Resolution of ephedrine in supercritical CO2: A novel technique for the separation of chiral drugs

Abstract
Racemic ephedrine has been resolved by diastereomeric salt formation with mandelic acid using supercritical CO(2) as precipitating agent. Crystallizations were performed using the Solution Enhanced Dispersion by Supercritical Fluids (SEDS) technique. Temperature was varied between 35 and 75 degrees C, and pressures ranged from 100 to 350 bar. Resolution, determined by chiral capillary electrophoresis, is described as a function of temperature and density of the supercritical fluid. A comparison of SEDS-produced material with a conventional resolution method shows that SEDS-crystallized material exhibits identical properties to conventionally crystallized material.