The effect of pulverization on the
dehydration behavior of 2-[(2-methylimidazol-1-yl)methyl]benzo[i]thiochromen-1-one monohydrochloride hemihydrate (GK-128), a newly developed serotonin3 receptor antagonist, was studied using
powder X-ray diffraction analysis, thermogravimetry (TG), and differential scanning calorimetry (DSC). The crystalline forms of
GK-128 obtained by pulverizing with a jet mill and an agale mortar were each confirmed to be the same as that of intact
GK-128, since the
powder X-ray diffraction patterns of the two prepared samples were identical with that of intact
GK-128. However, after pulverization by jet mill, the
dehydration temperature of
GK-128 was markedly lowered and the DSC endothermic peak due to
dehydration disappeared. The activation energy for
dehydration, calculated by the Ozawa method using TG data, decreased with decreasing particle size and/or crystallinity of
GK-128 crystals, e.g., the activation energies for
dehydration of intact and jet-milled
GK-128 were 128.1 and 75.9 kj/mol, respectively. The results of comparison of
powder X-ray diffraction patterns of pulverized
GK-128 and intact
GK-128 and of determination of the crystal structure of
GK-128 suggested that water molecules could be removed easily along the c-axis of
GK-128 crystals.