目的:制备阿立哌唑缓释微球,使用星点设计-效应面法优化工艺,并对其体内血药浓度进行分析。方法:采用乳化溶剂挥发法制备阿立哌唑微球;以油相二氯甲烷体积、水相聚乙烯醇质量分数及乳化转速为自变量,以微球的平均粒径、跨距、载药量、包封率、产率及突释量为因变量,对制备工艺进行优化,并对优化后的工艺进行验证。采用HPLC法测定家兔血浆中药物浓度。结果:最佳工艺为二氯甲烷体积1.62mL,聚乙烯醇质量分数1.91%,乳化转速2 161 r.min-1;按优化工艺制备的微球外观圆整、流动性好;平均粒径为41.54μm,跨距为1.01,载药量为18.82%,包封率为75.39%,产率为85.17%,突释为1.68%。自制微球制剂在家兔体内d 1有少量的突释,d 5～d 20维持较稳定的血药浓度,缓慢释放,之后浓度开始下降。结论:所优化的制备工艺重现性好,简单易行;星点设计-效应面法优化微球制备工艺预测性良好,所制备的微球具有较好的体外缓释特性;阿立哌唑缓释微球在家兔体内缓慢释放,该释药行为达到了预期的目的。 OBJECTIVE: To prepare aripiprazole sustained-release microspheres and optimize the technology by using the method of star-point design-response surface methodology, and analyze its plasma concentration in vivo. Methods: The aripiprazole microspheres were prepared by the method of emulsion solvent evaporation. Taking the volumes of methylene chloride in the oil phase, the mass fraction of polyvinyl alcohol in the aqueous phase and the emulsifying speed as the independent variables, the average particle diameter, , Entrapment efficiency, yield and burst release as dependent variables, the preparation process is optimized, and the optimized process is verified. Determination of drug concentration in rabbit plasma by HPLC method. Results: The optimum conditions were as follows: volume of dichloromethane 1.62mL, mass fraction of polyvinyl alcohol 1.91%, emulsifying speed 2161 r.min-1. The microspheres prepared by the optimization process showed good appearance and good fluidity. The average particle size was 41.54μm, the span was 1.01, the drug loading was 18.82%, the encapsulation efficiency was 75.39%, the yield was 85.17% and the burst was 1.68%. The homemade microspheres had a small amount of burst release on d 1 in rabbits. The steady-state plasma concentration was maintained at d 5 ~d 20 and slowly released. Then the concentration began to drop. Conclusion: The optimized preparation process has good reproducibility and is simple and easy to implement. The design of star-point-response surface-optimized microspheres has good predictability, the prepared microspheres have better in vitro sustained-release properties and aripiprazole Slow release of sustained release microspheres in rabbits, the release of the drug to achieve the desired purpose.