Thermo-Structural Characterization of Phase Transitions in Amorphous Griseofulvin: From Sub-Tg Relaxation and Crystal Growth to High-Temperature Decomposition

Abstract

The processes of structural relaxation, crystal growth, and thermal decomposition were studied for amorphous griseofulvin (GSF) by means of thermo-analytical, microscopic, spectroscopic, and diffraction techniques. The activation energy of similar to 395 kJ center dot mol(-1) can be attributed to the structural relaxation motions described in terms of the Tool-Narayanaswamy-Moynihan model. Whereas the bulk amorphous GSF is very stable, the presence of mechanical defects and micro-cracks results in partial crystallization initiated by the transition from the glassy to the under-cooled liquid state (at similar to 80 degrees C). A key aspect of this crystal growth mode is the presence of a sufficiently nucleated vicinity of the disrupted amorphous phase; the crystal growth itself is a rate-determining step. The main macroscopic (calorimetrically observed) crystallization process occurs in amorphous GSF at 115-135 degrees C. In both cases, the common polymorph I is dominantly formed. Whereas the macroscopic crystallization of coarse GSF powder exhibits similar activation energy (similar to 235 kJ center dot mol(-1)) as that of microscopically observed growth in bulk material, the activation energy of the fine GSF powder macroscopic crystallization gradually changes (as temperature and/or heating rate increase) from the activation energy of microscopic surface growth (similar to 105 kJ center dot mol(-1)) to that observed for the growth in bulk GSF. The macroscopic crystal growth kinetics can be accurately described in terms of the complex mechanism, utilizing two independent autocatalytic Sestak-Berggren processes. Thermal decomposition of GSF proceeds identically in N-2 and in air atmospheres with the activation energy of similar to 105 kJ center dot mol(-1). The coincidence of the GSF melting temperature and the onset of decomposition (both at 200 degrees C) indicates that evaporation may initiate or compete with the decomposition process.