A solid-form landscape of the drug substance iproniazid (IPN) was investigated to elucidate its polymorphic phase behavior and relative stability. A multi-technique approach, employing thermal analysis, sublimation, solubility, and solution calorimetry, provided a thorough characterization of IPN polymorphs. Form I was confirmed as the most thermodynamically stable polymorph of the drug under ambient conditions. Lattice energy calculations corroborated the experimental findings, showing that form I has the lowest energy. The study demonstrated that the selective formation of metastable forms II and III can be kinetically controlled by specific processing parameters, including the duration of mechanical grinding, the composition of the dissolution medium in freeze-drying experiments, and temperature. These findings provide a complete thermodynamic and kinetic framework for controlling the solid-state form of IPN, which is crucial for its pharmaceutical development.
