Process of preparing microspheres for sustained release having improved dispersibility and syringeability

Abstract

Disclosed is a process of preparing sustained release microspheres, containing a biodegradable polymer as a carrier and a drug, using spray drying. The process comprises preparing a solution, suspension or emulsion containing a biodegradable polymer, a drug and a solvent; spray drying the solution, suspension or emulsion; and suspending spray-dried microspheres in an aqueous solution containing polyvinyl alcohol to remove the residual solvent and increase the hydrophilicity of the microsphere surface. The process enables the preparation of microspheres having high drug encapsulation efficiency, almost not having a toxicity problem due to the residual solvent, and having good syringeability. The microspheres prepared according to the present invention release an effective concentration of a drug in a sustained manner for a predetermined period when administered to the body, and are thus useful in the treatment of diseases.

1 . A process of preparing a sustained release microsphere, comprising:
 spraying a solution, suspension or emulsion containing a biodegradable polymer, a drug and a solvent into a dry chamber and drying it using dry air to remove the solvent; and   dispersing a spray-dried microsphere in an aqueous solution containing polyvinyl alcohol to remove a residual solvent and improve dispersibility of the microsphere.   
     
     
         2 . The process of preparing the sustained release microsphere according to  claim 1 , wherein the biodegradable polymer is one or more selected from the group consisting of polylactide, polyglycolide, poly(lactide-co-glycolide), polyorthoester, polyanhydride, polyhydroxybutyric acid, polycaprolactone, polyalkylcarbonate, and derivatives thereof. 
     
     
         3 . The process of preparing the sustained release microsphere according to  claim 1 , wherein the drug is selected from among a peptide and a protein. 
     
     
         4 . The process of preparing the sustained release microsphere according to  claim 3 , wherein the drug is, selected from among luteinizing hormone releasing hormone (LHRH) derivatives, somatostatin derivatives, and salts thereof. 
     
     
         5 . The process of preparing the sustained release microsphere according to  claim 4 , wherein the drug is selected from among leuprolelin, goserelin, triptorelin, octreotide, and salts thereof. 
     
     
         6 . The process of preparing the sustained release microsphere according to  claim 1 , wherein in the dispersing in the aqueous solution containing polyvinyl alcohol, polyvinyl alcohol is coated on the sustained release microsphere in an amount from 0.02% to 1.0% by weight. 
     
     
         7 . The process of preparing the sustained release microsphere according to  claim 1 , wherein in the dispersing in the aqueous solution containing polyvinyl alcohol, the residual solvent in the sustained release microsphere is additionally removed by more than 20%. 
     
     
         8 . A drug-loaded sustained release microsphere, which is prepared by atomizing a solution, suspension or emulsion containing a biodegradable polymer, a drug and a solvent into droplets, drying the atomized droplets to remove the solvent and obtain a dried microsphere, and dispersing the dried microsphere in an aqueous solution containing polyvinyl alcohol to coat polyvinyl alcohol on the microsphere in an amount from 0.02% to 1.0% by weight. 
     
     
         9 . The drug-loaded sustained release microsphere according to  claim 8 , wherein the drug is selected from among a peptide and a protein. 
     
     
         10 . The drug-loaded sustained release microsphere according to  claim 9 , wherein the drug is selected from among luteinizing hormone releasing hormone (LHRH) derivatives, somatostatin derivatives, and salts thereof. 
     
     
         11 . The drug-loaded sustained release microsphere according to  claim 10 , wherein the drug is selected from among leuprolelin, goserelin, triptorelin, octreotide, and salts thereof.