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 T g, 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 T g (up to T g + 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.

In recent years, the coamorphous drug delivery system has been established as a promising formulation approach for delivering poorly water-soluble drugs. The coamorphous solid is a single-phase system containing an active pharmaceutical ingredient (API) and other low molecular weight molecules that might be pharmacologically relevant APIs or excipients. These formulations exhibit considerable advantages over neat crystalline or amorphous material, including improved physical stability, dissolution profiles, and potentially enhanced therapeutic efficacy. This review provides a comprehensive overview of coamorphous drug delivery systems from the perspectives of preparation, physicochemical characteristics, physical stability, in vitro and in vivo performance. Furthermore, the challenges and strategies in developing robust coamorphous drug products of high quality and performance are briefly discussed.

This study aims to investigate the crystallization behavior and molecular dynamics of amorphous griseofulvin (GSF) in the presence of low-concentration poly(ethylene oxide) (PEO). We observe that the addition of 3% w/w PEO remarkably increases the crystal growth rate of GSF by two orders of magnitude in both the supercooled liquid and glassy states. The liquid dynamics of amorphous GSF in the presence and absence of PEO are characterized by dielectric spectroscopy. With an increase of the PEO content, the α-relaxation times of the systems decrease, indicating the increase of global molecular mobility. The couplings between molecular mobility and crystallization kinetics of GSF systems show strong time-dependences below T. The overlapping of α-relaxation times of GSF in presence and absence of PEO as a function of T/T suggest the "plasticization" effect of PEO additives. However, the crystallization kinetics of amorphous GSF containing low-concentration PEO do not overlap with those of pure GSF on a T/T scale. The remarkable accelerating effect of crystal growth of amorphous GSF by low-concentration PEO can be partially attributed to the increase of global mobility. The high segmental mobility of PEO is expected to strongly affect the crystal growth rates of GSF. These findings are relevant for understanding and predicting the physical stability of amorphous pharmaceutical solid dispersions.

Griseofulvin (GSF) is a classic antifungal drug that has been in clinical use for over 50 years, but its polymorphism was recognized only recently via melt crystallization. Here we report the structure of a single crystal of GSF form II which was unusually harvested from the supercooled melt. GSF form II exhibits an anomalously large thermal expansion coefficient.

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