Inclusion of the Stable Form of a Polymorph within Crystals of Its Metastable Form

Abstract

We have used a variety of microscopy and spectroscopy techniques to study the crystal interior of l-glutamic acid (l-Glu) during a solvent-mediated polymorphic transformation process. Remarkably, we have found the encapsulation of the stable form of l-Glu within the metastable form. In particular, we have verified the encapsulation using the novel approach of focused ion beam microscopy, which although extensively used in the semiconductor industry, has not previously been used in the study of polymorphism. It has long been predicted that during cooling crystallization, nucleation of more than one polymorph can occur at any one time, if the solution is supersaturated with respect to more than one form. This work presents experimental evidence to support this hypothesis. On the basis of these results, we propose a new mechanism for polymorphic transformation, with implications for the crystal growth of every compound that exhibits polymorphism.