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

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Author: JIANG Yun ^1, ²  ZHOU Ying ^1, ² ZHAO Yong ^1, ² ZHENG Jinfeng ^1, ² LIU Yanming ^1, ²

Affiliation: 1. Hunan Institute for Drug Control, Changsha 410001, China 2. NMPA Key Laboratory for Pharmaceutical Excipients Engineering Technology Research, Changsha 410001, China

Keywords: Levetiracetam Polyethylene glycol 6000 Compatibility

DOI: 10.12173/j.issn.1008-049X.202311107

Reference: JIANG Yun, ZHOU Ying, ZHAO Yong, ZHENG Jinfeng, LIU Yanming.Study on the compatibility between pharmaceutical excipient polyethylene glycol 6000 and antiepileptic active pharmaceutical ingredients levetiracetam[J].Zhongguo Yaoshi Zazhi,2023,26(12): 57-65.DOI:10.12173/j.issn.1008-049X.202311107.[Article in Chinese]  Copied

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Abstract

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 (4 500 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.

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