Enantiomeric Resolution of Racemic Ibuprofen in Supercritical Carbon Dioxide Using a Chiral Resolving Agent

摘要

Given the inherent dangers associated with racemic pharmaceuticals, exhaustive investigations of techniques designed to separate enantiomers have been performed. Most methods are intrinsically expensive, consume vast quantities of organic solvent, and involve combinations of time consuming crystallization and/or chromatographic procedures. This dissertation reports herein the first step towards using pressure as a readily controllable variable during enantiomeric separation of racemic ibuprofen in liquid and supercritical carbon dioxide. Custom synthesized, CO2 soluble and partially soluble resolving agents are added to the fluid phase to promote formation of diastereomeric salt pairs, which exhibit differences in their chemical and physical properties, such as solubility. Unlike enantiomers, which exhibit nearly identical solubility in carbon dioxide, separation of salt pairs may be accomplished by selective extraction at designated pressures due to the differences in their phase behavior in CO2. Because formation of ion pair complexes occurs readily in media of low polarity, supercritical carbon dioxide offers an attractive alternative to traditional organic media.