Crystallisation of Polymorphs:  Thermodynamic Insight into the Role of Solvent

Dependent on the conditions, crystallisation of polymorphs from solvent may be under kinetic or thermodynamic control. In the latter case the nature of the solvent will be immaterial in respect of the polymorph produced. The conditions under which each of these factors may apply are analysed in detail. The transition point between two dimorphs may not present a sharp divide in which crystallisation above and below the transition temperature produces the high melting and the low melting polymorph, respectively. It is shown that even in those cases where the choice of solvent appears to be critical this may be a secondary effect related to the concentration attainable in that solvent at a certain temperature rather than a specific effect dependent on solvent−solute interaction. A corollary to these considerations is the necessity to determine solubility curves and metastable zone widths in order to be able to control polymorph crystallisation.