聚山梨酯
活性成分
化学
生物制药
水解
色谱法
肺表面活性物质
山梨醇酐
剂型
成分
降级(电信)
设计质量
聚乙烯醇
有机化学
生物化学
粒径
药理学
脂肪酸
生物技术
脂肪酸
计算机科学
食品科学
物理化学
生物
电信
医学
作者
Tobias Graf,Kathrin Abstiens,Frank Wedekind,Carsten Elger,Markus Haindl,Christine Wurth,Michael Leiß
标识
DOI:10.1016/j.ejpb.2020.05.017
摘要
Hydrolysis of polysorbate in biopharmaceutical liquid formulations upon long-term storage represents a risk factor, since reduction of the intact surfactant concentration may compromise protein stability. Moreover, accumulation of polysorbate degradation products is associated with the formation of particulates potentially affecting drug product stability and quality. These effects are conventionally assessed by real-time end-of-shelf life studies constituting an integral yet lengthy process of formulation development. To accelerate this procedure, we describe here a powerful tool to conduct shake stress studies based on the controlled hydrolysis of polysorbate 20 by beads-immobilized lipases. For this purpose, the production of stable, partially degraded material characterized by a representative presence of non-emulsifying degradants such as ethoxylated sorbitan and free fatty acids was monitored by state-of-the-art chromatographic methods ensuring realistic pharmaceutical conditions. Freeze-thaw, shaking and shipping stress studies of a mAb formulation did not only demonstrate that this approach is useful to determine the critical degradation level impairing drug product quality, but furthermore revealed significant differences in protective effects depending on the hydrolysis pattern. As these results emphasize, the outlined strategy may support formulation scientists to unveil the interrelationship between polysorbate hydrolysis products and stabilization of the active pharmaceutical ingredient in a holistic and time-saving manner.
科研通智能强力驱动
Strongly Powered by AbleSci AI