(606b) Solvent Effect On Crystal Morphology: A Hybrid Approach of a Mechanistic Model and Molecular Dynamics

The control of crystal morphology during crystallization processes has a great impact on the end-use properties of the materials (e.g., optical properties) and the downstream performance of the manufacturing process such as the separation characteristics. The crystal morphology depends on external factors such as solvent, supersaturation, temperature, additives and impurities. Various theoretical and computational approaches have been carried out to understand the relation between controlling the crystal morphology and the external growth factors.

Recently, a realistic crystal growth model was developed for non-centrosymmetric solute molecules[1] based on the spiral growth model proposed by Burton, Cabrera and Frank (BCF). This model well explained the non-isotropic behavior of complex drug molecules to predict the crystal shape. In solution growth, the interfacial energies between the solute and the solvent are applied to the spiral growth model. However, the interfacial energies are calculated at the macroscopic scale, so it is hard to relate the microscopic behavior of the interface between the solute and the solvent such as the free energy barriers of the solute molecules that control the rate of incorporation of solute into kink sites.

Molecular simulations have been used to understand the interfacial interactions between solute and solvent molecules at an atomistic level[2] . We applied the atomistic information from the molecular simulations into the mechanistic model of the crystal growth to consider the detailed solvent effect for organic molecules of realistic complexity such as active pharmaceutical ingredients (APIs).

[1] Kuvadia, Z. B.; Doherty, M. F. Spiral growth model for faceted crystals of non-centrosymmetric organic molecules grown from solution. Crystal Growth & Design 2011, 11, 2780

[2] Piana, S.;Gale, J. D. Understanding the barriers to crystal growth: Dynamical simulation of the dissolution and growth of urea from aqueous solution. Journal of the American Chemical Society 2005, 127, 1975