Box-Behnken效应面法优化多西他赛微乳注射液制备工艺

Optimization of the Preparation Technology of Docetaxel Microemulsion Injection by Box-Behnken Design and Response Surface Method

目的:优化微乳制备工艺,制备多西他赛微乳注射液。方法:采用高压均质法制备多西他赛微乳,以制备温度、均质压力和均质次数为考察对象,以粒径分布、多分散系数和包封率为评价指标,采用Box-Behnken效应面法优化多西他赛微乳的制备工艺;采用Mastersizer粒度仪测定微乳的粒径分布,考察多分散系数及Zeta电位,透射电镜考察其形态。结果:多西他赛微乳优化工艺为制备温度61℃,均质压力860×105Pa,均质次数7次;所得微乳的粒径为(221.6±13.4)nm,多分散系数为0.092±0.003,Zeta电位为-30.3mV,包封率为(93.4±2.1)%;透射电镜显示微乳粒径均一,呈球状分布。结论:多西他赛微乳制备工艺采用Box-Behnken效应面法优化是有效、可行的。

OBJECTIVE：To optimize the preparation technology of microemulsion,and to prepare Docetaxel microemulsion injection.METHODS：Docetaxel microemulsion was prepared using high pressure homogenization.The preparation technology of Docetaxel microemulsion was optimized by Box-Behnken design and response surface method with preparation temperature,homogenization pressure and homogenization times as factors using particle size distribution,polydispersity index and entrapment efficiency as index.The distribution of particle size,polydispersion index and Zeta potential were determined by Mastersizer particle analyzer;the morphology of Docetaxel microemulsion was observed under TEM.RESULTS：Optimized preparation technology was as follows：preparation temperature of 61 ℃,homogenization pressure of 860×10 5 Pa,homogenization times of 7.The microemulsions were characterized with particle size of（221.6±13.4）nm,polydispersion index of（0.092±0.003）,Zeta potential of-30.3 mV,encapsulation efficiency of（93.4 ± 2.1）%.The microemulsions were found to be homogeneous and spherical under TEM.CONCLUSIONS：It is effective and practical that Box-Behnken design and response method optimizes the preparation technology of Docetaxel microemulsion.