Exploring the solvent effect on crystal morphology of naphazoline hydrochloride: Molecular dynamic simulations and experiments

Abstract

The crystal morphologies of naphazoline hydrochloride (NPZ) in vacuum and binary solvent conditions (methanol + ethyl acetate, methanol + ethanol, methanol + isopropanol and 2-moxyethanol + isopropanol) were investigated by the molecular dynamic (MD) simulation and experiments. The Hirshfeld surface (HS) analysis was employed to explore the interactions in the crystal structure of NPZ, and results revealed that H···H and H···Cl/Cl···H contacts were primary contributing interactions. The attachment energy (AE) model was utilized to simulate the crystal habit of NPZ in vacuum based on the single crystal data, resulting in the identification of six morphological crystal facets. Also, the structural characteristics of dominant crystal faces were analyzed. The crystal morphologies of NPZ in different binary solvents were predicted using the modified attachment energy (MAE) model. The simulation results indicated that the solvent adsorption processes on the crystal surfaces were exothermic, and {002} face had largest morphological importance in all solvent systems. Furthermore, the experimental morphology of NPZ obtained from the methanol + ethyl acetate system was consistent with the crystal habit predicted by MAE model, which was plate-shape. On this basis, the intermolecular interactions between solvent molecules and {002} as well as {1 1––1} facets were analyzed detailly by radial distribution function (RDF) and mean square displacement (MSD), respectively. The RDF analysis indicated that N atoms of {002} face formed hydrogen bonds with O atoms of solvent molecules, resulting in an evident change in the total facet area of this face. Moreover, MSD analysis demonstrated that the absorptions of solvent molecules on the {1 1––1} face were the main factor affecting the growth rate of this crystal surface.