Combining the Advantages of Powder X-ray Diffraction and NMR Crystallography in Structure Determination of the Pharmaceutical Material Cimetidine Hydrochloride

We report the crystal structure of the anhydrous phase of cimetidine hydrochloride, determined directly from powder X-ray diffraction data. The material was prepared by dehydration of the readily obtained monohydrate form of cimetidine hydrochloride, the only form for which a crystal structure has previously been reported. As such, solid-state dehydration processes typically yield the product phase as a microcrystalline powder, and structure determination was carried out directly from powder X-ray diffraction data, using the direct-space genetic algorithm technique for structure solution followed by Rietveld refinement. The structure determined from powder X-ray diffraction was further validated by calculating solid-state ¹³C NMR data for the crystal structure (using first-principles periodic DFT techniques within the GIPAW approach) and assessing the quality of agreement with the corresponding experimental solid-state ¹³C CPMAS NMR data. This strategy provides a robust vindication of the correctness of the crystal structure by assessing the quality of agreement of the structure both with experimental powder X-ray diffraction data and with experimental solid-state ¹³C NMR data.