Carbamazepine polymorph nucleation

The induction times of carbamazepine polymorphs [monoclinic, CBZ(M) and trigonal, CBZ(Trg)] were evaluated by optical microscopy. The polymorphs were identified by their crystal morphology where CBZ(M) crystallizes as prismatic crystals and CBZ(Trg) crystallizes as needles, which were confirmed by X-ray powder diffraction. It was determined that under constant supersaturation concomitant crystallization is favored in solvents that accept and donate hydrogen bonds (ethanol, methanol, isopropanol, etc.). However, the metastable CBZ(Trg) polymorph preferentially crystallized in solvents that primarily accept hydrogen bonds (ethyl acetate, methyl acetate, 2-butanone, etc.) with the stable CBZ(M) polymorph crystallizing at least an hour later. The induction times of CBZ polymorphs did not decrease with increases in solubility, suggesting that nucleation is not controlled by solubility differences. It was determined that CBZ polymorph nucleation was governed by the specific solute-solvent interactions that occurred in solution to... 

Kelly, R. Rodriguez-Hornedo, N. Solvent dependent nucleation and phase transformation of carbamazepine anhydrous polymorphs. 2006 (In preparation for submission). 

Murphy, D. The Solvent-Mediated Phase Transformation of Carbamazepine and the Influence of Surfactants on the 153. Nucleation Mechanism and Crystal Morphology. Ph.D. thesis. The University of Michigan Ann Arbor, MI, 1997. Rodriguez-Homedo, N. Murphy, D. Surfactant-facihtated crystallization of dihydrate carlramazepine during dissolution of anhydrous polymorph. J. Pharm. Sci. 2004, 95 (2),... 

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