溶出度在药品评价中的作用探讨

Discussion on importance of dissolution test method in drug evaluation

本文通过对3个仿制药在研发中与原研药溶出曲线对比及体内生物等效性试验结果的分析,阐述溶出度若要作为评价口服固体制剂的重要指标,选择合适的测定方法非常关键。溶出度方法可分为无区分力、有区分力及有体内预测力的溶出方法(即临床相关的溶出方法)。只有经人体药代数据证明具有体内预测能力的溶出度测定方法,才能用体外溶出曲线对比研究结果来预测仿制药与原研药在体内是否等效或变更前后的产品是否等效。而有区分力的溶出度方法一般仅用于监测同一企业的产品在日常生产中是否会在原辅材料质量与制剂生产工艺等方面发生不可预测的变化,如果用于比较不同企业产品质量则应慎重。

Via comparison of dissolution profiles of three oral solid dosage（ OSD） generic products with those of the originitor＇s brand products as well as analysis of the results of pilot bioequivalence studies,it is illustrated that developing product specific dissolution test method is a critical approach for evaluation of OSD drug products. The dissolution test methods,in general,can be classified into three categories,i. e. non-discriminating dissolution test methods,discriminating dissolution test methods and predictive dissolution test methods（ clinical relevant dissolution test methods）. Only predictive dissolution test methods,which are proven by PK（ BE） studies in human,can be used to predict clinical performance consistency. Discriminating dissolution test methods have the ability to differentiate drug products manufactured under different conditions when there are changes of any raw materials or process variables. It is also noted that it is highly likely that,products displaying different dissolution performance by same dissolution test methods,which are manufactured by different formulations / manufacturers,may have equivalent clinical performance.