Analytical Sciences, WuXi Biologics, 1951 Huifeng West Road, Fengxian District, Shanghai, 201400, China.
Analytical Sciences, WuXi Biologics, 1951 Huifeng West Road, Fengxian District, Shanghai, 201400, China.
J Pharm Biomed Anal. 2023 Sep 5;233:115496. doi: 10.1016/j.jpba.2023.115496. Epub 2023 May 30.
A study on the polysorbate 80 stability in various formulation buffers commonly used in biopharmaceuticals was performed, to investigate the excipients influence on polysorbate 80 degradation. Polysorbate 80 is a common excipient in biopharmaceutical products. However, its degradation will potentially impact the drug product quality, and may trigger protein aggregation and particles formation. Due to the heterogeneity of the polysorbates and the mutual effects with other formulation compositions, the study of polysorbate degradation is challenging. Herein, a real-time stability study was designed and performed. The polysorbate 80 degradation trend was monitored by fluorescence micelle-based assay (FMA), reversed-phase-ultra-performance liquid chromatography-evaporative light scattering detector (RP-UPLC-ELSD) assay, and LC-MS assay. These assays provide orthogonal results to reveal both the micelle-forming capability and the compositional changes of polysorbate 80 in different buffer systems. The degradation occurred after a period of storage under 25 °C in different trend, which indicates the excipients could impact the degradation kinetics. Upon comparison, the degradation is prone to happen in histidine buffer than in acetate, phosphate or citrate buffers. LC-MS confirms oxidation as an independent degradation pathway with detection of the oxidative aldehyde. Thus, it is necessary to pay more attention to the excipients selection and their potential impact on polysorbate 80 stability to achieve longer shelf life for the biopharmaceuticals. Besides, the protective roles of several additives were figured out, which could be applied as potential industrial solutions to the polysorbate 80 degradation issues.
本研究考察了辅料对聚山梨酯 80 降解的影响，对生物制药中常用的各种制剂缓冲液中的聚山梨酯 80 稳定性进行了研究。聚山梨酯 80 是生物制药产品中的常用辅料。然而，其降解可能会影响药物产品质量，并可能引发蛋白质聚集和颗粒形成。由于聚山梨酯的不均一性及其与其他制剂成分的相互作用，对聚山梨酯降解的研究具有挑战性。在此，设计并进行了实时稳定性研究。通过基于荧光胶束的测定法（FMA）、反相超高效液相色谱-蒸发光散射检测器（RP-UPLC-ELSD）测定法和 LC-MS 测定法监测聚山梨酯 80 的降解趋势。这些测定法提供了正交结果，揭示了不同缓冲体系中聚山梨酯 80 的胶束形成能力和组成变化。在 25°C 下储存一段时间后，降解以不同的趋势发生，这表明辅料会影响降解动力学。相比之下，在组氨酸缓冲液中比在乙酸盐、磷酸盐或柠檬酸盐缓冲液中更容易发生降解。LC-MS 证实氧化是一种独立的降解途径，并检测到氧化醛。因此，有必要更加注意辅料的选择及其对聚山梨酯 80 稳定性的潜在影响，以实现生物制药更长的货架寿命。此外，还确定了几种添加剂的保护作用，这些添加剂可以作为潜在的工业解决方案应用于聚山梨酯 80 降解问题。
