Study Of Risperidone Substained-release Microspheres For Injection

Risperidone is a new antipsychotic drug for the treatment of acute and chronic schizophrenia.It has a good effect on positive and negative symptoms.Poly(lactic-co-glycolic acid)(PLGA)is a kind of organic polymer with high molecular weight.As a degradable,non-toxic,and biodegradable copolymer,PLGA has excellent encystation and film-forming properties.Therefore,it has been approved by FDA as a pharmaceutical excipient and included into United States Pharmacopeia(USP)and Chinese Pharmacopoeia(Ch P).In this paper,injectable PLGA microspheres were fabricated by the emulsion-solvent evaporation and extraction method with risperidone as a model drug,PLGA as carrier material,benzyl alcohol and ethyl acetate as solvents.In most traditional processes,dichloromethane(DCM)was used as the solvent.Whereas,in this study,the non-toxic solvents of type III was applied to replace DCM in the preparation of PLGA microspheres.Such solvent system could not only solve the conglutination of microspheres,but also effectively reduce environmental pollution and the potential toxicity of the final products.Up to now,there was no domestic report about the preparation of risperidone-loaded microspheres using benzyl alcohol and ethyl acetate as solvents.In this paper,characterization methods of final microspheres,i.e.morphology,particle size,molecular weight,drug loading,encapsulation efficiency,and solvent residue,were established.Besides,the release profiles of risperidone from risperidone-loaded microspheres was also studied.The final risperidone-loaded microspheres were white particulates with a particle size of 84.6±2.1μm,molecular weight of 85±5 k D,drug loading of 37.8±0.4 %,and a encapsulation efficiency of 90±1 %.The residue of ethanol,ethyl acetate and benzyl alcohol were all within the limits required by Ch P.In release studies,the risperidone-loaded microspheres displayed an “S-shaped” curve.Moreover,the release profile with a small burst release amount lasted for 2 to 3 weeks.The in vitro release profile had a 53 % similarity with the commercial formulation conducted by Janssen.