Dissolution Phenomenon of the Piretanide Amorphous Form Involving Phase Change.

Abstract

The dissolution phenomenon of piretanide amorphous form and form C was investigated in various pH buffers at 37°C and at pH 5 at various temperatures by a dispersed-amount method. Their initial dissolution rates were investigated at pH 5 at various temperatures (30-45°C) by a stationary-disk method. The solubility of the amorphous form and form C was temperature dependent at pH 5 and pH dependent at 37°C. The amorphous form was more soluble than form C under acidic conditions. However, it was as soluble as form C in JP XII second fluid (pH 6.8). The amorphous form showed characteristic convex dissolution curves with maximal concentration at 30 and 35°C, whereas the amorphous form at 40 and 45°C and the form C at 30-45°C showed only normal dissolution curves.The initial dissolution process of form C obtained by the stationary-disk method followed the Noyes-Whitney-Nernst equation, but that of the amorphous form did not. The initial dissolution process of the amorphous form was analyzed by a dissolution kinetics equation involving phase transformation from the amorphous form to form C. The maximal concentration, the dissolution rate constant, and the rate constant of the phase transition process were estimated. The thermodynamic parameters for the dissolution process of the amorphous form and form C were obtained from van't Hoff and Arrhenius plots, respectively. The results of the intrinsic solubility and dissolution parameters of the two forms suggested that the difference in the dissolution rates between them affects the bioavailability of piretanide preparations.