Crystallization of pure anhydrous polymorphs of carbamazepine by solution enhanced dispersion with supercritical fluids (SEDS™)

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. α‐Carbamazepine was crystallized at high supersaturations and low temperatures, β‐carbamazepine crystallized from a methanol–carbon dioxide phase split, and γ‐carbamazepine crystallized via nucleation at high temperatures and low supersaturation. © 2001 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1115–1124, 2001