Mechanistic Study on Interface Interactions and Its Effect on Crystal Growth─A Case of Cloxacillin Sodium Monohydrate

Solvents are essential factors in influencing the morphology of substances that crystallize from the solution. In this study, a combined approach involving molecular dynamics simulations and experimental investigations was employed to investigate the impact of various solvent systems on the crystal morphology of cloxacillin sodium monohydrate. The crystal morphology of cloxacillin sodium monohydrate was predicated using the modified attachment energy model, and it was verified by experiments within seven binary solvent systems (methanol + butyl acetate, methanol + acetone, methanol + acetonitrile, methanol + isopropyl alcohol, water + acetone, water + acetonitrile, and water + isopropanol). Furthermore, a strong correlation between the binding energies of solvents with the (1 0 1) and (0 1 1) crystal planes and their respective growth rates was revealed. Structural analyses of the three principal crystal faces revealed that the roughness and electrostatic potential (ESP) distribution of the crystal planes can affect the interactions between the crystal planes and solvents to varying degrees. Strong interactions between the solvent and crystal planes promoted solvent adsorption, impeding the adsorption of solute molecules and thus reducing the growth rate of the crystal planes. Additionally, radial distribution function analysis further verified the interactions between solvents and crystal planes, indicating that these interactions were primarily governed by van der Waals forces and Coulombic forces.