Abstract
Background: Imipenem and meropenem are the carbapenem antibiotics most commonly used for the treatment of severe bacterial infections. Their stability behavior, which focuses on degradation products, has been continually reported. Strategies based on in silico prediction have been explored as an additional tool that provides additional information about drug stability. Methods: A comparison between experimental and predictive data, with a focus on stability and degradation products, was performed by examining the literature data and the in silico results. The experimental data were obtained from the literature throughdatabase searches. The in silico degradation prediction was performed through the software Zeneth 9.0, which strictly focused on degradation products. With a focus on stability, degraded samples of meropenem and imipenem were investigated in terms of biological safety, applying an in vitro cytotoxicity assay by MTT reduction and neutral red uptake. Results: From the literature survey, it was found that 11 major degradation products for both carbapenems mainly formed from modifications on the b-lactam ring and dimerization. By using the Zeneth software, a large number of substances were predicted, considering the probability of occurring and the selected stressors. Even in low numbers, the comparative results indicated similarity in 4 degradation products, with high probability. About cytotoxicity, the cell viability by MTT assay was significantly reduced for imipenem samples degraded during 4 hours. For meropenem, applying neutral red uptake assay, a reduction of cell viability was observed in samples stored for 4 hours. Conclusion: Drug stability assay includes different approaches, which can be used favorably from the interaction between all areas of interest, including experimental practice and predictive modelling assay.
Published Version
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