Dissolution Phenomena of Organic Medicinals involving Simultaneous Phase Changes

Abstract

A model was proposed to analyze the dissolution phenomena involving simultaneous phase changes and its experimental demonstration was done with p-hydroxybenzoic acid and phenobarbital which change to the respective hydrates during dissolution. The mathematical expression for the dissolution according to this model was given by equation (3) or (4). Conbining the rotating disk method with the above equations, it was possible to determine the rate constant of crystallization process, kr, and the saturated concentration of anhydrate, C_SA, which are hardly obtainable by other usual methods. At the same time, the rate constant of transport process, kt, and the saturated concentration of hydrate, C_SH, were obtained. Analyzing the values of kt, kr, C_SA, and C_SH obtained at various temperatures, the activation energies of transport and crystallization process and the thermodynamic functions of the transition from anhydrate were determined, being reasonable compared with the past data reported on organic medicinals. The transition temperatures obtained from the intersections of the van't Hoff plots regarding anhydrate and hydrate were 84°for p-hydroxybenzoic acid and 37°for phenobarbital. In the case of p-hydroxybenzoic acid, (C_SA-C_SH) increased with temperature in the experimental temperature region.