基于生物热动力学表征的中药固体制剂体外溶出度分析方法初步研究

本文采用微量量热法从生物热活性角度、结合UPLC法, 首次探讨生物检测中药固体制剂体外溶出度的可行性, 旨在弥补单纯化学方法难以客观反映中药固体制剂溶出度检测的不足。以银黄片为模型药, 考察在pH 6.8 (磷酸盐缓冲液) 溶出介质中, 不同溶出时间的银黄片溶出液对金葡菌抑制作用, 测定金葡菌生长代谢热曲线特征谱图, 得到一系列生物热动力学参数, 提出基于生物热活性所得银黄片的累积溶出度, 并与UPLC法测定绿原酸和黄芩苷两个指标成分所得的溶出度运用f₂相似因子法进行相关性评价。结果显示, f₂相似因子均大于50, 表明两方法所测的溶出度具有较好的相关性。生物热活性检测有望成为中药固体制剂的体外溶出度评价手段之一。

An in vitro analytical method based on bio-thermal activity for the determination of dissolution rate of Chinese medicine solid preparation

To explore the new pattern of Chinese medicine solid preparations (CMSP) in vitro dissolution, a method testing the bio-thermal activity in combination with UPLC was used.  Microcalorimetry was used to obtain the characteristic metabolic growth power-time curves and a series of biothermodynamic parameters of the inhibition of Staphylococcus aureus by Yinhuang tablet dissolving solutions at the pH 6.8 (phosphate buffer)  dissolution medium at different times.  From these results, the cumulative dissolution of Yinhuang tablet based on bio-thermal activity was obtained.  The dissolution rates of two components of chlorogenic acid and baicalin were determined by UPLC method.  Then f₂ similar factor method was used to evaluate the relevance of these two methods.  The result showed that f₂ values all were more than 50, indicating that there is a good correlation between the two methods of measuring the dissolution rate.  It is feasible to determine CMSP in vitro dissolution by using bio-thermal activity, and to provide new evaluation methods for controlling the quality of CMSP.