ISOLATION AND SOLID-STATE CHARACTERISTICS OF A NEW CRYSTAL FORM OF INDOMETHACIN

A new polymorphic crystal form of indomethacin was precipitated from an aqueous solution of indomethacin and beta-cyclodextrin by titration with a 0.5 N HCl aqueous solution. Three polymorphs (alpha, beta, and gamma-forms) and a new crystal form were differentiated with thermal analysis, infrared spectroscopy, powder X-ray diffractometry, thin-layer chromatography, elemental analysis, and Fourier transform infrared (FTIR) spectroscopy with a newly developed FTIR microscope equipped with a thermal analyzer. The new crystal polymorph of indomethacin exhibited endo- and exothermic peaks near 102.8 and 104.1-degrees-C, respectively, because of phase transitions without weight loss, followed by two additional endothermic peaks at 151 and 158.9-degrees-C, because of fusion. The differential scanning calorimetry-FTIR system can be used to examine the correlation between structural change of C = O stretching bands of this new polymorph and its thermal response. The new crystal form contained some gamma-form crystals, determined with an FTIR microscope equipped with a mapping option. Solid-state carbon-13 nuclear magnetic resonance spectra of the polymorphs of indomethacin were also examined.