Contact line crystallization to obtain metastable polymorphs

Crystallization of the metastable polymorph of paracetamol has been shown to occur around the edge of an evaporating aqueous solution. Conditions at the edge of a meniscus during evaporation led to an increase in solution concentration that allowed the nucleation of metastable crystals. This form was then unable to transform to the more stable polymorph via a solvent-mediated phase transformation because the crystals were removed from the solvent as the level of the solution dropped. These observations have been explained by analogies with previous reports of ring-shaped deposition, for example, salt crystallization and particle deposition from colloidal suspensions. This selective crystallization phenomenon is unlikely to be specific to paracetamol and may be applicable to the selective crystallization of metastable polymorphs of not only other pharmaceuticals but also other organic and inorganic materials. The conclusions drawn have particular relevance in the analysis of high-throughput crystallization experiments.