A SPECTROSCOPIC INVESTIGATION OF LOSARTAN POLYMORPHS

Losartan, an antihypertensive agent in clinical development, was found to exist in two enantiotropic polymorphic forms, a low-temperature stable form (Form I) and a high-temperature stable form (Form II), the temperatures at which they are stable being related to the transition temperature. X-ray powder diffraction Patterns indicated differences in the crystal packing of the two forms. The vibrational data from infrared and Raman spectroscopy suggested a subtle change in molecular conformation and crystal packing in the two forms. Solid-state C-13 NMR data of the polymorphs concurred with the vibrational data and indicated that, while the observed line widths reflect no major changes in crystallinity, signal multiplicities and chemical shifts do reflect differences in molecular packing in the respective unit cells. Thus, in the absence of crystallographic data, useful structural information could be derived from spectroscopic results to identify each of the crystalline forms.