A kinetic study of the crystallization process of noncrystalline indomethacin under isothermal conditions1)

Abstract

The crystallization process of noncrystalline indomethacin (IMC) obtained by the grinding and by the fusion method was analyzed by a kinetic method. The noncrystalline samples of IMC were the a form ground for 10 h at 4°C (GNCα), the γ form ground for 10h at 4°C (GNCγ) and the fused solid (NC). Ten kinetic models were employed, and crystallinity was determined by X-ray diffractometry. Data obtained were used to determine the thermodynamic parameters and crystallization mechanism. Under isothermal conditions GNCa crystallized in both the α and γ forms simultaneously. The GNCγ and NC crystallized in the γ form, and the results of the Hancock-Sharp method suggested that both crystallizations occurred by a two-dimensional phase boundary reaction: the activation energies (E) were estimated to be 24.1 and 27.2 kcal/mol. The crystallization rate of GNCγ was about 60 times faster than that of NC, and therefore NC was a very stable noncrystalline solid. These results suggest that there are several kinds of noncrystalline solids. © 1988, The Pharmaceutical Society of Japan. All rights reserved.