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CC BY 4.0 · Pharmaceutical Fronts 2022; 04(02): e78-e88
DOI: 10.1055/s-0042-1750043
Original Article

Effect of Oxygen and Water on the Stability of Imipenem and Cilastatin Sodium for Injection

Meng Zhang
1   College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, People's Republic of China
,
Chun-Feng Liu
2   Pharmaceutical Process Optimization and Industrialization Engineering Research Center, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Xiao-Yan Chen
3   China National Medicines Guorui Pharmaceutical Co., Ltd., Huainan, People's Republic of China
,
Li-Na Yang
2   Pharmaceutical Process Optimization and Industrialization Engineering Research Center, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Chun-Mei Zhu
2   Pharmaceutical Process Optimization and Industrialization Engineering Research Center, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Jian-Hao Teng
2   Pharmaceutical Process Optimization and Industrialization Engineering Research Center, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Hao-Xiang Wu
2   Pharmaceutical Process Optimization and Industrialization Engineering Research Center, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Fu-Li Zhang
1   College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, People's Republic of China
2   Pharmaceutical Process Optimization and Industrialization Engineering Research Center, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
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Abstract

The study aimed to investigate the factors affecting the stability of imipenem and cilastatin sodium for injection (IMI/CIL) to improve the quality and stability in IMI/CIL preparation. In this study, the effects of headspace oxygen (HO), water content, particle shape, and particle size on the stability of IMI/CIL were investigated. IMI/CIL was purged with air, premixed oxygen/nitrogen gas (5%/95%), or high-purity nitrogen (99.999%) at 20, 5, or 2% oxygen levels to prepare IMI/CIL with different HO levels. IMI/CIL was stored at 30, 45, and 75% relative humidity for 30 days to prepare IMI/CIL with different water contents. High-performance liquid chromatography method was used for analysis. The results showed that oxygen, water, particle shape, and particle size had significant effects on the stability of IMI/CIL, and free water content is a better predictor of the safety and stability of imipenem and cilastatin sodium than the total water content. The optimization scheme of the above parameters is proposed, which significantly improves the stability of IMI/CIL. This study led to a better understanding of the degradation mechanism of imipenem and cilastatin sodium, and could provide a reference for the selection and control of IMI/CIL process conditions. This study would contribute to the development of IMI/CIL with improved stability.

Keywords

imipenem - cilastatin sodium - stability - oxidation - free water


Publication History

Article published online:
04 July 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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