Acceleration of Crystal Growth of Amorphous Griseofulvin by Low-Concentration Poly(ethylene oxide): Aspects of Crystallization Kinetics and Molecular Mobility.

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 Tg. The overlapping of α-relaxation times of GSF in presence and absence of PEO as a function of Tg/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 Tg/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.