药用辅料聚乙二醇6000与抗癫痫原料药左乙拉西坦的相容性研究  

Study on the compatibility between pharmaceutical excipient polyethylene glycol 6000 and antiepileptic active pharmaceutical ingredients levetiracetam

作　　者：蒋贇 周颖 赵勇 郑金凤 刘雁鸣 JIANG Yun;ZHOU Ying;ZHAO Yong;ZHENG Jinfeng;LIU Yanming(Hunan Institute for Drug Control,Changsha 410001,China;NMPA Key Laboratory for Pharmaceutical Excipients Engineering Technology Research,Changsha 410001,China)

机构地区：[1]湖南省药品检验检测研究院,长沙410001 [2]国家药品监督管理局药用辅料工程技术研究重点实验室,长沙410001

出　　处：《中国药师》2024年第1期57-65,共9页China Pharmacist

基　　金：湖南省自然科学基金科药联合基金项目(2023JJ60106、2022JJ80069)。

摘　　要：目的考察抗癫痫原料药左乙拉西坦与粘合剂聚乙二醇6000之间的相容性,为评估与保障药品的安全性提供依据。方法将左乙拉西坦和不同企业生产的聚乙二醇6000按一定比例混合,依据稳定性影响因素试验方法放样,分别采用差示扫描量热法和HPLC法对左乙拉西坦与聚乙二醇6000的原辅料相容性进行分析,考察热变化、左乙拉西坦性状及有关物质前后的变化。结果在高湿(相对湿度90%)和光照(4500Lx)条件下放置10 d,原辅料相容性较好;在高温50℃和60℃条件下,聚乙二醇6000与左乙拉西坦发生了相互作用,左乙拉西坦杂质A、杂质总量均有不同程度的增长,并产生了两个未知杂质。不同企业、不同批次的聚乙二醇6000对左乙拉西坦有关物质的影响存在差异。结论左乙拉西坦与聚乙二醇6000在高温条件下存在相容性风险,建议制剂企业优化产品处方,提高药品的质量与安全性。Objective To investigate the compatibility between antiepileptic active pharmaceutical ingredient(API)levetiracetam and binder polyethylene glycol 6000,and provide a basis for evaluating and ensuring the safety of drugs.Methods Levetiracetam and polyethylene glycol 6000 from different producers were mixed in a certain proportion,and placed under different conditions according to the test method of stability influencing factors.The compatibility of levetiracetam and polyethylene glycol 6000 was analyzed by differential scanning calorimetry and HPLC,respectively,and the thermal variations,changes of levetiracetam appearance and related substances were investigated.Results After being placed under high humidity(relative humidity of 90%)and light(4500 Lx)for 10 days,the compatibility between API and pharmaceutical excipients was proved good,while under the conditions of high temperature of 50℃and 60℃,polyethylene glycol 6000 interacted with levetiracetam,resulting in the growth of levetiracetam related substances including impurity A and total amount of impurities,along with the production of two unknown impurities.Polyethylene glycol 6000 from different producers and different batches had different effects on the related substances of levetiracetam.Conclusion There is a risk of compatibility between levetiracetam and polyethylene glycol 6000 under elevated temperatures,and it is recommended that preparation producers optimize product prescriptions and improve the quality and safety of drugs.

关 键 词：左乙拉西坦 聚乙二醇6000 相容性 

分 类 号：R943[医药卫生—药剂学]