Abstract
Acetazolamide has two polymorphic forms (forms A and B), which were characterized by X-ray powder diffractometry, infrared spectrophotometry, differential scanning calorimetry and thermogravimetry. The solubility and dissolution rate of form B were about 1.1 times higher than those of form A. The transition temperature obtained by solubility measurement was 78°C, and the heats of transition (ΔHtrans) calculated by solubility measurement and by differential scanning calorimetry were 2.6 and 1.7 kJ·mol-1, respectively. The free energy change (ΔG25c) between the two polymorphic forms was calculated to be 357 J·mol-1. In addition, the kinetics of isothermal transition of form A to form B at high temperature was investigated by means of differential scanning calorimetry ; this transition appeared to follow the mechanism of random nucleation with first-order kinetics. The activation energy for this transition was calculated to be 246 kJ·mol-1 from the Arrhenius plots.