Some Physicochemical Properties of Glassy Indomethacin

Abstract

Glassy indomethacin was prepared, by cooling the melt, and the glassy state was confirmed by the jump of heat capacity and the anomalous endothermic peak (heat capacity maximum) in the differential scanning calorimetry (DSC) curve. The influences of the cooling rate of the melt and the heating rate of the glass formed on the glass transition temperature (Tg) were examined, and the apparent activation energy of glass transition was calculated to be 212.5kJ/mol. The relaxation process below Tg was traced in terms of the area under the anomalous endothermic peak of the DSC curve and the rate of relaxation during annealing was found to reach the maximum at about 303 K. The rate of dissolution of glassy indomethacin was far greater than that of crystalline indomethacin. Although indomethacin remained as a glass for 2 years at room temperature, pulverized glassy indomethacin was found to crystallize, and the rate of crystallization was determined by the X-ray diffraction method. The degree of crystallization was determined by Hermans’ method, and was found to reach a maximum of 60% after 2 months. The process of crystallization followed first-order kinetics. © 1986, The Pharmaceutical Society of Japan. All rights reserved.