A novel Raman spectroscopic approach to identify polymorphism in leflunomide: a combined experimental and theoretical study

Polymorphism is an important characteristic which affects the activity, solubility and other physical properties of a compound and can be induced by varying temperature, pressure and solvent. The presence and conversion of to polymorphic forms of an anti-rheumatic drug leflunomide have been studied by temperature-dependent and in situ Raman observations. Both and polymorphs were found to co-exist in the temperature interval 367-372K. The form alone exists below 367K and the form alone above 373K. The CO stretching band clearly demonstrates the conversion because of breaking of N-HO bond and formation of N-HN bond. On cooling the Raman spectra suggest the irreversibility of this conversion. Thermodynamic stability, crystal parameters and surface morphology of both forms in the leflunomide powder used for the present study have been verified by differential scanning calorimetry, X-ray powder diffraction and scanning electron microscopy. Copyright (c) 2015 John Wiley & Sons, Ltd.