Structure determination of the theophylline-nicotinamide cocrystal: a combined powder XRD, 1D solid-state NMR, and theoretical calculation studyElectronic supplementary information (ESI) available: XRPD patterns, DSC curves, 15N CP/MAS NMR spectra of TP, NCT, and TP-NCT cocrystal and the TP-NCT structure after geometry optimization (in CIF format). See DOI: 10.1039/c4ce00012a

The crystal structure of a powder pharmaceutical cocrystal, theophylline-nicotinamide (1 : 1) crystal complex, is determined for the first time by using a combination of X-ray powder diffraction (XRPD), 1D solid state NMR, as well as density functional theory (DFT) calculations. With the aid of solid state NMR spectroscopy, a candidate structure can be determined from XRPD data by Rietveld refinement with acceptable residual variances. The structure was subjected to periodic geometry optimization, followed by NMR parameter calculations. The agreement between experimental and computed 13 C and 15 N NMR chemical shift values validates the refined structure as an accurate representation of the actual cocrystal structure. Intermolecular interactions existing in the cocrystal are further confirmed by the commonly used vibrational spectra. This study confirms that the straightforward synergistic approach offers a simple and credible way to solve the crystal structure of powder cocrystal samples. The crystal structure of the theophylline-nicotinamide cocrystal is determined for the first time by using a combined multi-technique approach.