岩白菜素Soluplus/TPGS混合胶束的制备、表征及体外释药研究

Preparation,characterization and drug release in vitro of bergenin Soluplus/TPGS mixed micelles

目的:制备岩白菜素Soluplus/TPGS混合胶束(bergenin mixed micelles,Ber-MM),评价其体外释药行为。方法:薄膜水化法制备Ber-MM。选择包封率和载药量为指标,Box-Behnken设计-效应面法优化Ber-MM处方工艺,并制备冻干粉。X-射线粉末衍射分析Ber-MM晶型,透射电镜观察Ber-MM微观形态,透析法考察Ber-MM在pH 1.2、pH 4.5和pH 6.8介质中的释药行为,并对释药模型进行拟合。结果:Ber-MM最佳处方为:Soluplus/TPGS比例为8.3∶1、载体与药物比例为8.8∶1、水化体积为20.5 mL。包封率、载药量、粒径及Zeta电位分别为(93.56±1.34)%、(9.50±0.18)%、(71.19±4.08)nm和-(0.98±0.16)mV。岩白菜素在Ber-MM中转变为无定形态,TEM结果显示Ber-MM外貌为类球形。Ber-MM体外释药具有缓释特征,在3种pH介质中均符合Weibull模型。结论:Ber-MM粒径小,药物控释效果明显,可为后续临床开发奠定基础。

OBJECTIVE To prepare bergenin Soluplus/TPGS mixed micelles(Ber-MM)and evaluate drug release behavior in vitro.METHODS Thin film hydration method was used to prepare Ber-MM.Envelopment efficiency and drug loading were used as evaluation indexes,Box-Behnken response surface design method was employed to optimize the formulation of Ber-MM,and its lyophilized powder was also prepared.X-ray powder diffraction(XRPD)was used to analyze the crystal form in Ber-MM.Transmission electron microscope(TEM)was employed to observe its microscopic appearance.Release behavior of Ber-MM in pH1.2,pH4.5 and pH6.8 media was studied by dialysis method,and the release model was also fitted.RESULTS The optimal formulation of Ber-MM was as follows:the ratio of Soluplus/TPGS was 8.3∶1,the ratio of carrier to drug was 8.8∶1,and the hydration volume was 20.5 mL.The envelopment efficiency,drug loading,particle size and Zeta potential was(93.56±1.34)%,(9.50±0.18)%,(71.19±4.08)nm and-(0.98±0.16)mV,respectively.XRPD results showed that bergenin was changed into an amorphous form in Ber-MM.Ber-MM was spherical in appearance observed by TEM.Drug release of Ber-MM in vitro had obvious sustained-release characteristics,and the release model was consistent with Weibull model in the three kinds of pH media.CONCLUSION The size of Ber-MM is small,and the drug controlled release effect is obvious,which lays the foundation for subsequent clinical development.