilic-lipophilic balance (HLB) of up to 8.

We claim: 
     
         1 . A method of producing microparticles comprising a bioactive and a vehicle, which method comprises:
 providing a solvent having a bioactive dispersed or dissolved therein and a vehicle dissolved therein,   carrying out an emulsification in a non-solvent phase to produce an emulsion comprising the bioactive and the vehicle in a solvent phase, and   evaporating the solvent to leave said microparticles, wherein a mixture of at least two surfactants is employed to stabilize the emulsion and wherein the mixture has a hydrophilic-lipophilic balance (HLB) of up to 8, and wherein the method yields microparticles having a median diameter of up to 100 μm.   
     
     
         2 . A method as claimed in  claim 1 , wherein said HLB is from 2 to 7. 
     
     
         3 . A method as claimed in  claim 1 , wherein said HLB is from 3 to 5. 
     
     
         4 . A method as claimed in  claim 1 , wherein said HLB is from 3 to 4. 
     
     
         5 . A method as claimed in  claim 1 , wherein said mixture comprises sorbitan monoleate and sorbitan dioleate. 
     
     
         6 . A method as claimed in  claim 1 , wherein said mixture is an equimolar mixture of two surfactants. 
     
     
         7 . A method as claimed in  claim 1 , wherein the vehicle is a polymer which enables pH-dependent and/or pH-independent release of the bioactive in the gastrointestinal tract. 
     
     
         8 . A method as claimed in  claim 1 , wherein the vehicle is a polymer which enables pH-dependent release of the bioactive in the gastrointestinal tract. 
     
     
         9 . A method as claimed in  claim 1 , wherein the vehicle is an acrylic-based polymer, a cellulose-based polymer, or a polyvinyl-based polymer. 
     
     
         10 . A method as claimed in  claim 9 , wherein the vehicle is a methacrylate polymer. 
     
     
         11 . A method as claimed in  claim 1 , wherein the vehicle comprises Eudragit® L100, Eudragit® L100-55, Eudragit® S100, Eudragit® P4135, Eudragit® RS100, or ethylcellulose. 
     
     
         12 . A method as claimed in  claim 1 , wherein the vehicle is not Eudragit® RS alone. 
     
     
         13 . A method as claimed in  claim 1 , wherein the bioactive is prednisolone, bendrofluazide, or budesonide. 
     
     
         14 . A method as claimed in  claim 1 , wherein the solvent is ethanol or a mixture of acetone and ethanol or methanol. 
     
     
         15 . A method as claimed in  claim 1 , wherein the surfactants in said mixture are both added to the solvent phase, both added to the non-solvent phase, or wherein one is added to each phase. 
     
     
         16 . A method as claimed in  claim 1 , wherein the non-solvent phase is liquid paraffin. 
     
     
         17 . A method as claimed in any preceding claim, wherein the emulsification is carried out at a temperature from 10 to 30° C. 
     
     
         18 . A composition of microparticles obtainable by means of a method comprising:
 providing a solvent having a bioactive dispersed or dissolved therein and a vehicle dissolved therein,   carrying out an emulsification in a non-solvent phase to produce an emulsion comprising the bioactive and the vehicle in a solvent phase, and   evaporating the solvent to leave said microparticles, wherein a mixture of at least two surfactants is employed to stabilized the emulsion and wherein the mixture has a hydrophilic-lipophilic balance (HLB) of up to 8, and wherein the method yields microparticles having a median diameter of up to 100 μm.   
     
     
         19 . A method of medical treatment comprising administering to a patient an effective amount of microparticles as claimed in  claim 18 .