Polymer effects on crystallization at the amorphous atazanavir-water interface

Abstract Amorphous solid dispersions are a highly relevant pharmaceutical formulation strategy increasingly employed to enhance the dissolution performance of drugs with poor aqueous solubility. Formulation additives are known to play an important role in the phase behavior of such pharmaceutical products, as they can potentially promote or inhibit solid-state crystallization of drug molecules in the dispersion matrix as well as crystallization from supersaturated solutions. Considerably less is known about the potential role of dissolved additives on the fate of amorphous drug-rich interfaces which can arise due to liquid–liquid phase separation during dosing. In this study, amorphous drug films are crystallized in buffer containing various polymeric formulation additives and analyzed via atomic force and scanning electron microscopy methods to explore the effect of additives on the evolution of surface crystals. A 2D lattice Monte Carlo model further examines the polymer systems to determine important modes of polymer action. Results demonstrate adsorbed polymer competitively inhibits crystal growth by preferential interaction with high energy sites.