Novel anhydrous solid-state form of Azathioprine: The assessing of crystal structure by powder X-Ray diffraction, Infrared Absorption Spectroscopy and Raman scattering

Abstract Azathioprine (Imuran), one of the oldest immunosuppressants, having been used in transplantation since the early 1960`s, is known to have only two crystal forms: an anhydrous form and a dihydrate phase. We report the crystal structure of a new anhydrous solid-state form of Azathioprine, determined directly form powder X-Ray diffraction data, employing the direct-space genetic algorithm technique for structure solution, followed by Rietveld refinement. The new anhydrous polymorph is accessible only by a solid-state dehydration process of the readily obtained monohydrate form of Azathioprine, the form for which a crystal structure has not previously been reported. The IR and Raman spectra confirmed the results obtained from X-Ray diffraction indicating the presence of all functional groups involved in intermolecular hydrogen bonding which dictates different arrangement of molecules in the structural packing.