复方蒿甲醚本芴醇片溶出度的一致性评价  

Conformance Assessment of Dissolution Curves of Compound Artemether Lumefantrine Tablets in Vitro

作　　者：姚俊娜 杜茂波[2] 易红[2] 李娆娆[2] 张志杰[2] 贾陆[1] 刘淑芝 YAO Jun-na;DU Mao-bo;YI Hong;LI Rao-rao;ZHANG Zhi-jie;JIA Lu;LIU Shu-zhi(Institute of Drug Discovery ＆ Development, Zhengzhou University, Zhengzhou 450001, China;Institute of Chinese Materia, China Academy of Chinese Medical Sciences, Beijing 100700, China)

机构地区：[1]郑州大学药物研究院,郑州450001 [2]中国中医科学院中药研究所,北京100700

出　　处：《中国实验方剂学杂志》2018年第15期43-50,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家“重大新药创制”科技重大专项(2012ZX09202101-005)

摘　　要：目的：考察复方蒿甲醚本芴醇片仿制制剂与参比制剂在4种溶出介质中的溶出度,对二者体外溶出行为的一致性进行评价。方法：按照《中国药典》2015年版（四部）溶出度测定方法桨法,分别对3批仿制制剂和3批参比制剂进行溶出度试验,采用高效液相色谱法（HPLC）和紫外分光光度法（UV）分别测定2种制剂中蒿甲醚和本芴醇在水,p H 1.2（1%氯化苄基二甲基烷基胺的0.1 mol·L-1的盐酸溶液）,p H 2.5（三羟甲基氨基甲烷的盐酸溶液）和p H 4.5（氢氧化钠和柠檬酸的盐酸溶液）4种溶出介质中的溶出曲线,并分别计算3批仿制制剂和3批参比制剂溶出曲线两两之间的相似因子（f2）,分析数据,对各批仿制制剂、仿制-参比制剂溶出曲线的相似性进行比较分析。结果：在所考察的4种溶出介质中,3批仿制制剂之间溶出曲线的相似因子在90-96,均≥90,表明生产工艺较稳定;3批仿制制剂与3批参比制剂的溶出曲线均相似,其相似因子在52-71,均＆gt;50,即2种制剂体外溶出行为一致。结论：3批仿制制剂生产工艺稳定,并与参比制剂的体外溶出行为一致,为进一步研究该仿制制剂提供参考。Objective： To assess the conformance of dissolution behavior of artemether and lumefantrine in compound artemether lumefantrine tablets in four different dissolution media in this study. Method： According to the second method of determination and release in Chinese Pharmacopoia（2015 edition）,the dissolution curves of artemether and lumefantrine in the four dissolution media of water,p H 1. 2（0. 1 mol·L-1 hydrochloric acid solution of 1% benzyl chloride of dimethyl alkyl amine）, p H 2. 5（hydrochloric acid solution of three hydroxymethyl aminomethane） and p H 4. 5（hydrochloric acid solution of sodium hydroxide and citric acid） were determined by high performance liquid chromatography（HPLC） and ultraviolet and visible（UV）spectrophotometry respectively. The method of similarity factor（f2） was used to compare the similarities of dissolution curves of the imitation preparation and the reference preparation. Result： Among the four dissolution media,the similarity factors between the imitation preparations were from 90 to 96, which meant that the production process was stable; the similarity factors between the imitation preparation and the control preparation were from 52 to 71,all greater than 50, which meant that the dissolution curves were similar to each other.Conclusion： The dissolution curves are consistent between the imitation formulations and control formulations in vitro,which provide the basis for further study of the imitation preparations.

关 键 词：复方蒿甲醚本芴醇片 仿制制剂 参比制剂 桨法 高效液相色谱法 紫外分光光度法 溶出曲线 一致性评价 

分 类 号：R284.1[医药卫生—中药学] R289[医药卫生—中医学]