Geometric Design of Heterogeneous Nucleation Sites on Biocompatible Surfaces

Biocompatible polymer surfaces imprinted with nanopores of various geometries were utilized as heteronucleants during crystallizations of mefenamic acid (MA). MA, a nonsteroidal anti-inflammatory drug (NSAID) that possesses two structurally characterized polymorphs, is utilized as a model compound. By combining geometric nanoconfinement and favorable surface–solute interactions, it was possible to influence the nucleation kinetics of this system and harvest the metastable form of MA, MA form II, on the square nanopores. An exploration of the relationship between the preferred orientation found by powder X-ray diffraction (PXRD) and the angular matching based on the intrinsic angles, determined by the predicted morphology, was used to provide insights into the mechanism for the observed nucleation enhancement and polymorph selection. The results presented here might lead to a rational design strategy of surfaces to control nucleation and, therefore, polymorphism.