A Kinetic Study on the Isothermal Transition of Polymorphic Forms of Tolbutamide and Mefenamic Acid in the Solid State at High Temperatures

Abstract

The kinetics of the isothermal transition of tolbutamide polymorphic forms (form B at 65, 70, 75 and 80 °C), as well as mefenamic acid (form I at 142.5, 145, 147.5 and 150 °C) were investigated by means of differential scanning calorimetry. Kinetic analysis according to the method of Hancock and Sharp indicated that the transition of form B to form A of tolbutamide proceeds by the mechanism of three-dimensional diffusion (Jander equation). The activation energy for this transition calculated from the slope of the Arrhenius plots was 37.3 kcal/mol. On the other hand, the transition of form I to form II of mefenamic acid appeared to follow the zero-order mechanism (Polany-Winger equation). The activation energy for this transition was calculated to be 86.4 kcal/mol. © 1985, The Pharmaceutical Society of Japan. All rights reserved.