POLYMORPHISM OF DIFLUNISAL - ISOLATION AND SOLID-STATE CHARACTERISTICS OF A NEW CRYSTAL FORM

Three polymorphs (I, II, and III forms) and a new crystal form (form I V) of diflunisal were prepared and characterized by powder X-ray diffr actometry, differential scanning calorimetry (DSC), hot-stage microsco py, IR spectroscopy, and dissolution studies. According to the differe nt X-ray diffraction profiles, an identification system for the polymo rphs can be developed based on the different peak positions of the dif fraction patterns. The mutual transition behavior of the polymorphs wa s investigated and the melting points and melting enthalpies were dete rmined from DSC and thermomicroscopy data. All forms first recrystalli ze to the more stable form (form I) and then melt at 210 degrees C; on ly one weak transition peak was detected corresponding to transformati on of form III to form I. Differences observed in IR spectra indicate that intramolecular hydrogen bonding occurs between hydroxyl and carbo nyl groups and/or between fluorine atoms. The intrinsic dissolution ra tes were determined from compressed disks in an aqueous medium. Unexpe ctedly the dissolution rate of form IV was lower than that of the most stable modification form I.