Template-induced nucleation of isonicotinamide polymorphs

By studying the potential of different heterogeneous templates to stimulate heterogeneous nucleation, this work aims to enhance the current knowledge of heterogeneous nucleation mechanisms and to obtain improved control of polymorphic selectivity in solution crystallization. The possibility of inducing nucleation of different isonicotinamide (INA) polymorphs by using heterogeneous templates, exhibiting porous and regular surfaces structures in the nanometer range, such as synthetic zeolite ZSM-5, mesoporous aluminosilicate MCM-41, and TiO₂ in both rutile and anatase phase, was investigated by monitoring in real-time the course of the crystallization process. Experiments demonstrated that all used templates were effective in reducing induction time, thus being successful in enhancing the nucleation rate of INA. Furthermore, the ability of the TiO₂ template in anatase form to induce the formation of a mixture of metastable forms I and III, thus diverting the expected course of polymorph crystallization due to INA self-association in ethanol, was demonstrated, providing an additional tool to achieve polymorphic selectivity in solution crystallization.