去甲斑蝥素纳米混悬剂的制备与质量评价  

Preparation and quality evaluation of norcantharidin nanosuspensions

作　　者：张淼[1] 何瑶[1] ZHANG Miao;HE Yao(Xianyang Vocational College, Xianyang 712000, China)

机构地区：[1]咸阳职业技术学院

出　　处：《国际药学研究杂志》2019年第3期211-217,共7页Journal of International Pharmaceutical Research

摘　　要：目的采用介质碾磨法制备去甲斑蝥素纳米混悬剂(Ncr-NS),并评价其质量。方法以羟丙基纤维素(HPC-SL浓度(X1)、碾磨速度(X2)和碾磨介质ZrO2直径(X3)作为Ncr-NS的处方和工艺参数,以碾磨120 min后Ncr-NS的平均粒径作为评价指标,使用Box-Behnken实验设计优化其处方和工艺参数;采用激光粒度仪测定粒径分布和Zeta电位,扫描电镜观察其微观形态;比较微粉化Ncr原料药与Ncr-NS的体外溶出速率。结果实验优化得到的Ncr-NS最优处方和工艺参数如下:HPC-SL浓度为22%,碾磨速度为750 r/min,碾磨介质直径为0.6 mm。所制备的Ncr-NS平均粒径为(325.4±4.1)nm,多聚分散系数(PDI)为(0.184±0.009),Zeta电位为(-32.5±1.8)mV;扫描电镜下显示Ncr-NS为椭圆状球形,粒径分布较为均匀。在90 min时Ncr-NS的体外释放度是Ncr原料药的2.27倍。结论本研究采用介质碾磨法制备的Ncr-NS体外释放速率快,有望提高其口服生物利用度。Objective To prepare norcantharidin nanosuspensions(Ncr-NS)by wet media milling method and evaluate their quality. Methods The hydroxypropyl cellulose-SL(HPC-SL)concentration(X1),the milling rate(X2)and the diameter of ZrO2 milling media(X3)were set as the parameters of the influencing factors on the Ncr-NS formulation and preparation. The Box-Behnken experimental design was used to optimize the formulation and process parameters using the average particle size of Ncr-NS as an indicator.The particle size distribution and Zeta potential were measured by the laser particle size analyzer,and the microscopic morphology was observed by the scanning electron microscopy. The in vitro dissolution of micronized Ncr drug substance and Ncr-NS was compared.Results The optimal formulation and process parameters for Ncr-NS were:the HPC-SL concentration 22%,the milling speed 750 r/min,and the ZrO2 milling media diameter 0.6 mm. The average particle size of Ncr-NS was(325.4±4.1)nm,the polydispersity index(PDI)was(0.184±0.009),and the Zeta potential was(-32.5±1.8)mV. The particle size distribution of Ncr-NS was uniform as observed by the scanning electron microscopy. The in vitro dissolution of Ncr-NS was 3.27 times that of the micronized Ncr drug substance at 90 min. Conclusion The present Ncr-NS prepared by the wet media milling method showed a rapid dissolution rate in vitro,with the potential to improve the oral bioavailability of Ncr.

关 键 词：去甲斑蝥素 纳米混悬剂 介质碾磨法 口服生物利用度 

分 类 号：R94[医药卫生—药剂学]