title: Structure and physicochemical characterization of a naproxen-picolinamide cocrystal.
abstract: Naproxen (NPX) is a nonsteroidal anti-inflammatory drug with pain- and fever-relieving properties, currently marketed in the sodium salt form to overcome solubility problems; however, alternative solutions for improving its solubility across all pH values are desirable. NPX is suitable for cocrystal formation, with hydrogen-bonding possibilities via the COOH group. The crystal structure is presented of a 1:1 cocrystal of NPX with picolinamide as a coformer [systematic name: (S)-2-(6-methoxynaphthalen-2-yl)propanoic acid-pyridine-2-carboxamide (1/1), C14H14O3·C6H6N2O]. The pharmaceutically relevant physical properties were investigated and the intrinsic dissolution rate was found to be essentially the same as that of commercial naproxen. An NMR crystallography approach was used to investigate the H-atom positions in the two crystallographically unique COOH-CONH hydrogen-bonded dimers.1H solid-state NMR distinguished the two carboxyl protons, despite the very similar crystallographic environments. The nature of the hydrogen bonding was confirmed by solid-state NMR and density functional theory calculations.
authors.affiliation: Department of Chemistry, Durham University, Lower Mountjoy, Stockton Road, Durham DH1 3LE, UK.
authors.forename: Hannah E
authors.initials: HE
authors.lastname: Kerr
authors.affiliation: Department of Chemistry, Durham University, Lower Mountjoy, Stockton Road, Durham DH1 3LE, UK.
authors.forename: Lorna K
authors.initials: LK
authors.lastname: Softley
authors.affiliation: School of Chemistry, University of Hyderabad, Hyderabad 500 046, India.
authors.forename: Kuthuru
authors.initials: K
authors.lastname: Suresh
authors.affiliation: Department of Chemistry, Durham University, Lower Mountjoy, Stockton Road, Durham DH1 3LE, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Hodgkinson
authors.affiliation: Department of Chemistry, Durham University, Lower Mountjoy, Stockton Road, Durham DH1 3LE, UK.
authors.forename: Ivana Radosavljevic
authors.initials: IR
authors.lastname: Evans
keywords: DFT analysis; NMR crystallography; cocrystal; computational chemistry; crystal structure; dimers; hydrogen bonding; naproxen; pharmaceuticals; picolinamide