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.

Resolution of N-methylamphetamine enantiomers with tartaric acid derivatives by supercritical fluid extraction

“…Diastereomeric salts were formed under supercritical conditions using the solution enhanced dispersion by supercritical fluids (SEDS) technique. 12 Over the last 10 years, several racemic organic acids, 13 bases 14;15 and alcohols 16 have been resolved by SFE in our laboratory. In many cases the extraction pressure (P ) or/and extraction temperature (T ) strongly influenced the efficiency of the resolution.…”

Gas Antisolvent Approach for the Precipitation of α-Methoxyphenylacetic Acid – (R)-1-Cyclohexylethylamine Diateromeric Salt

“…While several chiral catalytic processes are already industrialized, the conventional manufacturing technique mainly includes diastereomeric salt formation followed by fractionated crystallization. [1][2][3][4] These techniques highly depend on reaction conditions such as slight changes in temperature, pressure, etc. Hence, each reaction parameter needs careful optimisation.…”

Determination, correlation and prediction of the solubilities of niflumic acid, clofenamic acid and tolfenamic acid in supercritical CO2

“…In pharmaceutical industry, sc-CO 2 attracts more attention because it is a non-toxic solvent without solvent residual and can be used to treat the heat-sensitive intermediates and active pharmaceutical ingredients (APIs). It can be used as solvent in processing APIs such as synthesis, separation and micronization [5][6][7].…”