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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 τα and scaled as τα−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 τα, 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 us and surface relaxation times τsurface predicted by the random first-order transition theory. Here, the surface crystal growth rate us of GSF exhibited a power-law dependence upon the surface structural relaxation time: us ∝ τsurface−0.71, which was similar to that of the bulk growth rate and τα. These findings are important for understanding and predicting the crystallization of amorphous pharmaceutical solids both in the bulk and at the surface.

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Portable Document Format (PDF) file https://doi.org/10.1107/S1600576720014636/vb5002sup1.pdf
Dielectric loss spectra of griseofulvin and experiments for crystal growth in the bulk and at the free surface


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