药学学报, 2014, 49(8): 1155-1161
引用本文:
潘瑞雪, 高源, 陈万里, 李玉兰, 胡昌勤. 溶出度实验结合计算机模拟技术评价国产阿莫西林胶囊的生物等效性[J]. 药学学报, 2014, 49(8): 1155-1161.
PAN Rui-xue, GAO Yuan, CHEN Wan-li, LI Yu-lan, HU Chang-qin. Dissolution testing combined with computer simulation technology to evaluate the bioequivalence of domestic amoxicillin capsule[J]. Acta Pharmaceutica Sinica, 2014, 49(8): 1155-1161.

溶出度实验结合计算机模拟技术评价国产阿莫西林胶囊的生物等效性
潘瑞雪1, 高源2, 陈万里2, 李玉兰3, 胡昌勤1
1. 中国食品药品检定研究院, 北京 100050;
2. 贵州省食品药品检验所, 贵州 贵阳 550000;
3. 深圳市药品检验所, 广东 深圳 518057
摘要:
对上市仿制药品生物等效性的再评价是当前的研究热点。生物等效性实验是评价仿制药物治疗效果一致性的理想方法,而基于BCS(biopharmaceutical classification system) 理论的体外溶出度实验是最能替代药物体内生物等效性研究的体外试验方法。本文采用常规的溶出度测定方法和开放式流通池法考察国产阿莫西林胶囊在不同介质中的溶出行为,开放式流通池法更能体现其体内的释放特征。流通池法结果显示,国产阿莫西林胶囊存在两种不同的溶出特性。采用Gastro PlusTM软件模拟药物在体内具有不同释放速率(t85%=15~180 min) 时的体内吸收(Cmax和AUC) 情况,发现释放速率在延长至t85%=45 min时,口服阿莫西林胶囊同口服阿莫西林溶液仍具有生物等效性。具有不同溶出特性的国产阿莫西林胶囊45 min内的累积溶出度均可达到85% 以上,模拟计算也提示其在体内具有生物等效性,提示国产阿莫西林胶囊具有生物等效性。
关键词:    一致性评价      阿莫西林      生物药剂学分类系统     
Dissolution testing combined with computer simulation technology to evaluate the bioequivalence of domestic amoxicillin capsule
PAN Rui-xue1, GAO Yuan2, CHEN Wan-li2, LI Yu-lan3, HU Chang-qin1
1. National Institutes for Food and Drug Control, Beijing 100050, China;
2. Guizhou Institutes for Food and Drug Control, Guiyang 550000, China;
3. Shenzhen Institutes for Drug Control, Shenzhen 518057, China
Abstract:
Re-evaluation of bioequivalence of generic drugs is one of the key research focus currently. As a means to ensure consistency of the therapeutic effectiveness of drug products, clinical bioequivalence has been widely accepted as a gold standard test. In vitro dissolution testing based on the theory of the BCS is the best alternative to in vivo bioequivalence study. In this article, the conventional dissolution method and flow-through cell method were used to investigate the dissolution profiles of domestic amoxicillin capsules in different dissolution media, and the absorption behavior of the drugs with different release rates (t85%=15-180 min) in the gastrointestinal tract was predicted by Gastro PlusTM. The flow-through cell method was thought better to reflect the release characteristics in vivo, and amoxicillin capsules with regard to the release rates up to 45 min (t85%=45 min) were having a satisfied bioequivalence with the oral solution according to the Cmax and AUC. Although two different dissolution profiles of domestic amoxicillin capsules were found by flow-through cell methods, prediction results revealed that domestic capsules were probably bioequivalent to each other.
Key words:    drug re-evaluation    amoxicillin    biopharmaceutical classification system   
收稿日期: 2014-01-20
通讯作者: 胡昌勤 Tel:86-10-67095308,Fax:86-10-65115148,E-mail:hucq@nicpbp.org.cn
Email: hucq@nicpbp.org.cn
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