Zhuan Cheng , Pengzhen Wang , Luting Liu, Quanmin Chen, Jeremy Guo
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引用次数: 0
Abstract
Polysorbate 80 (PS80) is a non-ionic surfactant extensively utilized in biopharmaceutical formulations for stabilizing proteins. However, PS80 degradation has become a widespread concern throughout the industry over the past decade. In this work, the impact of most frequently employed pH/buffer systems on the stability of PS80 was assessed. PS80 degraded fastest in histidine buffer, followed by acetate and succinate buffers, whereas it remained stable in citrate, phosphate and tris buffers. When there was PS80 degradation, the extent of degradation was found to be pH-dependent. The predominant degradation pathway was oxidation mainly triggered by metal ions. The varying stability of PS80 across different pH/buffer systems was attributed to the role of buffer agents, which can either promote or inhibit the oxidation process through their interactions with metal ions. Specifically, buffers except histidine exhibited metal ion chelation similar to ethylenediaminetetraacetic acid (EDTA), which can suppress the oxidation of PS80, although the effectiveness of chelation varies to different extents. Furthermore, the binding capacity appeared stronger at higher pH in acetate and succinate buffers. Conversely, histidine was reported to form pro-oxidant complexes with metal ions to accelerate PS80 degradation, especially at higher pH levels. Our work for the first time offers a comprehensive understanding of PS80 oxidation in biopharmaceutical buffer systems. This provides a strong foundation for buffer and excipient selection in parenteral formulations.
期刊介绍:
The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics.
Topics covered include for example:
Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids)
Aspects of manufacturing process design
Biomedical aspects of drug product design
Strategies and formulations for controlled drug transport across biological barriers
Physicochemical aspects of drug product development
Novel excipients for drug product design
Drug delivery and controlled release systems for systemic and local applications
Nanomaterials for therapeutic and diagnostic purposes
Advanced therapy medicinal products
Medical devices supporting a distinct pharmacological effect.