Crystal Morphology Modeling of Solvates and Hydrates of Organic Molecular Crystals: Olanzapine Solvate and Dihydrate

Crystal morphology modeling of organic molecular solvates and hydrates remains largely unexplored due to the complex intermolecular interactions and growth units involved in the attachment at surface sites. In this paper, we present a mechanistic model to predict the crystal morphology of olanzapine-methanol solvate and olanzapine dihydrate. This study provides mechanistic insight into predicting the crystal habits of solvates and hydrates for broader classes of organic molecules. In this model, we assume that olanzapine incorporated into the solid state as a cluster consists of a solute together with a stoichiometric number of solvent molecules. Binding energy calculations are used to identify the most probable growth unit clusters, which is an olanzapine-methanol tetramer for the methanol solvate crystal, and olanzapine-water hexamer for the dihydrate crystal. The close agreement between the experimentally observed and the predicted morphologies lends support to the utility of the model.

Automated summary

Crystal morphology modeling of organic molecular solvates and hydrates is largely unexplored due to complex intermolecular interactions and growth units. A mechanistic model was presented to predict the crystal morphology of olanzapine-methanol solvate and olanzapine dihydrate, with binding energy calculations identifying the most probable growth unit clusters. The close agreement between experimentally observed and predicted morphologies supports the utility of the model.