Dissolution and phase transition of pharmaceutical compounds

This paper presents a laboratory study of a solution-mediated phase transition of irbesartan form A into form B. The following stages are observed and studied: dissolution of form A until the apparent saturation is reached, form A dissolution which strictly compensates for the form B nucleation and growth, form A is completely dissolved and crystallization of form B is only observed until the concentration reaches the solubility of form B. In the first stages of the transformation, the dissolution of form A, we evidenced two distinct behaviors in function of undersaturation: (1) at higher undersaturation, dissolution is controlled by mass transfer and (2) at lower undersaturation, dissolution is controlled by surface process. The influence of the temperature is also shown. In the last part of this work we showed that from the knowledge of the crystal structure and experimental morphology additives can be selected. A surfactant, dodecyl amine chloride, has an accelerating effect on the dissolution of form A and hinder the growth of form B. Adipic acid slows down the dissolution rate of form A, but has no effect on the growth rate of form B. (C) 2002 Elsevier Science B.V. All rights reserved.