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

The crystal structure of the anhydrous phase of cimetidine hydrochloride was determined directly from powder X-ray diffraction data. The material was prepared bydehydration 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.

There are three dataset files.

The first, "Cimetidine HCl 13C NMR", consists of the raw and processed data for the 13C NMR spectrum of cimetidine HCl together with a text version of the processed spectrum.

The second, "Cimetidine HCl PXRD", consists of the raw and cpi versions of the two powder X-ray diffraction datasets acquired between 4° and 50° (Cimet HCl M) and between 6° and 70° (Cimet_long).

The third, "Cimetidine HCl magres", consists of the magres file generated by the program CASTEP when calculating NMR parameters from our crystal structure of cimetidine HCl.

Results derived from the data described here are published at http://dx.doi.org/10.1021/acs.cgd.6b00016