定制热熔挤出阴道环设备在黄体酮阴道环制备中的应用与效果分析  

Application and efficacy of a customized intravaginal ring device of hot-melt extrusion progesterone

作　　者：伍思怡 马彬 董健 宁美英 WU Siyi;MA Bin;DONG Jian;NING Meiying(NHC Key Laboratory of Reproductive Health Engineering Technology Research,Beijing 100081,China;Graduate School,Peking Union Medical College,Beijing 100730¸China)

机构地区：[1]国家卫生健康委生殖健康工程技术研究中心,北京100081 [2]北京协和医学院研究生院,北京100730

出　　处：《中国医院药学杂志》2024年第17期1975-1979,共5页Chinese Journal of Hospital Pharmacy

基　　金：国家卫生健康委科学技术研究所中央级公益性科研院所基本科研业务费专项资金项目(编号:2022GJZ04)。

摘　　要：目的:采用热熔挤出技术制备阴道环(intravaginal ring,IVR),根据IVR的特征和加工性质定制用于阴道环的热熔挤出设备。方法:定制热熔挤出设备,包含挤出系统、造粒系统、包膜系统和冷却固化系统,搭载挤管机头和包膜机头可以实现在该设备上挤出药芯和包覆IVR的控释膜,适用于基质型、储库型等多种IVR的制备。将该设备应用于以乙烯-醋酸乙烯酯共聚物(EVA)为载体的黄体酮储库型IVR的制备中,进行实际的药物制备效果分析。研究设计了多组实验,通过单因素考察法研究不同基质材料、载药量和控释膜厚度的IVR制备,并以桨法测定所得IVR的体外药物体外释放度进而评价本设备的应用效果。结果:定制的热熔挤出IVR设备在制备过程中具有良好的加工性能,成功制备出基质材料为EVA9、EVA16、EVA18、EVA28、EVA33和EVA40、载药量质量分数为10%、20%、30%、40%、控释膜厚度为0.02、0.06、0.08、0.15 mm的黄体酮IVR,所得IVR外观均一,并能实现预期的控释效果,释药稳定。结论:该课题所定制的用于IVR的热熔挤出设备可实现良好的药物制备,结合研究成果,该IVR制备设备为阴道环制剂提供了一种高效、简便的制备方法,可望在IVR领域得到广泛应用。OBJECTIVE To employed hot melt extrusion(HME)technology to prepare intravaginal rings(IVRs)and customize an HME device specifically for IVR production based upon the characteristics and processing properties of IVRs.METHODS The customized HME device consists of extrusion,granulation,coating and cooling-curing systems.Extrusion and coating heads are utilized for extruding drug cores and coating IVRs with controlled-release membranes.This device is suitable for preparing various matrix and reservoir types of IVRs.Levonorgestrel reservoir-type IVRs were prepared with ethylene-vinyl acetate copolymer(EVA)as a carrier material and drug preparation effects analyzed.The effects of different matrix materials,drug loading levels and membrane thicknesses on IVR preparation were examined through a single-factor experimental approach.In vitro drug release of obtained IVRs was determined with a paddle method for evaluating the application effectiveness of this device.RESULTS The customized HME IVR device exhibited excellent processing performance.Levonorgestrel IVRs were successfully prepared with various EVA matrix materials(EVA9,EVA16,EVA18,EVA28,EVA33&EVA40),drug loading levels(10%/20%/30%/40%,wt%)and membrane thicknesses(0.02/0.06/0.08/0.15 mm).The resulting IVRs displayed uniform appearance and achieved the expected controlled-release effects with stable drug release profiles.CONCLUSION The customized HME IVR device enables effective drug preparation.It provides an efficient and straightforward method for intravaginal ring formulation with broad applications.

关 键 词：热熔挤出法 阴道环 固体分散体 缓控释 

分 类 号：R943[医药卫生—药剂学]