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 journalArticlepeer-review

6 Citations (Scopus)
27 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

Keywords

  • carbamazepine
  • amides
  • crystal X-ray diffraction

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