Salt and ionic cocrystalline forms of amides: protonation of carbamazepine in aqueous media

Amanda R. Buist, David S. Edgeley, Elena A. Kabova, Alan R. Kennedy, Debbie Hooper, David G. Rollo, Kenneth Shankland, Mark J. Spillman

Research output: Contribution to journalArticle

5 Citations (Scopus)
16 Downloads (Pure)

Abstract

The products of reactions of the pharmaceutical amide carbamazepine (CBZ) with strong acids under aqueous conditions were investigated by both powder and single crystal X-ray diffraction. Despite previous claims to the contrary, it was found that salt forms with CBZ protonated at the amide O atom could be isolated from reactions with both HCl and HBr. These forms include the newly identified hydrate phase [CBZ(H)][Cl].H2O. Reactions with other mineral acids (HI and HBF4) gave ionic cocrystalline (ICC) forms (CBZ.[acridinium][I3].2.5I2 and CBZ.[H5O2]0.25[BF4]0.25.H2O) as well as the salt form CBZ.[CBZ(H)][BF4].0.5H2O. Reaction of CBZ with a series of sulfonic acids also gave salt forms, namely [CBZ(H)][O3SC6H5], [CBZ(H)][O3SC6H4(OH)].0.5H2O, [CBZ(H)]2[O3SCH2CH2SO3] and [CBZ(H)][O3SC6H3(OH)(COOH)].H2O. CBZ and protonated CBZ(H) moieties can be differentiated in the solid state both by changes to molecular geometry and by differing packing preferences.
Original languageEnglish
Pages (from-to)5955-5962
Number of pages8
JournalCrystal Growth and Design
Volume15
Early online date28 Oct 2015
DOIs
Publication statusE-pub ahead of print - 28 Oct 2015

    Fingerprint

Keywords

  • carbamazepine
  • amides
  • crystal X-ray diffraction

Cite this

Buist, A. R., Edgeley, D. S., Kabova, E. A., Kennedy, A. R., Hooper, D., Rollo, D. G., ... Spillman, M. J. (2015). Salt and ionic cocrystalline forms of amides: protonation of carbamazepine in aqueous media. Crystal Growth and Design, 15, 5955-5962. https://doi.org/10.1021/acs.cgd.5b01223