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Switching Polymorph Stabilities with Impurities: A Thermodynamic Route to Benzamide Form III
preprintsubmitted on 27.10.2020, 06:14 and posted on 28.10.2020, 11:47 by Weronika Kras, Andrea Carletta, Riccardo Montis, Rachel Sullivan, Aurora J. Cruz-Cabeza
We investigate the polymorphic behavior of benzamide, the first compound known to exhibit polymorphism, in the presence of small amounts of nicotinamide in the crystallization environment. A previous study by Emmerling et al.1 showed that the presence of nicotinamide promotes the transformation of the thermodynamic polymorph I of benzamide into its metastable polymorph III via mechanochemistry. We show that this transformation is the result of a thermodynamic switch between these two polymorphic forms driven by the formation of solid solutions with a small amount of nicotinamide. The presence of nicotinamide in the crystallization environment promotes the robust and exclusive crystallization of the elusive form III. These results represent a promising route to the synthesis and utilization of elusive polymorphs of pharmaceutical interest.