DOC《此论文已发表于《食品与药品》2018年第2期》

此论文已发表于《食品与药品》2018年第2期 盐酸地芬尼多片体外溶出一致性评价研究 唐小鹏,陈莉,陈珉珉,欧阳春华 (株洲市食品药品检验所,湖南 株洲 412011) 摘要:目的 考察盐酸地芬尼多片国产仿制药与原研药的体外溶出一致性.

方法 采用高效液相色谱法(HPLC)测定盐酸地芬尼多在不同溶出介质中的溶解度,绘制溶解度曲线.测定A、B、C三厂家自研剂与原研药在4种不同溶出介质(pH 1.2盐酸溶液、pH 4.0醋酸盐溶液、pH 6.8磷酸盐溶液、水)中的溶出度,分别绘制溶出曲线,并采用相似因子(f2)法对自研剂和原研剂的溶出曲线进行拟合分析.结果 A、B、C三厂家国产仿制药在pH 1.2盐酸溶液、pH 4.0醋酸盐溶液、水中的溶出行为与原研药一致,而在pH 6.8磷酸盐溶液中,仅B厂产品与原研药溶出曲线一致.结论 部分国产仿制药尚需进行工艺改进,以达到与原研药体外溶出一致. 关键词:盐酸地芬尼多片;

体外溶出;

一致性评价;

相似因子(列出3~6个关键词) 中图分类号:R943 文献标识码:A 文章编号:1672-979X(2018)00-0000-00 Consistency Evaluation of the In Vitro Dissolution of Difenidol Hydrochloride Tablets TANG Xiao-peng, CHEN Li, CHEN Min-min, OU YANG Chun-hua, (Zhuzhou Institute for Food and Drug Control, Zhuzhou 412011, China) Abstract: Objective To research the in vitro dissolution consistency between the generic and original preparations of Difenidol Hydrochloride Tablets. Methods The solubility of difenidol hydrochloride in different dissolution mediums were determined by HPLC, and the solubility curves were drawn. The dissolution of the generic preparations from A, B, C companies and the original preparation in

4 different dissolution mediums (pH 1.2 hydrochloric acid solution, pH 4.0 sodium acetate solution, pH 6.8 phosphate solution, water) were determined, then the dissolution curves of those preparations were drawn, and the similarity factors (f2) were calculated to evaluate the in vitro dissolution consistency between the generic and original preparations. Results The dissolution properties of the generic preparations from A, B, C companies were similar to the original preparation in pH 1.2 hydrochloric acid solution, pH 4.0 sodium acetate solution and water. But in pH 6.8 phosphate solution, only the preparation B has similar dissolution curve to original preparation. Conclusion Some generic preparations need to be improved in order to have the same in vitro dissolution as original preparation. Key Words: Difenidol Hydrochloride Tablets;

in vitro dissolution;

consistency evaluation;

similarity factor 盐酸地芬尼多片用于防治多种原因引起的眩晕、恶心、呕吐,原研厂家为日本新药工业株式会社,目前国内已批准注册的生产企业为41家.为提升国内制药行业的整体水平,国家从2012年开始推出仿制药的质量一致性评价[1].相比复杂、昂贵的体内生物等效性评价,体外溶出度一致性评价简单方便、灵敏度高,用体外溶出度一致性评价对仿制药进行筛选,能大大提高体内生物等效性评价的成功率.多种pH值体外溶出曲线的测定能全方位地反映仿制药与原研药在不同介质中的溶出行为差异,是国内外评价口服固体制剂品质的重要手段[2-3].本文参照日本橙皮书公布的盐酸地芬尼多片的溶出度测定方法,考察了国产仿制药在4种不同介质中的溶出曲线,并采用相似因子法(f2)对国产仿制药和原研药进行评价. 仪器与试药 1.1 仪器 AG-135电子分析天平(梅特勒-托利多);