依托孕烯/炔雌醇复方阴道环体外释放方法学研究  

Methodological study on in vitro release of etonogestrel/ethinyl estradiol compound vaginal ring

作　　者：王沙沙 陈攀 曾佳 薛嫚 李芳 潘峰 赵艳红 马诗雨 任福正[1] 柯燕雄[1] 俸灵林 Wang Shasha;Chen Pan;Zeng Jia;Xue Man;Li Fang;Pan Feng;Zhao Yanhong;Ma Shiyu;Ren Fuzheng;Ke Yanxiong;Feng Linglin(East China University of Science and Technology Pharmaceutical Engineering and Process Chemistry Research Center,Shanghai 200237,China;School of Health Science and Engineering,University of Shanghai for Science and Technology,Shanghai 200093,China;NHC Key Lab of Reproduction Regulation,Shanghai Engineering Research Center of Reproductive Health Drug and Devices,Pharmaceutical Formulations and Analysis Laboratory,Institute of Drugs and Medical Devices of Shanghai Institute for Biomedical and Pharmaceutical Technologies,Shanghai 200237,China)

机构地区：[1]华东理工大学制药工程与过程化学教育部工程研究中心,上海200237 [2]上海理工大学生命科学与工程学院,上海200093 [3]国家卫生健康委员会计划生育药具重点实验室、上海生殖健康药具工程技术研究中心、上海市生物医药技术研究院药物与医疗器械研究所药物制剂与分析研究室,上海200237

出　　处：《中华生殖与避孕杂志》2023年第8期813-819,共7页Chinese Journal of Reproduction and Contraception

基　　金：国家重点研发计划(2016YFC1000902);上海市“科技创新行动计划”(22DX1900400)。

摘　　要：目的研制出具有良好缓释性能的依托孕烯(etonogestrel,ENG)/炔雌醇(ethinyl estradiol,EE)复方阴道环,并对其体外释放测定方法学开展研究,确立与实时释放方法具有良好相关性的加速释放方法。方法以乙烯-醋酸乙烯共聚物(ethylene-vinyl acetate copolymer,EVA)为基质,以热熔挤出法制备ENG/EE复方阴道环,建立基于摇瓶法的体外实时释放测定方法和加速释放测定方法,考察该复方阴道环的体外释放行为及释放机制,并对其实时释放经时过程和加速释放经时过程的相关性进行分析。结果所得阴道环外观圆整,表面光滑,在优选出的体外实时释放条件(释放介质:200 mL纯水,37℃恒温水浴振荡器中60 r/min振摇)中缓慢释药,第21天ENG和EE累计释放量分别为54.39%和46.80%,在优选出的体外加速条件(释放介质:200 mL 0.6%十二烷基硫酸钠水溶液,55℃下60 r/min振摇)下药物释放经时过程及其机制与实时释放条件下的拟合结果相关系数均大于0.99。结论本研究研制的ENG/EE复方阴道环的体外缓释效果显著,所建立的加速释放方法与实时释放方法相关性良好,可供此类阴道环产品的质量评价研究及体外释放研究方法指南的制定提供有益参考。Objective To develop an etonogestrel(ENG)/ethinyl estradiol(EE)compound vaginal ring with good sustained-release properties,studying its in vitro release assay methodology,and establishing an accelerated release method with good correlation with real-time release methods.Methods Ethylene-vinyl acetate copolymer(EVA)was used as the matrix to prepare ENG/EE compound vaginal ring by hot melt extrusion method,and an in vitro real-time release assay method and an accelerated release assay method based on shake flask method were established.The in vitro release behavior and release mechanism of ENG/EE compound vaginal ring were investigated,and the correlation between real-time release and accelerated release over time was analyzed.Results The obtained vaginal ring had a round appearance and a smooth surface,and the drug was slowly released under the optimal real-time release conditions in vitro(release medium:200 mL of pure water,shaking at 60 r/min in a constant temperature water bath shaker at 37℃),and the cumulative release of ENG and EE on the 21st day were 54.39%and 46.80%,respectively.The correlation coefficients of drug release and its mechanism under the optimized in vitro accelerated conditions(release medium:200 mL of 0.6%sodium dodecyl sulfate aqueous solution,shaking at 60 r/min at 55℃)with the results under real-time release conditions were all greater than 0.99.Conclusion The ENG/EE compound vaginal ring obtained in this study has a significant in vitro sustained-release effect,and the established accelerated release conditions have a good correlation with real-time release conditions,which can provide a useful reference for the quality evaluation research of such vaginal ring products and the formulation of guidelines for in vitro release research methods.

关 键 词：依托孕烯 炔雌醇 阴道环 实时释放 加速释放 相关性 

分 类 号：R169.41[医药卫生—公共卫生与预防医学]