羧甲淀粉钠中氯乙酸残留对马来酸氯苯那敏稳定性的影响

目的探讨羧甲淀粉钠中残留的氯乙酸对马来酸氯苯那敏稳定性的影响。方法测定不同存放条件下羧甲淀粉钠中氯乙酸残留量,以及以此制备的马来酸氯苯那敏制剂中主成分、最大杂质、总杂质含量,考察羧甲淀粉钠中氯乙酸残留与马来酸氯苯那敏降解程度间的相关性。结果各批样品均有不同程度的氯乙酸残留,近20%的样品氯乙酸残留超过0.2%,最高达1.68%。马来酸氯苯那敏对照品在20℃与40℃条件下存放均稳定,无明显杂质产生;相同存放条件下,马来酸氯苯那敏的降解速率随羧甲淀粉钠中氯乙酸含量的增大而提高;氯乙酸含量相同的羧甲淀粉钠样品的放置温度越高,马来酸氯苯那敏的降解速率越快。结论羧甲淀粉钠中氯乙酸对马来酸氯苯那敏的稳定性存在影响,提示在制剂开发中,需关注辅料中氯乙酸对带负电荷或未共享电子对等易发生亲核反应原料药质量的影响。

Effect of Chloroacetic Acid Residue in Sodium Starch Glycolate on the Stability of Chlorphenamine Maleate

Objective To investigate the effect of chloroacetic acid residue in sodium starch glycolate on the stability of chlorphenamine maleate.Methods The residue of chloroacetic acid in sodium starch glycolate under different storage conditions was determined,the content of main components,maximum impurities and total impurities in chlorphenamine maleate preparation prepared by the above sodium starch glycolate,and the correlation between chloroacetic acid in sodium starch glycolate and the degradation degree of chlorphenamine maleate was investigated.Results Chloroacetic acid residues were found in various batches of samples.Chloroacetic acid residues in nearly 20% of samples exceeded 0.2%,and the highest was 1.68%.Chlorphenamine maleate reference substance was stable at 20℃ and 40℃ without obvious impurities.Under the same storage conditions,the degradation rate of chlorphenamine maleate increased with the increase of chloroacetic acid content in sodium starch glycolate.The higher the storage temperature of sodium starch glycolate samples with the same content of chloroacetic acid,the faster the degradation rate of chlorphenamine maleate.Conclusion Chloroacetic acid in sodium starch aglycolate has an effect on the stability of chlorphenamine maleate,which suggests that attention should be paid to the effect of chloroacetic acid in excipients on the quality of active pharmaceutical ingredients prone to nucleophilic reaction with negative charge or unshared electron equivalence during the development of preparations.