1985 Volume 33 Issue 8 Pages 3447-3455
Methods for the preparation of polymorphs of indomethacin (IMC) were studied in order to obtain the pure polymorphs. The physicochemical properties of IMC polymorphs were measured by using X-ray diffraction analysis. infrared (IR) spectroscopy, differential thermal analysis (DTA) and differential scanning calorimetry (DSC), and two polymorphs (α and γ forms) and one benzene solvate (β form) were identified. The pure α form was obtained when distilled water at room temperature was poured into IMC ethanol solution at about 80°C, and the precipitated crystals were filtered off and dried. The pure β and γ forms were obtained by recrystallization from benzene and ethyl ether, respectively, at room temperature. The melting points of the α and γ forms were 148 and 154°C, respectively, and their heats of fusion were 7.49±0.27 and 8.64±0.13kcal/mol, respectively, as determined by DSC. A mixture of α and γ forms was obtained by the method previously reported for α form preparation ("recrystallization method"), since the pure α form was transformed to the γ form in ethanol at room temperature. The transformation of α form to γ form in ethanol was analyzed by the kinetic method using 9 kinds of kinetic models. It was concluded that the transformation followed kinetics corresponding to two-dimensional growth of nuclei (Avrami equation), and the activation energy was calculated to be 14.2 kcal/mol from the Arrhenius plot. The solubilities of the α and γ forms in distilled water were 0.87 and 0.69mg/100ml, respectively.