Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Physico-chemical Properties and Isothermal Transition of Acetazolamide Polymorphs
TSUNEO UMEDANORIAKI OHNISHITERUYOSHI YOKOYAMATSUTOMU KURODAYOSHIAKI KITAKOJI KURODAETSUKO TATSUMIYOSHIHISA MATSUDA
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Keywords: kinetic analysis
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1985 Volume 33 Issue 8 Pages 3422-3428

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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.
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© The Pharmaceutical Society of Japan
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