Preparative chiral separations by supercritical fluid chromatography

The overall objective of the project was to develop methods for the rational design of supercritical fluid chromatographic(SFC) processes. There were two significant outcomes of this project: 1. Rational design methodology for SFC separations. 2. A new method for the determination of competitive Langmuir isotherm parameters. The separation of the enantiomers of flurbiprofen on an amylose-derived chiral stationary phase, Chiralpak AD-H, by supercritical fluid chromatography under both linear and nonlinear conditions is studied. Pulse injections were implemented using supercritical CO2 modified with methanol as a mobile phase at a temperature of 30◦C. At linear conditions, the isotherm is determined directly from the chromatogram. Under overload conditions, the elution profiles were described by competitive Langmuir and bi-Langmuir isotherm. Isotherm parameters were estimated using the inverse method and the effects of operation variables such as pressure and modifier composition were studied. Optimization algorithms were developed to arrive at conditions to maximize the process performance. Both isocratic and modifier gradient operations were studied.It was shown that by the use of these advanced methods effective separations can be designed and significant improvement in productivity with concurrent reduction in organic solvent consumption can be achieved. These results that show the superior performance of the SFC were experimentally validated.RG 38/0