Polymorphism of Diflunisal: Isolation and Solid-State Characteristics of a New Crystal Form

Abstract

Three polymorphs (I, II, and III forms) and a new crystal form (form IV) of diflunisal were prepared and characterized by powder X-ray diffractometry, differential scanning calorimetry (DSC), hot-stage microscopy, IR spectroscopy, and dissolution studies. According to the different X-ray diffraction profiles, an identification system for the polymorphs can be developed based on the different peak positions of the diffraction patterns. The mutual transition behavior of the polymorphs was investigated and the melting points and melting enthalpies were determined from DSC and thermomicroscopy data. All forms first recrystallize to the more stable form (form I) and then melt at 210 degrees C; only one weak transition peak was detected corresponding to transformation of form III to form I. Differences observed in IR spectra indicate that intramolecular hydrogen bonding occurs between hydroxyl and carbonyl groups and/or between fluorine atoms. The intrinsic dissolution rates were determined from compressed disks in an aqueous medium. Unexpectedly the dissolution rate of form IV was lower than that of the most stable modification form I.