Crystallisation of partially amorphous griseofulvin in water vapour: determination of kinetic parameters using isothermal heat conduction microcalorimetry

Griseofulvin was made partially amorphous by storing at its melting point and then rapidly cooling. The partially amorphous sample was seen to have a different differential scanning calorimetry profile to the starting crystalline material. The powder X-ray diffraction pattern of the starting and quenched materials were very similar, however, some evidence of an amorphous halo was seen for the quenched sample. Exposure to 65, 75 or 85% relative humidity (RI-I) in an isothermal microcalorimeter yielded an exotherm which was shown to be due to crystallisation of the amorphous content of the drug. The exotherm was modelled as a solid state reaction process to allow calculation of the rate constant, we believe this is the first time that such an experiment has been modelled to allow calculation of a rate constant. (C) 1998 Elsevier Science B.V. All rights reserved.