Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS 66047.
Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS 66047.
J Pharm Sci. 2022 Sep;111(9):2435-2444. doi: 10.1016/j.xphs.2022.06.011. Epub 2022 Jun 16.
Polysorbate is a key excipient included in formulations of therapeutic proteins to help prevent aggregation and surface adsorption. The stability of both polysorbate and therapeutic proteins can be compromised by oxidative degradation. In general, polysorbate is added to formulations at concentrations above the critical micelle concentration (cmc). To date, however, few experiments have quantitatively addressed the extent of extra- and intra-micellar oxidation of polysorbate in pharmaceutically relevant buffers. This study utilizes 2,2'-azobis(2-methylpropionamidine)dihydrochloride (AAPH), a peroxyl radical-generating initiator, C11-BODIPY(581/591), a lipid peroxidation probe, and fluorescence spectroscopy to reveal that both intra- and extra-micellar oxidation proceed in pharmaceutically relevant phosphate and histidine buffers. It is further demonstrated that the relative extent of oxidation observed in the intra- and extra-micellar compartments is similar irrespective of the buffer system.
聚山梨酯是治疗性蛋白制剂中包含的关键辅料，有助于防止聚集和表面吸附。聚山梨酯和治疗性蛋白的稳定性都可能因氧化降解而受到影响。通常，聚山梨酯以高于临界胶束浓度（cmc）的浓度添加到制剂中。然而，迄今为止，很少有实验定量研究了聚山梨酯在药学相关缓冲液中胶束内外氧化的程度。本研究利用 2,2'-偶氮双（2-甲基丙脒）二盐酸盐（AAPH），一种过氧自由基引发剂，C11-BODIPY（581/591），一种脂质过氧化探针和荧光光谱法，揭示了胶束内外的氧化都在药学相关的磷酸盐和组氨酸缓冲液中进行。进一步证明，无论缓冲体系如何，在胶束内外隔室中观察到的氧化程度的相对程度是相似的。
