Structural Studies of the Polymorphs of Carbamazepine, Its Dihydrate, and Two Solvates

High-field cross-polarisation magic-angle spinning 13C NMR
spectra are presented for the four known polymorphs of
anhydrous carbamazepine, for a dihydrate, and for two solvates.
These are all distinctive, despite relatively low spectral dispersion, and give immediate information about the crystallographic
asymmetric unit. The results for the trigonal and the two
monoclinic forms are consistent with the published crystal
structures. That of the triclinic form was found to contain four
molecules in the crystallographic asymmetric unit, which has
recently been confirmed by an X-ray diffraction study. NMR
shows that the dihydrate has one molecule in the asymmetric
unit, and the full crystal structure derived from single-crystal
X-ray diffraction work is reported herein. It is found to be
ordered and monoclinic, in contrast to the reported disordered
orthorhombic structure. The discrepancy is attributed to the
common occurrence of multiple micro-twinning. Shielding
computations using a method which takes explicit account of
the repetition inherent in a crystal lattice are reported for the
P-monoclinic form and are compared to the experimental
chemical shifts. The NMR data of all the forms are discussed
in relation to variations in the molecular geometry of the
hydrogen-bonded dimers (except in the case of two solvates).
Chemical shift variations are explored as a function of the amide
torsion using the Gaussian computer program.