Counter-current Chromatography for the Purification of High Value Natural Compounds: Performance Modelling and Solvent Selection

Abstract

Counter-current chromatography (CCC) is a separation technique, which utilises two immiscible liquid phases in equilibrium as stationary and mobile phases. It emerged in the 1970s and had been primarily used in academia. Over the past few years its application in the pharmaceutical industry has increased as a high-throughput system. However, most businesses are still reluctant to use this technique due to the lack of understanding in solvent selection, which is essential for experimental design. Additionally, instrument design was a mainly empirical methodology, because there were no reliable models available that could predict the performance of a CCC column. One aim of this research project was to improve solvent system selection for CCC separations in order to facilitate the use of greener solvents. Therefore, a solubility driven approach for solvent selection from a list of preferred solvents was developed. This approach enables rapid solvent system selection, and potentially improves sample loading, because solvent systems are chosen by taking the solubility of target materials into account. Another aim of this PhD thesis was to develop a novel model that can predict the performance of a CCC column from column dimensions. That enables the prediction of a solute’s elution profile from a CCC column from scratch using instrument and operational parameters only. Unlike previously developed CCC models, the novel model does not resort to empirical calibration. This model was validated using a series of experimental results from literature and successfully predicted retention times as well as peak resolutions.