Salt and Ionic Cocrystalline Forms of Amides: Protonation of Carbamazepine in Aqueous Media.

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• 作者：Amanda R. Buist ; David S. Edgeley ; Elena A. Kabova ; Alan R. Kennedy ; Debbie Hooper ; David G. Rollo ; Kenneth Shankland ; Mark J. Spillman
• 刊名：Crystal Growth & Design
• 出版年：2015
• 出版时间：December 2, 2015
• 年：2015
• 卷：15
• 期：12
• 页码：5955-5962
• 全文大小：367K
• ISSN：1528-7505

文摘

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]路H₂O. Reactions with other mineral acids (HI and HBF₄) gave ionic cocrystalline (ICC) forms (CBZ路[acridinium][I₃]路2.5I₂ and CBZ路[H₅O₂]_0.25[BF₄]_0.25路H₂O) as well as the salt form CBZ路[CBZ(H)][BF₄]路0.5H₂O. Reaction of CBZ with a series of sulfonic acids also gave salt forms, namely, [CBZ(H)][O₃SC₆H₅], [CBZ(H)][O₃SC₆H₄(OH)]路0.5H₂O, [CBZ(H)]₂[O₃SCH₂CH₂SO₃], and [CBZ(H)][O₃SC₆H₃(OH) (COOH)]路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.