Factors Influencing Polysorbate's Sensitivity Against Enzymatic Hydrolysis and Oxidative Degradation |
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Authors: | Wendelin Kranz Klaus Wuchner Eleonora Corradini Michelle Berger Andrea Hawe |
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Affiliation: | 1. Coriolis Pharma Research, Fraunhoferstr 18b, 82152 Martinsried, Germany;2. Janssen Research and Development, DPD&S Biotherapeutics Development, Hochstrasse 201, 8205 Schaffhausen, Switzerland |
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Abstract: | 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. |
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Keywords: | HPLC (high-performance/pressure liquid chromatography) surfactant(s) excipient(s) protein formulation(s) stability oxidation(s) degradation product(s) hydrolysis injectable(s) analytical chemistry ACN acetonitrile AAPH 2,2′-azobis (2-amidinopropane) hydrochloride ChP Chinese Pharmacopoeia EDTA ethylenediaminetetraacetic acid FA formic acid iron at oxidation state 2+ hydrogen peroxide IPA isopropanol JP Japanese Pharmacopoeia LC-CAD liquid chromatography-charge aerosol detection LC-MS liquid chromatography–mass spectrometry ammonium hydroxide PEG polyethylene glycol POE polyoxyethylene glycol Ph. Eur. European Pharmacopoeia PS polysorbate PS20-AL polysorbate 20 all-laurate PS20-MC polysorbate 20 multicompendial PS80-AO polysorbate 80 all-oleate PS80-MC polysorbate 80 multicompendial ROS radical oxygen species USP United States Pharmacopoeia |
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