The Institute of Pharmaceutical Innovation

Computer simulation of crystallization from solution

Computer simulation of crystallization from solution

J. Anwar* & P.K. Boateng

The early stages of crystallization are not fully understood, a particularly challenging problem being crystallization from solution. The processes involved at an atomic level remain elusive to experiment. Furthermore, crystallization from solution has been thought to be inaccessible by atomistic computer simulations. This study demonstrates that crystallization from solution can in fact be simulated using the method of molecular dynamics for a model solute/solvent system consisting of atomic species characterized by the Lennard-Jones potential function. The model has been applied to look at the effects of varying supersaturation and of inclusion of a simple inhibitor in the system. The behavior of the model is in accord with experiment. In general, increasing supersaturation causes earlier onset of crystallization. Crystallization in highly supersaturated systems involves liquid-liquid phase separation followed by nucleation in the solute phase. The nucleation event in such systems does not appear to be influenced by the solvent. Inclusion of inhibitors retards the onset. Additionally, extensive solute clustering is observed. The crystallization model and variations on it, as well as step by step extension to realistic systems, should enable further testing and development of theory of crystal nucleation and growth and provide insights of technological importance.