(89c) A Comprehensive Modeling for Predicting Oxygen-Related Degradation in Pharmaceutical Drug Product Stability

A comprehensive model integrating mass transfer and reaction kinetics of a drug product in a primary container to predict pharmaceutical drug product stability was developed. The study was focused on oxygen-induced degradation during product shelf life. Traditional accelerated stability study and analysis, although efficient in gathering data quickly, may not accurately represent the behavior of drug products during the real-life storage conditions.

Our research highlights the potential inadequacies of assumptions made by well-mixed models, particularly when the real-life environment transitions to regimes are limited by reaction kinetics. By incorporating the Damköhler number, our integrated model can effectively bridge the gap between drug product conditions used in accelerated tests and those encountered in real-life storage. Damköhler numbers are dimensionless numbers used to connect the chemical reaction timescale (reaction rate) to the mass transport rate occurring in a system.

The findings indicate that the conventional method of extrapolating kinetic constants from accelerated tests can lead to significant overestimations, especially in reaction-limited scenarios. The model, validated with experimental data, offers improved accuracy in predicting the long-term stability of drug products, surpassing the capabilities of well-mixed models. This study underscores the importance of developing reliable predictive models that account for the significant roles of diffusion and permeation under real-life storage conditions, ensuring the sustained efficacy and accuracy of pharmaceutical drug product stability throughout the shelf life.