Dual Effect of Histidine on Polysorbate 20 Stability: Mechanistic Studies
| Autor: | Christian Schӧneich, Y. John Wang, Sandeep Yadav, Olivier Mozziconacci, Lin Zhang |
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| Rok vydání: | 2017 |
| Předmět: |
Hydrochloride
Chemistry Pharmaceutical Amidines Pharmaceutical Science Polysorbates 02 engineering and technology Oxidative phosphorylation Acetates Buffers 030226 pharmacology & pharmacy Mass Spectrometry Excipients 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Stability Liquid chromatography–mass spectrometry Pharmacology (medical) Histidine Pharmacology Chromatography Aqueous solution Organic Chemistry Water 021001 nanoscience & nanotechnology Oxidants Solutions chemistry Forced degradation Molecular Medicine Degradation (geology) Polysorbate 20 0210 nano-technology Oxidation-Reduction Biotechnology |
| Zdroj: | Pharmaceutical research. 35(2) |
| ISSN: | 1573-904X |
| Popis: | L-Histidine (L-His) and polysorbate 20 (PS20) are two excipients frequently included in parenteral products to stabilize biotherapeutics. The objective of the current work was to investigate the impact of L-His on PS20 stability in aqueous solutions when subjected to forced oxidation and accelerated stability testing. The stability of PS20 in L-His buffer was compared with that in acetate buffer. Forced oxidation of PS20 in these two buffer systems was initiated by a free radical generator, 2,2′-azobis (2-amidinopropane) hydrochloride (AAPH), while accelerated stability tests were carried out at 40°C. Ultra-performance liquid chromatography mass spectrometry was utilized to monitor intact PS20 and to analyze degradation products. Our results demonstrate a dual effect of L-His on PS20 stability. During exposure to AAPH, L-His protects PS20 from oxidation. Stable isotope labeling of L-His with 13C was employed for mechanistic investigations. The protection of L-His was abrogated when acetate was added to L-His buffer, implying that the anti-oxidative activity of L-His may be compromised by specific counter ions. The replacement of L-His by various His derivatives led to significant changes in the protection of PS20 against AAPH-induced degradation. In contrast to forced degradation, the addition of L-His promoted oxidative PS20 degradation during accelerated storage at 40°C in solution, generating mainly short chain POE-laurates. L-His exhibits a dual effect on the stability profile of PS20, protecting against AAPH-induced oxidation but promoting oxidative degradation during accelerated stability testing. |
| Databáze: | OpenAIRE |
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