药用辅料硅酸镁铝质量研究及标准修订

Quality Research and standard revision of magnesium aluminum silicate for pharmaceutical excipients

目的:修订《中国药典》2015年版四部中硅酸镁铝的质量标准。方法:通过多种形式的调查研究,掌握了解作为药用辅料的硅酸镁铝的关键质量属性;通过文献研读和标准比对,聚焦本品《中国药典》标准与欧美药典标准在项目设置、测定方法、限度规定等方面的异同;通过实验手段,验证或优化相关质量属性的测定方法,并用于测定代表性的样品,在此基础上,设定合理的限度指标。结果:(1)修订了对来源描述:标准比对发现中外药典来源规定差异较大,《中国药典》2015年版规定为膨胀性较差的双层结构高岭石,而欧美药典规定其来源膨胀性好的三明治式三层结构的蒙脱石和皂石;(2)增订了鉴别方法:《中国药典》2015年版中鉴别的专属性较差,参考USP增加了X-粉末衍射法,分别对4个厂家不同类型的硅酸镁铝采用薄膜法和粉末法进行测定;(3)修订了用于考察产品功能的旋转黏度测定法,对19批国内外药用辅料硅酸镁铝进行测定,发现79%批次在规定限度内,国内外产品在该功能性指标方面略有差异;(4)修订了含量测定方法:采用《中国药典》2015年版的滴定法测定铝镁含量及比例,发现进口样品的所有含量测定结果均不合格,采用新建立的ICP-OES方法对23批样品进行测定,发现国产硅酸镁铝的铝镁比均不在规定范围内,而进口硅酸镁铝均在规定范围内。采用配对t检验对比了USP中的原子吸收光谱法测定硅酸镁铝中镁铝比的数据,Sig=0.655,两者无显著性差异。结论:《中国药典》2015年版的硅酸镁铝标准存在一定缺陷,本研究结果对其进行了修订,并已收载于《中国药典》2020年版中。

Objective:Revision of the quality standard of magnesium aluminum silicate in the Chinese Pharmacopoeia 2015Ⅳ.Methods:Through various forms of investigation and research,master the key quality attributes of magnesium aluminum silicate as a pharmaceutical excipient.Through literature study and standard comparison,focus on the similarities and differences between the“Chinese Pharmacopoeia”standard of this product and the EP and USP standards in terms of project setting,measurement methods,limit regulations,etc.By means of experiments,the determination methods of relevant quality attributes were verified or optimized,and used for the determination of representative samples.And on this basis,reasonable limit indicators were set.Results:①Revise the description of the source:the standard comparision found that the source regulation of Chinese and foreign pharmacopoeia are quite different.It was found in the Chinese Pharmacopoeia 2015 stipulates that it was a double-layered kaolinite with poor expansion,while the European and American pharmacopoeia stipulates that its source was a sandwich-type three-layered montmorilloite and saponite with good expansion.②The identification method was updated:the specificity of identification in the Chinese Pharmacopoeia 2015 was poor,and the X-powder diffraction method was added with reference to USP,and the film method and powder method were used to determine different types of magnesium aluminum silicate from 4 manufacture.③Revised the rotational viscosity measurement method used to investigate the function of the product,measured 19 batches of domestic and foreign pharmaceutical excipients magnesium aluminum silicate,and found that 79%of the batches were within the specified limits,and there were slight differences in the functional index between domestic and foreign products.④The content determination method was revised:the content and ratio of aluminum and magnesium were determined by the titration method of the Chinese Pharmacopoeia 2015,and all the content determination results of the imported samples were found to be unqualified.The newly established ICP-OES method was used to determine the 23 batches of samples.It is found that the aluminum-magnesium ratio of domestic magnesium-aluminum silicate is not within the specified range,while the imported magnesium-aluminum silicate is within the specified range.Paired T test was used to compare the ratio of magnesium to aluminum in magnesium silicate determined by atomic absorption spectrometry in USP(Sig=0.655),with no significant difference between them.Conclusion:The magnesium aluminum silicate standard of the Chinese Pharmacopoeia 2015 has certain defects,and the results of this study have been revised and included in the Chinese Pharmacopoeia 2020.