Kozuch Benedykt, Weber Johanna, Buske Julia, Mäder Karsten, Garidel Patrick, Diederichs Tim
PDB-TIP, Innovation Unit, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Straße 65, 88397 Biberach an der Riss, Germany.
Institute of Pharmacy, Faculty of Biosciences, Martin-Luther-University Halle-Wittenberg, Wolfgang-Langenbeck-Strasse 4, 06120 Halle, Germany.
Pharmaceutics. 2023 Sep 16;15(9):2332. doi: 10.3390/pharmaceutics15092332.
The surfactants polysorbate 20 (PS20) and polysorbate 80 (PS80) are utilized to stabilize protein drugs. However, concerns have been raised regarding the degradation of PSs in biologics and the potential impact on product quality. Oxidation has been identified as a prevalent degradation mechanism under pharmaceutically relevant conditions. So far, a systematic stability comparison of both PSs under pharmaceutically relevant conditions has not been conducted and little is known about the dependence of oxidation on PS concentration. Here, we conducted a comparative stability study to investigate (i) the different oxidative degradation propensities between PS20 and PS80 and (ii) the impact of PS concentration on oxidative degradation. PS20 and PS80 in concentrations ranging from 0.1 mg⋅mL to raw material were stored at 5, 25, and 40 °C for 48 weeks in acetate buffer pH 5.5 and water, respectively. We observed a temperature-dependent oxidative degradation of the PSs with strong (40 °C), moderate (25 °C), and weak/no degradation (5 °C). Especially at elevated temperatures such as 40 °C, fast oxidative PS degradation processes were detected. In this case study, a stronger degradation and earlier onset of oxidation was observed for PS80 in comparison to PS20, detected via the fluorescence micelle assay. Additionally, degradation was found to be strongly dependent on PS concentration, with significantly less oxidative processes at higher PS concentrations. Iron impurities, oxygen in the vial headspaces, and the pH values of the formulations were identified as the main contributing factors to accelerate PS oxidation.
表面活性剂聚山梨醇酯20（PS20）和聚山梨醇酯80（PS80）被用于稳定蛋白质药物。然而，人们对生物制品中PSs的降解及其对产品质量的潜在影响表示担忧。氧化已被确定为在药学相关条件下普遍存在的降解机制。到目前为止，尚未在药学相关条件下对两种PSs进行系统的稳定性比较，而且对于氧化对PS浓度的依赖性知之甚少。在此，我们进行了一项比较稳定性研究，以调查（i）PS20和PS80之间不同的氧化降解倾向，以及（ii）PS浓度对氧化降解的影响。将浓度范围为0.1 mg⋅mL至原料的PS20和PS80分别在pH 5.5的醋酸盐缓冲液和水中于5、25和40 °C储存48周。我们观察到PSs的氧化降解具有温度依赖性，在40 °C时强烈降解，25 °C时中度降解，5 °C时弱降解/无降解。特别是在40 °C等高温下，检测到了快速的PS氧化降解过程。在本案例研究中，通过荧光胶束测定法检测到，与PS20相比，PS80的降解更强且氧化起始更早。此外，发现降解强烈依赖于PS浓度，在较高PS浓度下氧化过程明显较少。铁杂质、瓶顶空间中的氧气以及制剂的pH值被确定为加速PS氧化的主要因素。
