Crystallization of Amorphous Nimesulide: The Relationship between Crystal Growth Kinetics and Liquid Dynamics.

Understanding crystallization and its correlations with liquid dynamics is relevant for developing robust amorphous pharmaceutical solids. Herein, nimesulide, a classical anti-inflammatory agent, was used as a model system for studying the correlations between crystallization kinetics and molecular dynamics. Kinetic parts of crystal growth () of nimesulide exhibited a power law dependence upon the liquid viscosity () as ~. Bulk molecular diffusivities () of nimesulide were predicted by a force-level statistical-mechanical model from the α-relaxation times, which revealed the relationship as ~. Bulk crystal growth kinetics of nimesulide in deeply supercooled liquid exhibited a fragility-dependent decoupling from . The correlations between growth kinetics and α-relaxation times predicted by the Adam-Gibbs-Vogel equation in a glassy state were also explored, for both the freshly made and fully equilibrated glass. These findings are relevant for the in-depth understanding and prediction of the physical stability of amorphous pharmaceutical solids.