Atomistic Simulation To Understand Anisotropic Growth Behavior of Naproxen Crystal in the Presence of Polymeric Additives

Polymeric additives can either inhibit or promote the growth of a crystal. While crystal growth inhibition by additives/​impurities has been widely documented, the molecular-level mechanisms by which additives promote crystal growth are largely elusive. In this study, we use molecular dynamics simulations to model the interactions among a polymeric additive (polyvinylpyrrolidone), solute (naproxen), and solvent (ethanol/​water mixture) molecules occurring at the crystal/​solution interface. At the (01̅1) surface, solvent interactions with the crystal surface and solute molecules are diminished in the presence of the additive, thereby lowering the solvation barrier to crystal growth. Besides, the interaction of solute molecules with this surface is enhanced, leading to crystal growth promotion along the −b axis. On the contrary, the additive preferentially interacts with the (011) face and the solute–solvent interaction is stronger at this crystal face. These two factors lower the adsorption rate of solute molecules onto this face and consequently retard crystal growth along the +b direction. Further, in the presence of the additive, mobility of the solute is slowed down at the (01̅1) face (supports the promotion event); in contrast, at the (011) face, the solute exhibits a larger mobility (supports the inhibition event). The simulation results, while providing insights into the anisotropic growth behavior of naproxen crystals in the presence of polymeric additives, have implications on the selection of additives for crystallization inhibition in pharmaceutical and agrochemical formulations, as well as for modulation of undesired crystal shapes to enable better downstream processing.