Switching Nitrofurantoin Polymorphic Outcome in Solvent-Mediated Phase Transformation and Crystallization Using Solvent and Additives

We demonstrate that several additives and solvents allow switching the polymorphic outcome of solvent-mediated phase transformation experiments and crystallization of the antibacterial drug nitrofurantoin. Polymorph β is obtained from most of the solvents, whereas the selection of alcohols as solvents or the use of crystallization additives provides the formation of polymorph α. We also demonstrate that this can be linked to reversed apparent relative solubility of nitrofurantoin polymorphs in these solvents or in the presence of the respective additives. We propose that this could be caused by different surface–additive and surface–solvent interactions formed by each of the nitrofurantoin polymorphs, which would change the relative surface energy of polymorphs.