PHYSICOCHEMICAL CHARACTERIZATION OF FUROSEMIDE MODIFICATIONS

The polymorphism of furosemide has been extensively investigated and characterized using X-ray powder diffractometry, differential scanning calorimetry, infrared and Fourier transform infrared spectroscopy, elemental analysis, hot-stage microscopy and scanning electron microscopy. Comparative analysis of the results reported by Doherty and York (1988) with the present data was performed to a high degree of precision in order to determine the points of agreement and difference between the two studies. The aforementioned authors investigated only two polymorphs (one stable and one metastable form), contrasting with our findings of five new types of modification (two polymorphs, two solvates and one amorphous form) in addition to the crystal forms. Among the seven modifications, enantiotropism was observed between two stable forms (low- and high-temperature-stable forms). On heating, the two metastable forms underwent transformation directly to the high-temperature-stable form whereas the situation in the case of the solvates involved progression via the intermediate stage of the low-temperature-stable form. The thermodynamic stability of these four polymorphs is discussed in relation to the activation energy and heat of transformation. A distinctly different degree of physicochemical photostability (coloration) was evident among the modifications; although the stable form did not show significant coloration even when irradiated with intense light, the other crystal forms were very susceptible to coloration. One of the metastable forms (form (III)) far surpassed any of the other crystal forms in dissolution properties. © 1990.