Kinetics of human insulin degradation in the solid-state: an investigation of the effects of temperature and humidity

• Published in: Journal of pharmaceutical sciences 2024-12
• Main Authors: Fagan, A., Bateman, L.M., O'Shea, J.P., Crean, A.M.
• Format: Article
• Language: English
• Subjects: Biopharmaceutical characterisation; Chemical stability; Deamidation; Insulin; Kinetics; Physical stability; Protein aggregation; Solid-state stability; Water Sorption
• ISSN: 0022-3549; 1520-6017; 1520-6017
• DOI: 10.1016/j.xphs.2024.11.032

With the increasing development of oral peptide dosage forms, a comprehensive understanding of factors affecting peptide drug stability in the solid-state is critical. This study used human insulin, as a model peptide, to examine the individual and interactive effects of temperature and humidity on its solid-state stability. Insulin was stored at temperature (25°C, 40°C, and 6 °C) and humidity (1%, 33% and 75%) over 6 months. Primary degradation pathways were deamidation and covalent aggregation. Degradation product formation rates were determined empirically and modelled using the humidity-corrected Arrhenius equation. Temperature had a major impact on deamidation and covalent aggregation rates, with the reaction rates increasing with temperature. The effect of humidity was temperature dependent. Moisture induced degradation was minimal at 25°C and 40°C, but an important factor at 60°C. Dynamic vapour sorption analysed determined a clear differences in insulin moisture sorption characteristics at 60°C relative to 25°C and 40°C. The findings suggest that the effect of moisture on insulin deamidation and covalent aggregation rates was not a function of water content but the nature of the insulin moisture interaction.