Separation of racemic chiral drugs using immobilized CHIRALPAK IA: methodology for preparative scale development

Abstract

Immobilized stationary phases represent a new perspective for analytical as well as preparative scale separation of chiral species. In this study, the basic data necessary for further development of the production-scale processes using CHIRALPAK IA columns were acquired. The new immobilized chiral stationary phase CHIRALPAK IA has proven to be useful for the chiral separations of propranolol, metoprolol, guaifenesin, and -Tetralol enantiomers. A broad range of standard and non-standard solvents used as components of mobile phases were tested and their influence on the separations was evaluated. A satisfactory separation considering further utilization of simulated moving bed chromatography was found for propranolol, guaifenesin, and -tetralol using the following mobile phases n-Heptane/methanol/ethanolamine (05/95/0.1, v/v/v), n-Heptane/ethanol (85/15, v/v) and n-Heptane/DCM (85/15, v/v), respectively. Inverse size exclusion chromatography was implemented to measure the porosity of the column using the set of polystyrene standards. The multicomponent adsorption equilibrium was characterized by linear + Langmuir model for -Tetralol and linear model for propranolol and guaifenesin due to their limited solubility in selected mobile phases. The isotherm model was successfully validated by comparison of pulse profiles obtained by solving the mathematical model and those obtained experimentally.