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

Famotidine, a widely used H₂-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.