应用改进的质量评价方法考察复方丹参制剂

Application of improved quality evaluation method to Fufang Danshen products

目的:应用改进的质量评价方法考察复方丹参制剂,为其现行质量标准改进提供参考。方法:选取水溶性部分丹参素、原儿茶醛、丹酚酸B及脂溶性部分隐丹参酮、丹参酮ⅡA共5种指标成分,对6个厂家的复方丹参制剂进行含量、溶出度和稳定性测定,比较相同制剂不同厂家、相同厂家不同批次间的含量差异。以相似因子法评价溶出曲线、用动力学过程描述各指标成分含量变化规律并推算有效期。结果:所有厂家的复方丹参市售品中指标成分的含量均超出中国药典规定含量下限。水溶性成分的含量变化大于脂溶成分,在溶出度试验中,水溶性成分大多溶出,而脂溶性成分未能测量到。f2值显示各厂家产品中没有相同溶出度。加速和长期试验,5个指标成分降解符合一级动力学过程,预测的有效期均小于产品标示保持期。结论:现行的复方丹参制剂质量标准应增加指标成分数量、增加指标成分的含量上限规定、增加溶出度和稳定性考察项目。

AIM：To apply improved quality evaluation method for improving current quality criteria of Fufang Danshen products. METHODS：Considering both hydrophilic and lipophilic active components-danshensu,protocatechuic aldehyde,salvianolic acid B,cryptotanshinone and tanshinone ⅡA were selected as five markers. A HPLC method was developed to simultaneously determine their contents,which were used to compare the products from different companies,and different batches from the same company. Similarity factor method was used to evaluate the similarities of in-vitro dissolution profiles. Moreover, accelerated and long-term stability tests were performed to predict the shelf-life of Fufang Danshen products. RESULTS： All of the Fufang Danshen products passed the content requirements of Chinese Pharmacopeia. However, the content variations of the hydrophilic components were much higher than those of the lipophilic components. In dissolution tests, most of the hydrophilic components were dissolved completely while all of the lipophilic components could not be detected. Tile f2 values showed that there were no similar dissolution profiles among different brands of Fufang Danshen products. The contents of five markers degraded compatible with first-order kinetics processes in both the accelerated and long-term stability tests. The predicted shelf-life of Fufang Danshen products were shorter than those labelled on the products. CONCLUSION ： It is suggested that more markers with defined content range instead of lower content limit are required for better control of Fufang Danshen products. Dissolution and stability tests need to be added into the quality control criteria in the Chinese Pharmacopeia.