AN INVESTIGATION OF FLURBIPROFEN POLYMORPHISM BY THERMOANALYTICAL ANDSPECTROSCOPIC METHODS AND A STUDY OF ITS INTERACTIONS WITH POLY-(ETHYLENE GLYCOL)-6000 BY DIFFERENTIAL SCANNING CALORIMETRY AND MODELING

The polymorphism of flurbiprofen was investigated. The flurbiprofen-PE G 6000 phase diagram was constructed and compared with the modelling d iagram in order to examine interactions between the two compounds. The rmoanalytical (differential scanning calorimetry, transparency measure , thermomicroscopy) and spectral methods (infrared spectroscopy and X- ray diffraction) were used to identify the polymorphic forms and to co nstruct the phase diagram. Thermodynamic data were used to model the f lurbiprofen-PEG 6000 system. Two polymorphic forms were identified (T- fI = 112.8 +/- 0.2 degrees C, Delta H-I = 108.1 +/- 3.2 J/g and T-fII = 97.0 +/- 0.2 degrees C) along with a probable enantiotropic transiti on of form II into form I at 60 degrees C. The construction of the flu rbiprofen-PEG 6000 phase diagram showed the existence of a stable inva riant characterized by (X-E)exp = 67% of PEG 6000 (w/w) and (T-fE)exp = 48.0 +/- 0.2 degrees C. Modelling confirmed these results with (X-E) exp = 67% of PEG 6000 (w/w) and (T-fE)th = 53.3 +/- 0.2 degrees C and was used to evaluate chi = -2.67. The Flory-Huggins parameter 'chi' wa s evaluated from the model. Its value confirms the existence of intera ctions due to hydrogen bonds. (C) 1997 Elsevier Science B.V.