Polymorphism on Leflunomide: Stability and Crystal Structures

Two polymorphs of Leflunomide were found and studied (form I and II). Both of them were characterized by X-ray powder diffraction and thermal analysis. Single crystals were obtained and both structures were solved. Forms I and II crystallize in the space group P21/c with two and one independent molecules per asymmetric unit, respectively. Thermodynamic stability of the two forms is assessed by differential scanning calorimetry. The cohesion in the crystal of form I (the more stable) is provided by both by H bonding as well as π … π interactions, while in form II it is given only by the former. The independent molecules in form I adopt different conformations thus allowing for a larger number of intermolecular interactions.