Six novel forms of carbamazepine (CBZ) were prepared and characterised by single crystal X-ray diffraction (SXD) and powder X-ray diffraction (PXRD). These were [CBZ(H)][Cl] form I, [CBZ(H)][Cl] form II, [CBZ(H)[Br] form I, [CBZ(H)][Br] form II, [CBZ(H)][Br].H₂O and CBZ₂.[H₃O][Cl].2H₂O. In five of these cases the in-situ generation of HX (where X=Cl or Br) in non-aqueous environment gave protonation at the oxygen atom of the amide group of CBZ. The sixth sample forms a hydronium chloride cocrystal with CBZ. Water from air is incorporated into the crystal structure of [CBZ(H)][Cl] which forms the CBZ hydronium chloride. Despite previous claims that non-aqueous conditions were necessary to protonate CBZ, work with aqueous acids resulted in the structural characterisation of seven new forms of CBZ. These were, [CBZ(H)][Cl].H₂O:[CBZ(H)][Cl], [CBZ(H)][Br].H₂O:[CBZ(H)][Br], CBZ.[H₅O₂]₀.₂₅[BF₄]₀.₂₅.H₂O, [CBZ(H)][C₂H₄S₂O₆], CBZ.[CBZ(H)][BF₄].H₂O, CBZ.[Acridinium][I₃][I₂]₂.₅ and CBZ₂[Acrdinium]₂[I₅][I₃].[I₂]₀.₅. In five cases products with CBZ protonated at the amide O atom were again observed. The two acridinium containing products contain only neutral CBZ but have added interest as acridine is a known metabolite of CBZ. It was shown that the protonated species can be differentiated from neutral CBZ phases as protonation is accompanied by lengthening of the C-O bond and shortening of the C-N bonds. The hydrogen bonding motifs present in the protonated species also differ from those typically observed in neutral CBZ forms. The first metal ion containing phases of CBZ were also synthesised and characterised by SXD. These were the sodium ion containing ionic cocrystal (ICC) species [Na(CBZ)₄(MeOH)][I].H₂O, [Na(CBZ)₅][I₃] and [Na(CBZ)₅][Acridinium][IBr₂]₂.
|Date of Award||13 May 2015|
- University Of Strathclyde
|Supervisor||Alan Kennedy (Supervisor) & John Reglinski (Supervisor)|