ω-3脂肪酸乙酯90软胶囊溶出度测定方法的建立和溶出曲线相似性评价  

Establishment of dissolution method and similarity evaluation of dissolution curves of omega-3-acid ethyl ester 90 soft capsules

作　　者：申潜 董海丽 张翕 刘晓佳 吴鸳鸯 阮昊 SHEN Qian;DONG Hai-li;ZHANG Xi;LIU Xiao-jia;WU Yuan-yang;RUAN Hao(Zhejiang Institute for Food and Drug Control,NMPA Key Laboratory for Core Technology of Generic Drug Evaluation,Hangzhou 310052,China;Hangzhou Institute for Food and Drug Control,Hangzhou 310022,China;Department of Pharmaceutical Analysis,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]浙江省食品药品检验研究院、国家药监局仿制药评价关键技术重点实验室,杭州310052 [2]杭州市食品药品检验科学研究院,杭州310022 [3]中国药科大学药物分析系,南京211198

出　　处：《药物分析杂志》2024年第12期2180-2188,共9页Chinese Journal of Pharmaceutical Analysis

基　　金：浙江省药品监督管理局科技计划项目(2023019);浙江省基础公益研究计划项目(LGC22H300003)。

摘　　要：目的:建立流池法测定ω-3脂肪酸乙酯90软胶囊的溶出度,考察不同企业样品溶出行为的差异。方法:考察溶出介质(表面活性剂的种类和浓度、pH、胃蛋白酶的用量)、流速和系统模式(开/闭环)对ω-3脂肪酸乙酯90软胶囊溶出行为的影响,建立HPLC法对各取样点的溶出量进行测定,并通过计算相似因子(f_(2))评价仿制制剂和参比制剂溶出曲线的相似性。结果:采用流池法的闭环模式,栓剂池,以含4.0%曲拉通X-100的0.01 mol·L^(-1)盐酸溶液为溶出介质,流速为2.0 mL·min^(-1),该溶出方法对产品质量和不同处方有较好的区分力。结论:建立的溶出方法可用于ω-3脂肪酸乙酯90软胶囊的质量控制,能为ω-3脂肪酸乙酯90软胶囊的一致性评价及油脂类软胶囊的溶出方法开发提供参考。Objective:To develop a flow-through cell method for the dissolution test of omega-3-acid ethyl ester 90 soft capsules and compare the dissolution behaviors from different manufacturers.Methods:The medium(surfactant and its concentration,pH,dosage of pepsin),flow rate and system mode(closed versus open)were investigated.The samples were collected at the specified time and determined by HPLC.The similarity of the dissolution curves between generic drugs and reference listed drug was evaluated by similarity factor(f_(2)).Results:A closed-loop mode of flow-through cell apparatus was employed,with 0.01 mol·L^(-1)hydrochloric acid solution containing 4.0%Triton X-100 as the dissolution medium,and the flow rate was 2.0 mL·min^(-1).The dissolution curves of the samples that have passed consistency evaluation are similar to those of the reference and the samples produced by enterprise in the declaration stage are partly similar.The method has effective distinguish ability for product quality and different prescriptions.Conclusion:The newly established method can be used for the quality control of omega-3-acid ethyl ester 90 soft capsules,and can provide references for further consistency evaluation and the dissolution method development of lipid-filled soft gelatin capsule(SGC).

关 键 词：ω-3脂肪酸乙酯90软胶囊 流池法 溶出曲线 区分力 一致性评价 二十碳五烯酸乙酯 二十二碳六烯酸乙酯 

分 类 号：R917[医药卫生—药物分析学]