坎地沙坦酯P123/F127混合胶束给药系统的构建及表征  

Construction and Characterization of Candesartan Cilexetil P123/F127 Mixed Micelle Delivery System

作　　者：莫一燕 孙敬蒙 房辰晨 贾珍珍 张鑫 张炜煜[1] MO Yiyan;SUN Jingmeng;FANG Chenchen;JIA Zhenzhen;ZHANG Xin;ZHANG Weiyu(College of Pharmacy,Changchun University of Chinese Medicine,Changchun 130117,China;Department of Clinical Pharmacy,the First Hospital of Jilin University,Changchun 130021,China)

机构地区：[1]长春中医药大学药学院,长春130117 [2]吉林大学第一医院临床药学部,长春130021

出　　处：《医药导报》2022年第12期1828-1835,共8页Herald of Medicine

基　　金：吉林省教育科学“十三五”规划课题(GH19135)。

摘　　要：目的制备并优化坎地沙坦酯混合胶束的处方及制备工艺。方法采用薄膜水化法,以泊洛沙姆P123和F127为载体材料制备坎地沙坦酯混合胶束。以包封率、载药量及沉降率为考察指标,运用单因素实验与星点-效应面法优化处方与制备工艺,并对坎地沙坦酯混合胶束进行表征。结果确定优化得到的最佳处方与工艺为:P123/F127混合载体用量为158.2 mg,载体泊洛沙姆P123的质量百分比为66.7%,水化温度为40℃,水相体积为8.40 mL,旋转蒸发温度为45℃,有机溶剂用量为3 mL。所制得的坎地沙坦酯混合胶束的临界胶束浓度值为0.0059 g·(100 mL)^(-1),平均粒径、PDI、Zeta电位分别为(26.39±0.22)nm、0.210±1.49、(-21.57±0.71)mV,其形态为分布均一的规整球形,无聚集。差示扫描量热分析与傅里立叶-红外光谱分析测定结果表明坎地沙坦酯以无定型形式存在于混合胶束中。P123/F127混合胶束可显著提高坎地沙坦酯在纯化水和pH值6.8的缓冲溶液的饱和溶解度。结论该制备工艺方法简单,合理可行。与单一胶束相比,制备得到的坎地沙坦酯混合胶束的处方稳定且包封率和载药量高,可为进一步研究提供参考。Objective To prepare and optimize the formulation and preparation process of Candesartan Cilexetil mixed micelles.Methods Candesartan Cilexetil mixed micelles were prepared by membrane hydration method with pluronic P123 and F127 as carriers.The formulation and preparation process of Candesartan Cilexetil mixed micelles were optimized by single factor experiment and central composite response surface methodology with entrapment efficiency,drug loading,and sedimentation rate as indexes.Results The optimized formulation and process were as follows:The amount of pluronic P123/F127 mixed carrier was 158.2 mg,and the mass percentage of pluronic P123 was 66.7%,the hydration temperature was 40℃,the volume of water phase was 8.40 mL,the rotary evaporation temperature was 45℃,and the amount of organic solvent was 3 mL.The critical micelle concentration of Candesartan Cilexetil mixed micelles was 0.0059 g·(100 mL)^(-1),and the average particle size,PDI,and Zeta potential were(26.39 g±0.22)nm,0.210±1.49,(-21.57±0.71)mV,and its shape was regular spherical with uniform distribution and no aggregation.The results of differential scanning calorimetry(DSC)and Fourier transform infrared spectroscopy(FTIR)showed that Candesartan Cilexetil existed in the mixed micelles in an amorphous form.P123/F127 mixed micelles can significantly improve the solubility of Candesartan Cilexetil in purified water and pH 6.8 Saturated solubility of buffer solution.Conclusion The method is simple,reasonable,and feasible.Compared with single micelle,the formulation of Candesartan Cilexetil mixed micelles was stable,and the entrapment efficiency and drug loading were high,which provided a reference for further research.

关 键 词：坎地沙坦酯 星点设计—效应面法 混合胶束 表征 

分 类 号：R972.4[医药卫生—药品] R943[医药卫生—药学]