辛伐他汀片溶出曲线相似性评价及有区分力溶出度检测方法的研究

Similarity Evaluation of Dissolution Curves of Simvastatin Tablets and Study on Dissolution Method with Discriminatory Power

目的考察国产与原研辛伐他汀片体外溶出曲线的相似性,建立有区分力的溶出度检查方法。方法采用日本橙皮书与中国药典的试验条件,使用相似因子法评价国产与原研片溶出曲线的相似性;有区分力的溶出度检查方法为:桨法,50 r·min^(-1),溶出介质为900 mL含0.4%十二烷基硫酸钠的pH 7.0磷酸盐缓冲液,30 min取样,HPLC测定,限度为标示量的80%。结果以日本橙皮书与中国药典的溶出度方法测定,国产与原研片剂溶出曲线相似,没有区分力。新建立的溶出度检查方法显示,原研和国产片剂溶出曲线有显著不同,在30 min时溶出量出现显著差异。结论溶出介质中的十二烷基硫酸钠浓度是建立辛伐他汀片具有区分力溶出度方法的关键,本研究可为仿制药质量一致性评价提供试验依据。

OBJECTIVE To study the similarity of the dissolution curves between original and generic simvastatin tablets, and establish a distinguishable dissolution method. METHODS The experimental condition of dissolution methods in Japanese orange book and Chinese Pharmacopoeia were adopted. With the original drug in parallel, the dissolution curves of generic tablets were compared by the similarity factor method. Meanwhile, the new discriminative dissolution method was developed as follows： paddle stirring at 50 r·min^-1, pH 7.0 phosphate buffer solution（900 mL） containing 0.4% SDS as dissolution medium, HPLC analysis after 30 min, and the limit was set at 80%. RESULTS The experimental conditions following the Japanese orange book and Chinese Pharmacopoeia could not discriminate the original and generic tablets. The newly established method could afford a significant difference at 30 min. CONCLUSION The concentration of SDS in the dissolution medium is found to be essential, and even the key to discriminate the dissolution behavior of simvastatin tablets. This result provides the experimental basis for consistency evaluation.