Thermodynamics, Molecular Mobility and Crystallization Kinetics of Amorphous Griseofulvin

Abstract

Griseofulvin is a small rigid molecule that shows relatively high molecular mobility and small configurational entropy in the amorphous phase and tends to readily crystallize from both rubbery and glassy states. This work examines the crystallization kinetics and mechanism of amorphous griseofulvin and the quantitative correlation between the rate of crystallization and molecular mobility above and below T_g. Amorphous griseofulvin was prepared by rapidly quenching the melt in liquid N₂. The thermodynamics and dynamics of amorphous phase were then characterized using a combination of thermal analysis techniques. After characterization of the amorphous phase, crystallization kinetics above T_g were monitored by isothermal differential scanning calorimetry (DSC). Transformation curves for crystallization fit a second-order John−Mehl−Avrami (JMA) model. Crystallization kinetics below T_g were monitored by powder X-ray diffraction and fit to the second-order JMA model. Activation energies for crystallization were markedly different above and below T_g suggesting a change in mechanism. In both cases molecular mobility appeared to be partially involved in the rate-limiting step for crystallization, but the extent of correlation between the rate of crystallization and molecular mobility was different above and below T_g. A lower extent of correlation below T_g was observed which does not appear to be explained by the molecular mobility alone and the diminishing activation energy for crystallization suggests a change in the mechanism of crystallization.