CRYSTALLIZATION OF PARTIALLY AMORPHOUS GRISEOFULVIN IN WATER-VAPOR - DETERMINATION OF KINETIC-PARAMETERS USING ISOTHERMAL HEAT-CONDUCTION MICROCALORIMETRY

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