Diffusion-controlled and `diffusionless' crystal growth: relation between liquid dynamics and growth kinetics of griseofulvin

Understanding how liquid dynamics govern crystallization is critical for maintaining the physical stability of amorphous pharmaceutical formulations. In the present study, griseofulvin (GSF), a classic antifungal drug, was used as the model system to investigate the correlations between crystal growth kinetics and liquid dynamics. The temperature dependence of the kinetic part of the bulk crystal growth in a supercooled liquid of GSF was weaker than that of the structural relaxation time τ_α and scaled as τ_α^−0.69. In the glassy state, GSF exhibited the glass-to-crystal (GC) growth behavior, whose growth rate was too fast to be under the control of the α-relaxation process. Moreover, from the perspective of τ_α, the GC growth of GSF also satisfied the general condition for GC growth to exist: D/u < 7 pm, where D is the diffusion coefficient and u the speed of crystal growth. Also compared were the fast surface crystal growth rates u_s and surface relaxation times τ_surface predicted by the random first-order transition theory. Here, the surface crystal growth rate u_s of GSF exhibited a power-law dependence upon the surface structural relaxation time: u_s ∝ τ_surface^−0.71, which was similar to that of the bulk growth rate and τ_α. These findings are important for understanding and predicting the crystallization of amorphous pharmaceutical solids both in the bulk and at the surface.