Polysorbate stability : effects of packaging materials, buffers, counterions, and pH

Lebar, Blaž (author), Lekić, Tinkara (author), Košir, Pija (author), Kastelic, Miha (author), Zidar, Mitja (author), Mravljak, Janez (author), Pajk, Stane (author)

Polysorbates, widely used excipients in drug formulations, present a stability challenge due to complex degradation processes. This study investigates the hydrolysis of polysorbate (PS) under temperature stress (50 °C), focusing on the impact of primary packaging materials (glass vs. plastic vials), buffers (histidine and acetic acid), counterions (chloride vs. malate), and pH (4–7). Our findings reveal that leachables from plastic vials inhibit PS degradation in both histidine and acetic acid buffers. Kinetic parameters derived from sigmoidal fitting suggest distinct degradation mechanisms for each buffer. Furthermore, the malate counterion with histidine displays inhibitory effects on PS hydrolysis. Principal component analysis was employed to identify key factors. These results highlight the critical role of excipients and packaging in PS stability, providing valuable insights for biopharmaceutical formulation development and a deeper understanding of PS degradation complexities.

• Language: English
• Keywords: polysorbates, primary packaging material, hydrolysis, stability, histidine, acetic acid, principal component analysis
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: 8 str.
• Numbering: Vol. 665, art. 124598
• PID: 20.500.12556/RUL-162516
• UDC: 66.093+544.7
• ISSN on article: 0378-5173
• DOI: 10.1016/j.ijpharm.2024.124598
• COBISS.SI-ID: 208616195
• Publication date in RUL: 25.09.2024

Record is a part of a journal

• Title: International journal of pharmaceutics
• Shortened title: Int. j. pharm.
• Publisher: Elsevier
• ISSN: 0378-5173
• COBISS.SI-ID: 3087631

Licences

• License: CC BY-NC 4.0, Creative Commons Attribution-NonCommercial 4.0 International
• Link: http://creativecommons.org/licenses/by-nc/4.0/
• Description: A creative commons license that bans commercial use, but the users don’t have to license their derivative works on the same terms.

Secondary language

• Language: Slovenian
• Keywords: polisorbati, primarni embalažni material, stabilnost, histidin, ocetna kislina, analiza glavne komponente, farmacevtska kemija, hiroliza, površinska kemija

Projects

• Funder: Other - Other funder or multiple funders
• Funding programme: Novartis Pharmaceutical Manufacturing LLC

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P1-0208
• Name: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin