Crystal growth and morphology of molecular crystals

Organic molecular crystals are often the main active ingredient in pharmaceutical drug products. The crystal morphology of these materials plays a significant role in their ease of separation from the mother solution phase, physical behaviour during downstream unit processes and their dissolution profiles and delivery of the active ingredient to the patient. Molecular modelling can be used to predict crystal morphologies, in terms of the strengths of their internal intermolecular interactions and their external crystallisation environment, hence providing a guide to the experimental conditions required to produce a pre-defined crystal morphology. Here, the use of calculations of intermolecular interaction strength, nature and directionality in the prediction and analysis of morphologies is reviewed. These calculations are in terms of the intermolecular interactions within the crystal structure, along with the solute/solvent interactions at the crystal/solution interface, to predict an equilibrium morphology and habit modification that can be governed by the crystallisation solvent.