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 degreesC (enthalpy of fusion 27.9 +/- 0.2 kJ mol-1) for modification I (mod. I), 92 degreesC for mod. II, and 87 degreesC 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 degreesC. 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 degreesC. 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.
Henck
J O
JO
Institut für Pharmakognosie der Universität Innsbruck, Josef-Moeller-Haus, Innrain 52, A-6020 Innsbruck, Austria. Jan-Olav.Henck@uibk.ac.at
Kuhnert-Brandstätter
M
M
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D018360:Crystallography, X-Ray; D003720:Densitometry; D019277:Entropy; D005480:Flurbiprofen / Q000737:chemistry*; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D013816:Thermodynamics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012997:Solvents; D005480:Flurbiprofen