市售双氯芬酸钠肠溶片质量分析与杂质风险评价

Quality Analysis and Impurity Risk Assessment of Commercially Available Diclofenac Sodium Enteric-coated Tablets

目的对市售双氯芬酸钠肠溶片进行质量分析,为提高产品质量的均一性和优化有关物质的检测方法提供参考。方法采用法定检验方法对29批双氯芬酸钠肠溶片进行全项检验,并对检验结果进行统计分析;测定9个厂家样品的溶出曲线,找出仿制样品体外溶出行为与原研药物的差异;建立潜在风险物质杂质B的定量测定方法,并通过了方法学验证,将建立的方法应用于双氯芬酸钠肠溶片的有关物质分析。结果29批样品按法定标准检验均合格,但各厂家样品在有关物质和溶出度两个项目上呈现较大差异。与A厂家样品比较,B厂家和H厂家样品的溶出曲线存在明显差异,提示存在临床疗效不一致的风险。B厂家样品采用新建立的杂质定量测定方法分析样品的总杂质,结果超出了标准规定的限值,提示存在一定安全性风险。结论双氯芬酸钠肠溶片的总体质量较好,但部分厂家仍需进一步加强质量研究和控制,建议优化有关物质的检查方法以提高检验标准对产品质量的区分力。

Objective To investigate the quality of commercially available diclofenac sodium enteric-coated tablets,so as to provide a reference for improving the homogeneity of product quality and the method of impurity quantitation.Methods 29 batches of diclofenac sodium enteric-coated tabletswere tested by statutory inspection test,and the results were analyzed statistically.Besides,the release curves of diclofenac sodium enteric-coated tablets from 9 manufacturers were investigated to describe the different in-vitro-dissolution behavior between the generic drug and the reference listed drug.In addition,a quantitative method of impurity B was established and validated,and applied to the related substances assay.Results All items of 29 samples were in line with the quality standard,but there were differences in related substances and dissolution among differentmanufacturers.The release curves of samples from manufacturer B and H were significantly different from manufacturer A,suggesting the risk of inconsistent clinical efficacy.The total impurities of sample B determined by the newly established impurity quantitation method was exceeded the limit specified in the standard,which indicate a potentially safety risk.Conclusion While the results show that the overall quality of diclofenac sodium enteric-coated tablets was good,the quality research and control still need to be enhanced in some manufacturers.And it is also recommended to optimize the examination method for related substances of inspection standards to better differentiate product quality.