Solvent Dynamics and Thermodynamics at the Crystal–Solution Interface of Ibuprofen

The choice of solvent is key in the manufacturing of solution-grown crystals due to the critical effect it can exert on their morphology. Here we set out to investigate the dynamics and thermodynamics of solvent molecules at the crystal–solution interface for the morphologically dominant crystal faces of ibuprofen. In particular, we evaluate how thermodynamically favorable the desorption of a solvent molecule is and estimate the rate of exchange of adsorbed solvent molecules with molecules from the bulk solution. This analysis is carried out for all four morphologically dominant crystal faces of ibuprofen, {100}, {002}, {011}, and {110}, and ten solvents, i.e. water, 1-butanol, toluene, cyclohexanone, cyclohexane, acetonitrile, trichloromethane, methanol, ethyl acetate, and ethanol. Our work reveals that the structure of the solution and the exchange dynamics can be strongly dependent on both the crystal face and the solvent: i.e., the same solvent can show radically different structure when it is in contact with different faces and alternatively the same face can induce different structuring in different solvents. Moreover, we find particularly strong surface–solvent interactions for the {002} and {100} crystal faces in several of the solvents examined. We conclude that the role of desolvation in the growth process is solvent- and face-specific, and therefore it has the potential of affecting the crystal shape anisotropy. We provide a framework to rationalize this effect on the basis of molecular simulations of the crystal/solution interface.