基于EVA材料的米非司酮阴道环处方研究及释药机制探索  

Prescription research and release mechanism of mifeipristone EVA intravaginal ring

作　　者：董健 马彬 伍思怡 宁美英 DONG Jian;MA Bin;WU Siyi;NING Meiying(National Research Institute for Family Planning,Beijing 100081;Graduate School of Peking Union Medical College)

机构地区：[1]国家卫生健康委科学技术研究所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

出　　处：《中国计划生育学杂志》2023年第8期1769-1776,共8页Chinese Journal of Family Planning

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资助(2022GJZ04)。

摘　　要：目的:制备可用于女性子宫肌瘤术前预处理或长效管理的米非司酮乙烯-醋酸乙烯酯(EVA)阴道环,进行处方优化,考察体外释放度,并对米非司酮EVA阴道环的释药机制进行初步探讨。方法:通过热熔挤出及共挤出方法分别制备米非司酮EVA基质型及储库型阴道环。测定米非司酮在不同溶出介质中的饱和溶解度,选定合适的溶出介质。使用桨法测定阴道环体外释放度,使用单因素考察法考察阴道环不同参数对体外释放度的影响。总结阴道环体外释放度规律,拟合阴道环体外释放公式。结果:选定EVA28药芯+EVA18控释膜与EVA33药芯+EVA28控释膜制备米非司酮储库型阴道环,两种阴道环的膜厚度均为0.03 mm,药芯直径均为6.3 mm,日均释药量(MDR)分别达4.16 mg/d与4.54 mg/d。阴道环体外释放度公式与实验结果匹配良好。结论:制备的阴道环体外释放度可满足用于子宫肌瘤长期管理的米非司酮小剂量长效给药需求。拟合的阴道环体外释放度公式在一定程度上可指导阴道环处方优化工作。Objective:To prepare a mifepristone EVA intravaginal ring used for preoperative pretreatment or long-term management of women with uterine fibroids,to optimize the prescription of the intravaginal ring,to investigate the in vitro release rate of mifepristone of the intravaginal ring,and to preliminarily explore the mifepristone release mechanism of the intravaginal ring.Methods:Mifepristone EVA matrix type and reservoir type intravaginal rings were prepared by hot melt extrusion and coextrusion methods,respectively.The saturation solubility of mifepristone in dif-ferent dissolution media was measured to select the appropriate dissolution medium.The paddle method was used to determine the in witro release of mifepristone from the intravaginal ring.The single factor examination method was usod to investigate the influence of the different parameters of the intraveginal ring on the in vitro release of mifepris-tone.The regularity of the in vitro release of mifepristone from intravaginal rings was summarized,and the formula of the in vitro release of mifepristone was fitted.Results:EVA28+EVA18 and EVA33+EVA28 were selected to pre-pare mifepristone reservoir type intravaginal ring.The membrane thickness and the diameter of drug cores of the two intravaginal rings were 0.03 mm and 6.3 mm.The average daily drug release(MDR)of mifepristone of the EVA28+EVA18 and EVA33+EV A28 mifepristone reservoir type intravaginal rings were 4.16 mg/d and 4.54 mg/d.The for-mula of the in vitro release of mifepristone intravaginal rings matches well with the experimental results.Conclusion:The in vitro release of mifepristone from the prepared intravaginal ring can meet the demand of low-dose administration of mifepristone for long term management of uterine fibroids.The ftted formula of the mifepristone in vitro release from the intravaginal rings can guide the optimization of the intravaginal ring prescription to a certain extent.

关 键 词：子宫肌瘤 阴道环 米非司酮 乙烯-醋酸乙烯酯 

分 类 号：R943[医药卫生—药剂学]