Particle-based investigation of excipients stability: the effect of storage conditions on moisture content and swelling†

Abstract

Moisture sensitivity poses a challenge in formulating oral dosage forms, particularly when considering disintegrants’ swelling due to prior moisture exposure, impacting performance and physical stability. This study utilises dynamic vapour sorption to simulate real-world storage scenarios, investigating the equilibrium moisture content and dynamics of eight commonly used excipients in oral solid dosage forms. A model was developed to determine the kinetic rate constant of moisture sorption and desorption for different storage conditions. Dynamic vapour sorption tests revealed that excipients with higher moisture-binding capacities showed slower equilibration to the target relative humidity (RH). Elevated temperatures accelerated the moisture sorption/desorption process for all excipients, reducing the equilibrated moisture content for most, except mannitol and lactose. Particle imaging over a 14-day accelerated storage period quantified swelling, indicating approximately 6% increase in particle diameter for croscarmellose sodium (CCS) and sodium starch glycolate (SSG), and a lesser 2.7% for microcrystalline cellulose (MCC), predominantly caused by the humidity. All excipients reached their swelling peak within the first day of storage, with permanent particle size enlargement for CCS and SSG, whereas MCC displayed a partial reversibility post-storage. Enhancing our understanding of excipients’ stability and interaction with moisture and the resulting particle swelling contributes to the rational design of oral solid dosage formulations and promotes a better understanding of their long-term physical stability.