Predicting Simultaneous Water-Sorption and Crystallization Kinetics in Amorphous Solid Dispersions

In this work the physical stability was investigated by measuring and modeling the simultaneous water-sorption and API crystallization kinetics in ASDs out of nifedipine and celecoxib as APIs and poly(vinylpyrrolidone-co-vinyl acetate) and hydroxypropyl methyl-cellulose acetate succinate as polymers at various storage conditions. A new modeling approach was established to combine the water-sorption and API crystallization kinetics and thus the simultaneous kinetics in ASDs were described, understood and predicted. The driving forces for crystallization and water sorption were calculated using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT). The viscosity of wet ASDs as an indicator of the molecular mobility in the ASD was determined from viscosity measurements and modeling. The proposed approach considers the temporal change of all relevant physical quantities during storage, i.e., supersaturation and viscosity of the wet ASD. The measuring and modeling of long-term stability over two years and short-term kinetics over hours provides an understanding of API crystallization in wet ASDs and can thus be used to identify best-suited polymers, drug loads and storage conditions for ASDs.