Impact of peroxide content in excipients and antioxidants on famotidine oxidative stability

Gabrič, Alen (author), Hodnik, Žiga (author), Ilaš, Janez (author), Pajk, Stane (author)

Famotidine, a widely used H$_2$-receptor antagonist, exhibits sensitivity to oxidative degradation, particularly in the presence of excipients containing peroxide impurities. This study explores the oxidative stability of famotidine under various storage conditions, with a specific focus on excipients with varying peroxide contents. A stability-indicating liquid chromatography-mass spectrometry (LC-MS) method was developed to identify and quantify famotidine degradation products, providing detailed insights into oxidative pathways. In addition, Zeneth software was employed to predict potential degradation products, and its predictive accuracy was evaluated against experimental findings. Antioxidants, including ascorbic acid, propyl gallate, and ethylenediaminetetraacetic acid (EDTA), were incorporated into compressed compatibility mixtures to assess their effects on peroxide-mediated degradation. While propyl gallate and EDTA consistently reduced peroxide levels and enhanced stability, ascorbic acid unexpectedly acted as a pro-oxidant under stress conditions, accelerating peroxide formation in povidone. These findings provide critical insights into mitigating oxidative degradation in famotidine and other solid dosage forms, emphasizing the importance of selecting appropriate excipients, antioxidants, and predictive tools to ensure product stability.

• Language: English
• Keywords: peroxides, hydrogen peroxide, famotidine, chemical compounds, Zeneth software
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: Str. 259-272
• Numbering: Vol. 75, iss. 2
• PID: 20.500.12556/RUL-175770
• UDC: 543.2/.9:615.4:54
• ISSN on article: 1846-9558
• DOI: 10.2478/acph-2025-0020
• COBISS.SI-ID: 255015171

Copyright

Podatek o licenci CC BY-NC-ND 4.0 je naveden na pristajalni strani članka (glej zgoraj izvorni URL). (Datum opombe: 7. 11. 2025)

• Publication date in RUL: 07.11.2025

Record is a part of a journal

• Title: Acta pharmaceutica
• Shortened title: Acta pharm.
• Publisher: Croatian Pharmaceutical Society
• ISSN: 1846-9558
• COBISS.SI-ID: 3817585

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: peroksidi, vodikov peroksid, famotidin, kemične spojine, programska oprema Zeneth, farmacevtska kemija, oksidacija, peroksidi

Projects

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

• Funder: Krka d.d.