Study Of Risperidone Substained-release Microspheres For Injection

Risperidone is a new antipsychotic drug for the treatment of acute and chronic schizophrenia.Poly(lactic-co-glycolic acid)(PLGA)is a kind of organic polymer with high molecular weight which is degradable,non-toxic,with good biocompatibility,encystation and film-forming properties.In this study,risperidone /PLGA sustained-release microspheres was prepared by the emulsified solvent evaporation /extraction method.A new mixed solvent system of three kinds of solvent ethyl acetate and benzyl alcohol is used to effectively reduce environmental pollution and reduce the potential toxicity of the final product.The emulsion was emulsified with a static mixer,and the microspheres were relatively uniform,and the amplification effect was small.It was beneficial to the quality control of the microspheres and the later amplification test.The steps of washing are optimized,and the residual solvents in the microspheres can be removed effectively.This paper has established the methods of detecting microspheres’ morphology,particle size,molecular weight,drug loading,encapsulation efficiency,solvent residue and some other quality characteristics.Besides,we study its in vitro release characteristics.The self-prepared Risperidone Microspheres are white powder;average particle size 100μm;molecular weight about 100 k D;drug loading 38%;encapsulation efficiency about90%.The amount of residue of ethanol,ethyl acetate and benzyl alcohol are all within the limits required by Ch P.It shows S-shaped curve in vitro release at 37 ℃ with small burst and a lone extended release time about 2 to 3 weeks.We find the self-prepared Risperidone Microspheres have fine characteristics in vitro release which get similarity with the commercial formulation Risperdal Consta conducted by Janssen.The subject is to realize the industrialization of risperidone microspheres as the main line,and the experiment is to prepare the step by step amplification process.First of all,the continuous and stable 4.5 g scale products are obtained through the optimization of the prescription and process.Then it was verified by 45 g scale amplification,product quality analysis and in vitro release detection.After optimizing the emulsification and drying process,increasing yield and improving the release characteristics,it was further enlarged to the pilot scale of 125 g industry.Combined with the surface morphology,drug loading and in vitro release characteristics of microspheres,the production process of industrial microspheres is further optimized through the quality control and process parameters adjustment in the process of microsphere preparation,and finally the industrial scale enlargement is achieved.