Fast Crystal Growth of Amorphous Griseofulvin: Relations between Bulk and Surface Growth Modes

Abstract

Griseofulvin (GSF), a poorly water-soluble antifungal drug, is a model system for studying the physical stability of amorphous pharmaceuticals. In this study, we examined the crystallization kinetics of GSF in the bulk and at the surface as a function of temperature. A sudden 10-fold rise of bulk crystal growth rate was observed near Tg, a phenomenon similar to that observed in other molecular glasses and termed glass-to-crystal (GC) growth. Also analogous to other molecular glasses, GSF grows crystals much faster at the free surface than in the bulk. What distinguishes GSF from other systems is that surface crystallization can occur well above Tg (up to Tg + 62 °C). Another peculiar feature of GSF is that during bulk crystal growth at 130–150 °C, some crystals protruded well ahead of the normal growth front at the same growth rate as surface crystals. We suspect this protruding crystal growth is a surface-facilitated process through the formation of voids and free surfaces during bulk crystal growth. These new findings are important for understanding the mechanisms and connections for the bulk and surface crystallization in amorphous pharmaceutical solids.