星点设计-效应面法优化鼠尾草酸自微乳载药系统  

Optimization of Carnosic Acid Self-microemulsion Drug Delivery System by Central Composite Design-Response Surface Methodology

作　　者：张丽芬 李凌娜 李蓉 周小魏 何杰[1] 李刚[1] 王振华[1] 马成俊[1] ZHANG Lifen;LI Lingna;LI Rong;ZHOU Xiaowei;HE Jie;LI Gang;WANG Zhenhua;MA Chengjun(Center for Mitochondria and Healthy Aging,School of Life Sciences,Yantai University,Yantai 264005,China)

机构地区：[1]烟台大学生命科学学院/线粒体与健康衰老研究中心,山东烟台264005

出　　处：《烟台大学学报(自然科学与工程版)》2025年第2期208-216,共9页Journal of Yantai University(Natural Science and Engineering Edition)

基　　金：山东省自然科学基金资助项目(ZR2020MH380);烟台市科技创新发展计划项目(2021XDHZ078)。

摘　　要：旨在建立鼠尾草酸自微乳载药系统(CA-SMEDDS)以扩大鼠尾草酸(CA)的临床应用。通过饱和溶解度和伪三元相图初步确定自微乳配方,再利用星点设计-效应面法进一步优化自微乳处方,并对该自微乳的初步稳定性、体外释放、大鼠口服生物利用度进行评价。CA-SMEDDS最佳处方各辅料的质量分数为:油相(油酸乙酯)23.16%、乳化剂(EL-35)54.44%、助乳化剂(PEG400)22.40%。初步稳定性实验表明,CA-SMEDDS在4℃和25℃避光放置条件下稳定性较好;体外释放研究表明,在模拟胃液和模拟肠液的无酶释放介质中,其释放速率均显著高于CA原药;大鼠体内药动学研究结果表明,与CA组相比,CA-SMEDDS相对生物利用度提高了0.86倍。CA-SMEDDS的制备工艺稳定,显著改善了CA的溶出速度,提高了口服生物利用度。This study aimed to establish a carnosic acid self-microemulsion drug delivery system(CA-SMEDDS)to expand the clinical application of carnosic acid(CA).The formula for the self-microemulsion was preliminarily screened by saturation solubility and pseudo-ternary phase diagram and further optimized by central composite design-response surface methodology.The preliminary stability,in vitro release,and oral bioavailability in rats of CA-SMEDDS were also evaluated.The mass fraction of each excipient in the optimal formulation of CA-SMEDDS was as follows:oil phase(ethyl oleate)23.16%,emulsifier(EL-35)54.44%,co-emulsifier(PEG400)22.40%.Preliminary stability experiments showed that CA-SMEDDS were stable at 4℃and 25℃under light-avoiding conditions,and in vitro release experiments showed that their release rate was significantly higher than that of CA in enzyme-free release medium of both simulated gastric and intestinal fluid.The results of the pharmacokinetic study in rats showed that,compared with the CA control group,the relative bioavailability of CA-SMEDDs increased by 0.86 times.The preparation process of CA-SMEDDS was stable,which can significantly improve the dissolution rate and increase the oral bioavailability of carnosic acid.

关 键 词：鼠尾草酸 自微乳给药系统 星点设计 效应面法 体外释放 生物利用度 

分 类 号：R914.5[医药卫生—药物化学]