Crystal Morphology Prediction of Olanzapine Forms III and IV

Abstract

It is of great significance to explore and predict crystal growth behavior that can target the optimal growth conditions and obtain ideal properties. The ability to effectively treat schizophrenia and other psychoses has led to numerous studies of olanzapine (OZPN) polymorphs. There are four reported anhydrous forms of OZPN, but two of whose crystal morphologies (forms III and IV) are still unavailable in the laboratory. Based on the advanced spiral growth model, this study predicts the crystal morphologies of OZPN forms III and IV from vapor and different solvents (i.e., water, ethyl acetate, ethanol, cyclohexane, and dichloromethane), where the potential energies between dimeric growth units (stronger than specific energy cutoff) are considered as strong bond. It is demonstrated that the growth rate of form III increases with the increase of supersaturation from 1.01 to 1.07. Form III crystallizes from solvents with the block‐like shape, whereas form IV grows with the rectangular shape, that obviously differs from the flat‐square shapes of form I and form II. This mechanistic model is able to apply on various compounds, especially for the crystals with non‐centrosymmetric molecules to obtain important guidance for their experimental preparations.