Crystallization of polymorphs: the effect of solvent

Abstract

The effect of solvent in crystallization of polymorphs has been studied using the drug sulphathiazole as a model compound. The solubilities of the four polymorphic forms of sulphathiazole were determined as a function of temperature in various solvents. Within the temperature ranges studied, the rank order of solubility of the polymorphs was the same in all solvent systems. On the basis of this knowledge of the temperature dependence of the solubilities, recrystallization experiments, in which the supersaturation was systematically varied, were carried out in an endeavour to isolate each of the polymorphic forms from each solvent system. These recrystallization experiments reveal that not all of the know polymorphic forms can be crystallized from any given solvent by varying the supersaturation. Indeed some solvents selectively favour the crystallization of a particular form of forms. The authors conclude that thermodynamic effects are not responsible for the selective behaviour of a solvent. A kinetic mechanism is proposed. It is considered that the solvent acts by selective adsorption to certain faces of some of the polymorphs, and thereby either inhibits their nucleation or retards their growth to the advantage of others.