Coriolis Pharma Research, Fraunhoferstr 18b, 82152 Martinsried, Germany.
Janssen Research and Development, DPD&S Biotherapeutics Development, Hochstrasse 201, 8205 Schaffhausen, Switzerland.
J Pharm Sci. 2019 Jun;108(6):2022-2032. doi: 10.1016/j.xphs.2019.01.006. Epub 2019 Jan 11.
The aim was to compare the sensitivity of different grades of polysorbate 20 (PS20) and polysorbate 80 (PS80) against enzymatic hydrolysis and oxidative degradation in pharmaceutically relevant buffer systems. For this purpose, a fast liquid chromatography charged aerosol detection method was developed which allows to (1) differentiate between hydrolytic and oxidative PS degradation and (2) to monitor the PS decay over time. Systematic enzymatic and oxidative forced degradation studies were conducted with multicompendial PS20 and PS80, as well as all-laurate PS20 and all-oleate PS80 (with >98% oleic acid, as required by the Chinese Pharmacopoiea since 2015). No differences in the sensitivity toward enzymatic degradation were observed between multicompendial PS and high purity grade PS. However, all-laurate PS20 and all-oleate PS80 have a higher predisposition for oxidative degradation as compared to multicompendial PS20 and PS80. The buffer system used within the study played thereby a key role: histidine showed a protective effect against hydrogen peroxide-induced oxidation, whereas hydrogen peroxide oxidation of PS in acetate buffer was severe under the experimental conditions. Furthermore, ethylenediaminetetraacetic acid protected PS20 and PS80 against oxidative degradation in histidine buffer.
目的是比较不同等级的聚山梨酯 20（PS20）和聚山梨酯 80（PS80）在药物相关缓冲体系中对酶解和氧化降解的敏感性。为此，开发了一种快速液相色谱荷电气溶胶检测法，该方法允许（1）区分水解和氧化 PS 降解，（2）监测 PS 在一段时间内的衰减。系统地进行了酶促和氧化强制降解研究，使用多药典 PS20 和 PS80 以及全月桂酸 PS20 和全油酸 PS80（自 2015 年以来，中国药典要求油酸含量>98%）。在酶促降解的敏感性方面，多药典 PS 和高纯度等级 PS 之间没有差异。然而，与多药典 PS20 和 PS80 相比，全月桂酸 PS20 和全油酸 PS80 更倾向于氧化降解。因此，研究中使用的缓冲体系起着关键作用：组氨酸对过氧化氢诱导的氧化具有保护作用，而在实验条件下，乙酸盐缓冲液中的 PS 过氧化氢氧化非常严重。此外，乙二胺四乙酸可保护 PS20 和 PS80 在组氨酸缓冲液中免受氧化降解。
