title: The challenging case of the theophylline-benzamide cocrystal.
abstract: Theophylline has been used as an active pharmaceutical ingredient (API) in the treatment of pulmonary diseases, but due to its low water solubility reveals very poor bioavailability. Based on its different hydrogen-bond donor and acceptor groups, theophylline is an ideal candidate for the formation of cocrystals. The crystal structure of the 1:1 benzamide cocrystal of theophylline, C7H8N4O2·C7H7NO, was determined from synchrotron X-ray powder diffraction data. The compound crystallizes in the tetragonal space group P41 with four independent molecules in the asymmetric unit. The molecules form a hunter's fence packing. The crystal structure was confirmed by dispersion-corrected DFT calculations. The possibility of salt formation was excluded by the results of Raman and (1)H solid-state NMR spectroscopic analyses.
authors.affiliation: BAM Federal Institute for Materials Research and Testing, R.-Willstätter-Strasse 11, Berlin 12489, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Fischer
authors.affiliation: Goethe-Universität, Institut für Anorganische und Analytische Chemie, Max-von-Laue-Strasse 7, Frankfurt am Main 60438, Germany.
authors.forename: Martin U
authors.initials: MU
authors.lastname: Schmidt
authors.affiliation: BAM Federal Institute for Materials Research and Testing, R.-Willstätter-Strasse 11, Berlin 12489, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Greiser
authors.affiliation: BAM Federal Institute for Materials Research and Testing, R.-Willstätter-Strasse 11, Berlin 12489, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Emmerling
mesh_terms: D001549:Benzamides / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D011789:Quantum Theory; D013059:Spectrum Analysis, Raman; D013806:Theophylline / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D001549:Benzamides; D013806:Theophylline
keywords: active pharmaceutical ingredient; benzamide; cocrystal; crystal structure; dispersion-corrected density-functional theory; powder diffraction; theophylline