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目的:通过优选工艺条件制备多西他赛人血白蛋白微球,并考察其体外缓释特性。方法:以人血白蛋白为药物载体,采用乳化-化学交联法制备多西他赛蛋白微球,HPLC测定多西他赛的浓度,通过L16(45)正交设计试验考察药质比、交联剂用量、交联时间、搅拌转速、酸碱度等因素对微球载药量和包封率的影响,利用极差分析和方差分析优选最佳工艺条件;扫描电镜观察微球形态;以累积释药百分率为指标考察微球体外释药特性。结果:最佳工艺条件为药质比为1∶7、交联剂用量为2.0mL、交联时间为1.5h、搅拌转速为300r·min-1、反应介质pH值为7.5;以优化工艺制备的微球在扫描电镜下可见为表面光滑的类球体,平均粒径为36.16μm,载药量为(11.74±0.26)%,包封率为(65.24±1.24)%,体外释药模式符合Higuchi方程Q=14.34t1/2+0.21(r=0.994 5),48h体外累积释药百分率为82.8%。结论:本实验通过优化工艺条件,制备完成载药量、包封率和缓释性均较为理想的多西他赛人血蛋白微球。
OBJECTIVE: To prepare docetaxel microspheres by optimizing the process conditions and investigate its in vitro sustained-release properties. Methods: The docetaxel microspheres were prepared by emulsification-chemical cross-linking method with human serum albumin as carrier. The concentration of docetaxel was determined by HPLC. The ratio of drug to drug was determined by orthogonal experiment L16 (45) The amount of crosslinking agent, crosslinking time, stirring speed, pH and other factors on the microspheres drug loading and encapsulation efficiency, the use of range analysis and variance analysis to optimize the optimal process conditions; scanning electron microscopy morphology of microspheres; to accumulate Drug release percentage as an index to investigate in vitro release characteristics of microspheres. Results: The optimum conditions were as follows: the ratio of drug to drug was 1: 7, the amount of crosslinking agent was 2.0mL, the crosslinking time was 1.5h, the stirring speed was 300r · min-1 and the pH of the reaction medium was 7.5. Of the microspheres can be seen as smooth spheroids under scanning electron microscopy. The average diameter of the microspheres is 36.16 μm, the drug loading is (11.74 ± 0.26)%, the entrapment efficiency is (65.24 ± 1.24)%. The in vitro drug release mode accords with Higuchi The equation Q = 14.34t1 / 2 + 0.21 (r = 0.994 5), the cumulative percentage of drug release in vitro was 82.8% in 48h. Conclusion: In this experiment, we optimized the process conditions to prepare docetaxel human hemoglobin microspheres with satisfactory drug loading, encapsulation efficiency and sustained release.