Simultaneous Water Sorption and Crystallization in ASDs 2: Modeling Long-Term Stabilities.

The physical stability of amorphous solid dispersions (ASDs) is a major topic in the formulation research of oral dosage forms. To minimize the effort of investigating the long-term stability using cost- and time-consuming experiments, we developed a thermodynamic and kinetic modeling framework to predict and understand the crystallization kinetics of ASDs during long-term storage below the glass transition. Since crystallization of the active phrarmaceutical ingredients (APIs) in ASDs largely depends on the amount of water absorbed by the ASDs, water-sorption kinetics and API-crystallization kinetics were considered simultaneously.

Water Sorption in Rubbery and Glassy Polymers, Nifedipine, and Their ASDs.

Polymers like poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA) or hydroxypropyl methylcellulose acetate succinate (HPMCAS) are commonly used as a matrix for amorphous solid dispersions (ASDs) to enhance the bioavailability of the active pharmaceutical ingredients (APIs). The stability of ASDs is strongly influenced by the water sorption in the ASD from the surrounding air. In this work, the water sorption in the neat polymers PVPVA and HPMCAS, in the neat API nifedipine (NIF), and in their ASDs of different drug loads was measured above and below the glass-transition temperature.