Unveiling the Amphotericin B Degradation Pathway and Its Kinetics in Lipid-Based Solutions
Autor: | Éverton N. Alencar, Phawanan Sawangchan, Lee E. Kirsch, Eryvaldo Sócrates T. Egito |
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Rok vydání: | 2021 |
Předmět: |
Antifungal Agents
animal diseases Kinetics Pharmaceutical Science 02 engineering and technology 030226 pharmacology & pharmacy High-performance liquid chromatography 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Reaction rate constant Adsorption Amphotericin B parasitic diseases Chromatography Autoxidation urogenital system technology industry and agriculture bacterial infections and mycoses 021001 nanoscience & nanotechnology Lipids Solvent chemistry Degradation (geology) Methanol 0210 nano-technology Oils |
Zdroj: | Journal of Pharmaceutical Sciences. 110:1248-1258 |
ISSN: | 0022-3549 |
DOI: | 10.1016/j.xphs.2020.11.004 |
Popis: | The purpose of this work was to determine the degradation pathway of Amphotericin B (AmB) and its kinetics in lipid-based solutions. Mixtures of AmB in lipophilic solvent media were stored under different conditions, such as surface area, temperature, light exposure, presence of antioxidants and other co-solutes. AmB was quantified by HPLC and UV–Vis spectrometry. Empirical models were proposed, and degradation rate constants were estimated by nonlinear regression. The HPLC method was precise and accurate with linearity from 4.45 to 52.0 nM. Surface area studies revealed that adsorption to glass did not affect AmB loss. Unsaturated oils and methanol better preserved AmB compared to medium chain-triglyceride. Temperature increased AmB loss in a nonlinear behavior and the presence of antioxidants reduced its degradation. Under dark conditions, autoxidation was the predominant degradation pathway of AmB in oil, which undergoes a complex degradation. Under light exposure, photo-oxidation accounted for AmB loss, which appeared to be of pseudo-first order. AmB oily samples should be preferably stored in glass vials protected from light with the addition of antioxidants. Furthermore, this work encourages further investigation in other media for future complex modeling and estimation of AmB degradation and kinetics in lipid-based formulations. |
Databáze: | OpenAIRE |
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