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 st able form (Form I) and a high-temperature stable form (Form II), the t emperatures at which they are stable being related to the transition t emperature. X-ray powder diffraction Patterns indicated differences in the crystal packing of the two forms. The vibrational data from infra red and Raman spectroscopy suggested a subtle change in molecular conf ormation and crystal packing in the two forms. Solid-state C-13 NMR da ta of the polymorphs concurred with the vibrational data and indicated that, while the observed line widths reflect no major changes in crys tallinity, signal multiplicities and chemical shifts do reflect differ ences 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 crystall ine forms.