Effect of microcrystalline cellulose properties on the stability of moisture-sensitive formulations

The stability of moisture-sensitive active pharmaceutical ingredients (APIs) in solid dosage forms is a critical factor for product quality and shelf-life. Excipient selection plays a key role in preventing moisture-induced degradation pathways. To assess the influence of excipients on API instability, an excipient compatibility study was conducted using several commonly used excipients. Among these, microcrystalline cellulose (MCC) induced more degradation of acetylsalicylic acid (moisture-sensitive model API) and was therefore selected for further investigation. Two MCC grades, distinguished by their high and low initial moisture content, were examined to determine the effect of MCC type and excipient ratio on API stability. These factors were systematically assessed across six tablet prototypes using the Accelerated Predictive Stability (ASAP) approach. Storage across several temperature and humidity conditions demonstrated that a higher MCC content resulted in higher water content and instability of the model API, whereas tablet prototypes with lower MCC content showed improved stability. Arrhenius-based modelling generated robust fits (R2 >0.9, Q2 >0.7) and confirmed humidity as a dominant driver of degradation, with MCC grades playing a secondary role. Model predictions were validated by real-time stability studies at 25°C/60%RH and 40°C/75%RH over six months, with measured and predicted degradation differing less than 1%. The findings underscore the critical role of excipient selection and water content in stabilizing moisture-sensitive APIs and demonstrate the value of predictive modelling for formulation development and risk assessment. Integrating predictive stability modelling can accelerate shelf-life estimation and guide excipient selection, offering a robust tool for developing stable pharmaceutical products.