Crystal polymorphism in a carbamazepine derivative: oxcarbazepine.

Although crystal polymorphism of carbamazepine (CBZ), an anticonvulsant used to treat epilepsy, has been known for decades, the phenomenon has only recently been noted for its keto-derivative oxcarbazepine (OCB). Here it is demonstrated that OCB possesses at least three anhydrous polymorphs. Although all forms are morphologically similar, making differentiation between crystal modifications by optical microscopy difficult, powder X-ray diffraction, Raman spectroscopy, and thermomicroscopy show distinctive differences. These techniques provide an efficient method of distinguishing between the three polymorphs. The crystal structure of form II of OCB is reported for the first time and the structure of form I has been redetermined at low temperature. Remarkably, both the molecular conformation and crystal packing of form II are in excellent agreement with the blind prediction made in 2007. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association.