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Crystallization of pure anhydrous polymorphs of carbamazepine by solution enhanced dispersion with supercritical
A D Edwards1, B Y Shekunov, A Kordikowski
1Drug Delivery Group, School of Pharmacy, University of Bradford, BD7 1DP, United Kingdom.
Abstract:
Pure anhydrous polymorphs of carbamazepine were prepared by solution-enhanced dispersion with supercritical fluids (SEDS). Crystallization of the polymorphs was studied. Mechanisms are proposed that consider the thermodynamics of carbamazepine, supersaturation in the SEDS process, and the binary phase equilibria of organic solvents and the carbon dioxide antisolvent. alpha-Carbamazepine was crystallized at high supersaturations and low temperatures, beta-carbamazepine crystallized from a methanol-carbon dioxide phase split, and gamma-carbamazepine crystallized via nucleation at high temperatures and low supersaturation.