摘要
目的为罗库溴铵注射液的产品开发和申报提供参考。方法根据Arrhenius方程,设计不同温度条件下注射液的加速试验,考察水解降解杂质的增长情况,计算杂质生成反应活化能,预测产品长期稳定条件下的有效期。结果杂质V能生成所需活化能为81191.2 J/mol,(5±3)℃条件下长期储存,其生成反应速率常数最高为5.96×10^(-7)mol/(L·h),至少需要60个月才达到2015年版《中国药典(二部)》规定的限度值(≤2.0%),且24个月长期稳定性试验结果与预测结果基本一致。结论杂质V含量是罗库溴铵注射液限度标准中超标风险最高的检测项,其水解降解杂质的降解速率决定产品的有效期,其稳定性预测结果足够支持药品说明书规定的36个月有效期。该方法适用于罗库溴铵注射液水解降解杂质含量的预测研究。
Objective To provide a reference for the development and registration of Rocuronium Bromide Injection.Methods According to the Arrhenius equation,the accelerated test of injection at different temperatures was designed to investigate the growth of hydrolytic degradation impurities,calculate the activation energy of impurity formation reaction,and predict the validity period of the product under long-term stable conditions.Results The activation energy required for the formation of impurityⅤwas 81191.2 J/mol,and its highest reaction rate constant was 5.96×10^(-7)M/(L·h)under the long-term storage condition at(5±3)℃,which meant that it took at least 60 months to reach the limitation(≤2.0%)specified in the Chinese Pharmacopoeia(2015 Edition,VolumeⅡ).The 24-month long-term stability test results were consistent with the predicted results.Conclusion The content of impurityⅤis the highest risk item in the limit standard of the product.The degradation rate of hydrolytic degradation impurity determines the validity period of the product.The stability prediction results of the product are enough to support the 36-month validity period specified in the drug package inserts.This method is suitable for predicting the content of hydrolytic degradation impurities in Rocuronium Bromide Injection.
作者
付强
柯锐
朱柄甲
徐兴志
刘君洋
王志云
陆伟跃
FU Qiang;KE Rui;ZHU Bingjia;XU Xingzhi;LIU Junyang;WANG Zhiyun;LU Weiyue(Zhejiang Huahai Pharmaceutical Co.,Ltd.,Taizhou,Zhejiang,China 317000;School of Pharmacy,Fudan University,Shanghai,China 201303)
出处
《中国药业》
CAS
2021年第9期59-62,共4页
China Pharmaceuticals
