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 ~395 kJ·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 ~80 °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 °C. In both cases, the common polymorph I is dominantly formed. Whereas the macroscopic crystallization of coarse GSF powder exhibits similar activation energy (~235 kJ·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 (~105 kJ·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 Šesták-Berggren processes. Thermal decomposition of GSF proceeds identically in N2 and in air atmospheres with the activation energy of ~105 kJ·mol-1. The coincidence of the GSF melting temperature and the onset of decomposition (both at 200 °C) indicates that evaporation may initiate or compete with the decomposition process.

• Keywords
• DSC, amorphous griseofulvin, crystal growth, particle size, structural relaxation,
• Publication type
• Journal Article MeSH

The influence of partial crystallinity on the structural relaxation behavior of low-molecular organic glasses is, contrary to, e.g., polymeric materials, a largely unexplored territory. In the present study, differential scanning calorimetry was used to prepare a series of amorphous indomethacin powders crystallized to various extents. The preparations stemmed from the two distinct particle size fractions: 50-125 µm and 300-500 µm. The structural relaxation data from the cyclic calorimetric measurements were described in terms of the phenomenological Tool-Narayanaswamy-Moynihan model. For the 300-500 µm powder, the crystalline phase forming dominantly on the surface led to a monotonous decrease in the glass transition by ~6 °C in the 0-70% crystallinity range. The activation energy of the relaxation motions and the degree of heterogeneity within the relaxing matrix were not influenced by the increasing crystallinity, while the interconnectivity slightly increased. This behavior was attributed to the release of the quenched-in stresses and to the consequent slight increase in the structural interconnectivity. For the 50-125 µm powder, distinctly different relaxation dynamics were observed. This leads to a conclusion that the crystalline phase grows throughout the bulk glassy matrix along the internal micro-cracks. At higher crystallinity, a sharp increase in Tg, an increase in interconnectivity, and an increase in the variability of structural units engaged in the relaxation motions were observed.

• Keywords
• TNM model, crystallinity, indomethacin, structural relaxation,
• MeSH
• Calorimetry, Differential Scanning MeSH
• Indomethacin * chemistry   MeSH
• Crystallization MeSH
• Powders MeSH
• Temperature MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Indomethacin * MeSH
• Powders MeSH