Characterization of Polysorbate Ester Fractions and Implications in Protein Drug Product Stability

聚山梨酯 化学 胶束 肺表面活性物质 色谱法 生物制药 临界胶束浓度 水解 溶解度 有机化学 化学工程 生物化学 水溶液 遗传学 生物 工程类
作者
Anthony A. G. Tomlinson,Isidro E. Zarraga,Barthélemy Demeule
出处
期刊:Molecular Pharmaceutics [American Chemical Society]
卷期号:17 (7): 2345-2353 被引量:42
标识
DOI:10.1021/acs.molpharmaceut.0c00093
摘要

Polysorbates (PS) are commonly used surfactants in biopharmaceutical protein formulations. However, they are susceptible to a variety of degradation pathways, including chemical hydrolysis, oxidation, and enzymatic hydrolysis. Polysorbates are also heterogeneous mixtures, and it has been observed that the patterns of degradation can be strikingly different between the different pathways. Polysorbates (PS20 and PS80) were fractionated, and the fractions were characterized for their physicochemical properties, such as surface tension, micelle size, critical micelle concentration (CMC), and agitation protection for a monoclonal antibody (mAb). This report seeks to use this information to inform how these properties might change in polysorbates as they degrade in biopharmaceutical formulations. The physicochemical properties examined shed light on some of the differences between PS types and the different chemical components of polysorbates. Differences in physicochemical properties for fractionated polysorbates could help inform biopharmaceutical formulations that use PS surfactants. Importantly, they show that subspecies of PS20 are far more distinct from each other than those of PS80. Fractions of PS20 showed highly different critical micelle concentrations and effects on equilibrium surface tension. These differences, and possibly other untested parameters, led to vastly different protective effects for a model mAb under agitation stress. Additionally, the propensity of various PS fractions to form micelles can impact both polysorbate quantitation measurements, some of which rely on micellization, and the effective solubility of hydrophobic compounds (e.g., fatty acids) in the surfactant solution.
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