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

Buist, A. R., Edgeley, D. S., Kabova, E. A., Kennedy, A. R., Hooper, D., Rollo, D. G., Shankland, K. and Spillman, M. J. (2015) Salt and ionic cocrystalline forms of amides: protonation of carbamazepine in aqueous media. Crystal Growth & Design, 15 (12). pp. 5955-5962. ISSN 1528-7483 doi: 10.1021/acs.cgd.5b01223

Abstract/Summary

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]·H O. Reactions with other mineral acids (HI and HBF ) gave ionic cocrystalline (ICC) forms (CBZ· [acridinium][I ]·2.5I and CBZ·[H O ] [BF ] ·H O) as well as the salt form CBZ·[CBZ(H)][BF ]·0.5H O. Reaction 2 4 3 2 5 2 0.25 4 0.25 2 4 2 of CBZ with a series of sulfonic acids also gave salt forms, namely, [CBZ(H)][O SC H ], [CBZ(H)][O SC H (OH)]· 3 6 5 3 6 4 0.5H O, [CBZ(H)] [O SCH CH SO ], and [CBZ(H)][O SC H (OH) (COOH)]·H O. CBZ and protonated CBZ(H) 2 2 3 2 2 3 3 6 3 2 moieties can be differentiated in the solid state both by changes to molecular geometry and by differing packing preferences

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/48596
Identification Number/DOI	10.1021/acs.cgd.5b01223
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Chemical Analysis Facility (CAF) > Xray (CAF) Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Pharmaceutics Research Group
Publisher	American Chemical Society
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