市售二至丸水蜜丸和配方颗粒的体外溶出度比较

Comparison Between in Vitro Dissolution of Two Kinds of Commercially Available Erzhi Wan Preparations

目的:考察二至丸水蜜丸和配方颗粒中5种药效活性成分的溶出情况,比较这些成分在2种剂型中的体外溶出特点。方法:参照《中国药典》2010年版二部附录X C溶出度测定法,采用第二法桨法,转速75 r·min-1,测试不同溶出介质(水,30%乙醇,0.1 mol·L-1盐酸和p H 4.5,6.8的磷酸盐缓冲液)。利用UPLC测定2种剂型中红景天苷、特女贞苷、女贞苷、木犀草素和齐墩果酸5种药效成分的体外溶出度,比较2种制剂的溶出行为。结果:在各个溶出介质中,二至丸2种不同制剂中各活性成分的溶出行为差别很大,配方颗粒中红景天苷、特女贞苷、女贞苷在各个介质里都能快速溶出且溶出量高(>85%);而水蜜丸中木犀草素和齐墩果酸只能在p H 6.8磷酸盐缓冲液中溶出很少的量(<30%)。从差异因子和相似因子分析,2种制剂中相同成分的溶出曲线无相似性。结论:和水蜜丸相比,配方颗粒中活性成分的累积溶出量更高,且在同一种溶出介质中,能溶出更多的药效成分。说明在体外溶出方面,配方颗粒这种新型的中药形式具有更大的优势。建立的溶出度方法可以应用于二至丸制剂的质量控制。

Objective： To investigate in vitro dissolution of five active ingredients in water-honeyed pills and dispensing granules of Erzhi Wan, and to compare dissolution behavior of five ingredients in these two preparations. Method： In vitro dissolution of Erzhi Wan was studied in formulations of water-honeyed pills and dispensing granules in different media（ water,30% ethanol,0. 1 mol·L- 1HCl,PBS with p H of 4. 5 and 6. 8）by following the 2010 edition of Chinese Pharmacopoeia through the second method（ the paddle method）,rotation speed was set 75 r·min- 1. UPLC was developed and validated to detect simultaneously in vitro dissolution of five active ingredients（ salidroside,specnuezhenide,nuezhenoside,luteolin,oleanolic acid）. Different parameters were employed to evaluate dissolution characteristics of these two preparations. Result： In different dissolution media,dissolution behavior of five ingredients in these two preparations had great difference. Salidroside,specnuezhenide and nuezhenoside in dispensing granules could dissolve fast and had high dissolution percentages（ 85%） in each medium. Luteolin and oleanolic acid in water-honeyed pills dissolved very little（ 30%） only in PBS with p H 6. 8. Form difference factor of f1 and similarity factor of f2,the same ingredient in these two preparations had different dissolution behavior. Conclusion： Compared with water-honeyed pills, active ingredients in dispensing granules have a higher cumulative dissolution, and in the same medium, medicinal ingredient can be dissolved more. Dispensing granules has great advantage in the aspect of in vitro dissolution.This developed method can be applied for quality control of Erzhi Wan preparations.