Demonstration of the Terms Enantiotropy and Monotropy in Polymorphism Research Exemplified by Flurbiprofen

The thermodynamic terms enantiotropy and monotropy are demonstrated by means of solid‐state analytical results of polymorphous flurbiprofen (FBP). Vibrational spectra, differential scanning calorimetry (DSC), and thermomicroscopy investigations as well as X‐ray powder patterns for three modifications of FBP are described. The melting points are mod. I 113–114 °C (enthalpy of fusion 27.9 ± 0.2 kJ mol−1) for modification I (mod. I), 92 °C for mod. II, and 87 °C for mod. III. The true densities of mod. I (1.279 ± 0.001 g cm−3) and mod. II (1.231 ± 0.002 g cm−3) were measured at 25 °C. Modification I (commercial product) is the thermodynamically stable crystal form from absolute zero to its melting point. Modification II was crystallized on a gram scale from a warm saturated solution of FBP in n‐heptane and rapid cooling of the solution to −18 °C. Modification I is monotropically related to mod. II and mod. III, due to application of the density rule and the entropy‐of‐fusion rule. The thermodynamic relationships between the three modifications are demonstrated by a semischematic energy/temperature diagram. Theoretical vapor pressure/temperature diagrams and energy/temperature diagrams are compared and briefly discussed.