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

4 Citations (Scopus)

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.
LanguageEnglish
Pages5955-5962
Number of pages8
JournalCrystal Growth and Design
Volume15
Early online date28 Oct 2015
DOIs
Publication statusE-pub ahead of print - 28 Oct 2015

Fingerprint

Protonation
Carbamazepine
Amides
amides
Salts
salts
Acids
Hydrates
Drug products
acids
sulfonic acid
Minerals
Single crystals
hydrates
Powders
X ray diffraction
Atoms
Geometry
minerals
solid state

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
Buist, Amanda R. ; Edgeley, David S. ; Kabova, Elena A. ; Kennedy, Alan R. ; Hooper, Debbie ; Rollo, David G. ; Shankland, Kenneth ; Spillman, Mark J. / Salt and ionic cocrystalline forms of amides : protonation of carbamazepine in aqueous media. In: Crystal Growth and Design. 2015 ; Vol. 15. pp. 5955-5962.
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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.",
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Buist, AR, Edgeley, DS, Kabova, EA, Kennedy, AR, Hooper, D, Rollo, DG, Shankland, K & Spillman, MJ 2015, 'Salt and ionic cocrystalline forms of amides: protonation of carbamazepine in aqueous media' Crystal Growth and Design, vol. 15, pp. 5955-5962. https://doi.org/10.1021/acs.cgd.5b01223

Salt and ionic cocrystalline forms of amides : protonation of carbamazepine in aqueous media. / Buist, Amanda R.; Edgeley, David S.; Kabova, Elena A.; Kennedy, Alan R.; Hooper, Debbie; Rollo, David G.; Shankland, Kenneth; Spillman, Mark J.

In: Crystal Growth and Design, Vol. 15, 28.10.2015, p. 5955-5962.

Research output: Contribution to journalArticle

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T1 - Salt and ionic cocrystalline forms of amides

T2 - Crystal Growth and Design

AU - Buist, Amanda R.

AU - Edgeley, David S.

AU - Kabova, Elena A.

AU - Kennedy, Alan R.

AU - Hooper, Debbie

AU - Rollo, David G.

AU - Shankland, Kenneth

AU - Spillman, Mark J.

N1 - This document is the unedited author's version of a Submitted Work that was subsequently accepted for publication in Crystal Growth and Design, copyright © American Chemical Society after peer review. To access the final edited and published work, see http://www.dx.doi.org/10.1021/acs.cgd.5b01223 .

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Y1 - 2015/10/28

N2 - 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.

AB - 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.

KW - carbamazepine

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KW - crystal X-ray diffraction

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