Jump to main content
Jump to site search

Issue 35, 2015
Previous Article Next Article

A furosemide–isonicotinamide cocrystal: an investigation of properties and extensive structural disorder

Author affiliations

Abstract

Furosemide is a loop diuretic drug marketed in solid form which suffers from low solubility and low permeability. The pharmaceutically relevant properties of a recently described furosemide–isonicotinamide 2 : 1 cocrystal (2FS–INA) were investigated and compared with those of other known furosemide cocrystals. The intrinsic dissolution rate of 2FS–INA was found to be very similar to that of commercial FS, while its equilibrium solubility was 5.6 times higher than that of pure FS. The extensive structural disorder in 2FS–INA observed by diffraction methods was also investigated by variable-temperature solid-state NMR in conjunction with first principles calculations. 15N NMR confirmed the absence of proton disorder in the short OH⋯N hydrogen bond. The disordered sulphonamide group was found to be dynamic by variable temperature 2H experiments, involving fast exchange of the sulphonamide NH2 protons combined with a rotation of the whole sulphonamide group about the C–S bond. The disorder of the furan rings of both the unique furosemide molecules was also found to be dynamic by 13C experiments, with approximately the same activation barrier for both rings.

Graphical abstract: A furosemide–isonicotinamide cocrystal: an investigation of properties and extensive structural disorder

  • This article is part of the themed collection: HOT articles
Back to tab navigation

Supplementary files

Publication details

The article was received on 18 Jun 2015, accepted on 29 Jul 2015 and first published on 30 Jul 2015


Article type: Paper
DOI: 10.1039/C5CE01183C
Author version
available:
Download author version (PDF)
CrystEngComm, 2015,17, 6707-6715
  • Open access: Creative Commons BY license
  •   Request permissions

    A furosemide–isonicotinamide cocrystal: an investigation of properties and extensive structural disorder

    H. E. Kerr, L. K. Softley, K. Suresh, A. Nangia, P. Hodgkinson and I. R. Evans, CrystEngComm, 2015, 17, 6707
    DOI: 10.1039/C5CE01183C

    This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements