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 (u(kin)) of nimesulide exhibited a power law dependence upon the liquid viscosity (η) as u(kin)~η(−0.61). Bulk molecular diffusivities (D(Bulk)) of nimesulide were predicted by a force-level statistical–mechanical model from the α-relaxation times, which revealed the relationship as u(kin)~D(bulk)(0.65). Bulk crystal growth kinetics of nimesulide in deeply supercooled liquid exhibited a fragility-dependent decoupling from τ(α). 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.