Abstract
The dissolution behaviour of indomethacin (IMC) polymorphs, pure α and γ forms prepared by the method described in our previous paper, was investigated in detail. The solubility of α form was larger than that of γ form, and the heats of solution of α and γ forms obtained by the relationship between the solubility and temperature were 8.91 and 9.50 kcal/mol, respectively. The dissolution rate was measured by two methods, stationary disk and rotating disk methods. The heat of dissolution obtained by measurement of the initial dissolution rate at various temperatures was almost the same as that obtained by the two dissolution methods. The apparent dissolution rate constant, Kapp, the rate constants of interfacial chemical reaction and of transport process, Kr and Kt, and the diffusion coefficient, D were determined, and the activation energies of the interfacial chemical reaction and of the transport process were calculated by analyzing the values of Kr and Kt, respectively. The activation energies of the transport process of α and γ forms were the same value, 2.0 kcal/mol, and the activation energy of the interfacial chemical reaction of α form was larger than that of γ form. These results suggested that the dissolution of IMC proceeds with two processes of reaction and diffusion. Further, the laminar and turbulent flow were discussed in comparison with the two dissolution methods.
