Supercritical fluid chromatography (SFC) is being increasingly used for small and medium scale chiral separations that are chiefly encountered during the drug development process. This technique is particularly attractive as it is possible to access enantiopure substances in a short time while enormously reducing organic solvent consumption. The retention of a solute in SFC depends on several operating parameters, including temperature, pressure, modifier type and concentration. These parameters give additional degrees of freedom to design the separation.

This study reports the separations of the enantiomers of a key anti-inflammatory drug flurbiprofen. Two stationary phases, namely, Chiralcel OD-H and Chiralpak AD-H were screened for possible stationary phases. Chiralpak-AD-H showed better separation performance and was hence chosen for further study. The effect of key operating parameters namely pressure, modifier type and concentration on the henry constant were studied at an analytical scale and were modeled. Overloaded injections were performed to measure the non-linear adsorption isotherm parameters. A competitive Langmuir isotherm was found to describe the elution profiles well and its parameters were estimated using a systematic approach by comparing the elution profiles with the simulated ones. Key performance parameters such as productivity and solvent consumption were calculated using numerical simulations and were compared with experiments. Further, using the triangle theory, the productivity of a supercritical fluid-simulated moving bed chromatography (SF-SMB) process was estimated.