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Molecular packing in two polymorphs of sibenadet hydrochloride (AR-C68397AA, Viozan™) is investigated using a combined experimental 1H double-quantum (DQ) solid-state magic-angle spinning nuclear magnetic resonance and computational (gauge including projected augmented wave calculation of chemical shifts) approach. For Form I, NH–NH and NH–OH 1H DQ peaks are observed corresponding to nearest distances of 2.62 and 2.87 A, respectively, for the intermolecular hydrogen-bonding arrangement in the single-crystal X-ray diffraction structure. The same 1H DQ peaks at the same 1H chemical shifts are observed for Form II, for which there is no single-crystal diffraction structure, indicating the same intermolecular hydrogen-bonding arrangement of the benzothiazolone moieties as in Form I. 1H DQ build-up (as a function of the DQ recoupling time) curves are presented for the resolved NH–NH and NH–OH DQ peaks for the two polymorphs. For Form I, the ratio of the maximum intensity for the NH–OH and NH–NH DQ peaks is in excellent agreement with the ratio of the summed squares of the H–H dipolar couplings, as determined using H–H distances from the crystal structure up to 4 A. Small differences in the 1H DQ build-up behaviour for the two polymorphs are attributed to differences in the longer-range NH–OH distances associated with different inter-layer arrangements. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:1821–1830, 2012

With or without water? In under two hours, an NMR spectroscopy experiment can determine whether the anhydrous form of an active pharmaceutical ingredient is present in a tablet formulation. Such a high-resolution spectrum constitutes a new analytical tool that should be routinely adopted in the characterization of pharmaceuticals.