Engineers at the University of Leeds have now developed a way to avoid some of the problems caused by polymorphism. The simple technology can be used in existing chemical reactors to ensure “right first time” drug crystal formation. The team examined crystallisation of the COPT inhibitor, entacapone – which exhibits strong polymorphic behavior in aqueous/acetone solutions – with and without the presence of a self-assembled molecular layer of entacapone on a metal surface. The surfaces were found to act as nucleation catalysts, providing polymorph-specific templates: in the presence of self-assembled molecular layers, stable prismatic form A crystals were obtained from aqueous/acetone solutions compared to needle-shaped crystals of the metastable form D which would usually be obtained. If the procedure is as effective on an industrial scale, it could lead to consistent crystallisation of a desired polymorph (once identified!), through the selective choice of adsorbed species.
The study is published in a special edition of Crystal Growth & Design.