Structure and Physicochemical Characterization of a Naproxen-Picolinamide Cocrystal

Kerr, H.E.; Softley, L.K.; Suresh, K.; Hodgkinson, P.; Evans, I.R.

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.

Citation

Kerr, H., Softley, L., Suresh, K., Hodgkinson, P., & Evans, I. (2017). Structure and Physicochemical Characterization of a Naproxen-Picolinamide Cocrystal. Acta Crystallographica Section C: Structural Chemistry, C73(3), https://doi.org/10.1107/s2053229616011980

• Journal Article Type: Article
• Acceptance Date: Jul 22, 2016
• Online Publication Date: Feb 6, 2017
• Publication Date: Mar 1, 2017
• Deposit Date: Jun 23, 2016
• Publicly Available Date: Feb 8, 2017
• Journal: Acta Crystallographica Section C: Structural Chemistry
• Electronic ISSN: 2053-2296
• Publisher: International Union of Crystallography
• Peer Reviewed: Peer Reviewed
• Volume: C73
• Issue: 3
• DOI: https://doi.org/10.1107/s2053229616011980
• Public URL: https://durham-repository.worktribe.com/output/1409162