(141f) Spiral Growth Model for Organic Crystals of Real Complexity: How to Account for Non-Isotropic Behavior

Crystal morphology is known to significantly influence the end-use efficacy of solid products as well as the downstream performance of the entire process. Development of accurate, fast, first-principles-based models for prediction of crystal morphology of organic compounds is of paramount value for many industries including pharmaceutical and non-linear optical (NLO) technologies. It is well established by experiments and simulations that, at low supersaturations, crystals of organic molecules grow via spirals emanating from screw dislocations. The spiral growth model of Burton, Cabrera and Frank (1951), widely recognized as the BCF model, was developed nearly six decades ago, and several modifications exist, including the spiral growth model by Snyder and Doherty (2009). However, its implementation has been successfully demonstrated only for organic molecules or a crystal growth unit having a center of symmetry (defined as centrosymmetric). A huge majority of molecules of realistic complexity are non- centrosymmetric, and they warrant a much more rigorous treatment of the spiral growth model to give accurate crystal shape prediction. This work describes the challenges that need to be overcome to predict crystal morphology for these complex molecules and steps to meet those challenges. A detailed demonstration on how to specifically account for non-isotropic behavior in terms of kink rates is also provided. Specific cases of acetaminophen and lovastatin are discussed and the predicted crystal shapes compare favorably to experimental shapes published in literature.

References

Burton,W.K., Cabrera, N. & Frank, F.C. 1951. The growth of crystals and the equilibrium structure of their surfaces. Phil. Trans. R. Soc. A 243, 299-358

Snyder, R. C. & Doherty, M. F. 2009. Predicting crystal growth by spiral motion. Proceedings of the Royal Society A: Mathematical, Physical and Engineering Science 465, 1145-1171