Intermittent counter-current extraction a new continuous dynamic liquid-liquid extraction methodology

Abstract

For the pharmaceutical industry, the manufacture of high value pharmaceuticals from natural products, chemical synthetic routes or fermentation processes all require intensive downstream processing steps to produce a pure final product. A small footprint liquid-liquid processing method would help to reduce the capital cost and process development time of this downstream processing. In this thesis, it is hypothesised that continuous liquid-liquid extraction can be achieved using a standard hydrodynamic counter-current chromatography (CCC) instrument by switching the flow of the liquid phases between normal phase and reversed phase intermittently, so separating a feed stream into two eluant flows. A model of the process was derived and tested on three scales of instrument, from the semipreparative to the pilot scale. The method developed, Intermittent Counter-current Extraction (ICcE) was compared to dual-flow counter-current chromatography (DFCCC), the classical method of applying continuous extraction using a counter-current chromatograph. ICcE was found to be advantaged due to the more stable phase volume ratio achievable in the columns and the ability to operate the procedure on standard commercial twin-column CCC instruments which operate at high g-field. The robustness of the ICcE method was successfully demonstrated across a range of phase system polarities and at high throughput (1kg/day on a preparative instrument) with model mixtures of pharmaceutical compounds. The effectiveness of this new processing method was confirmed on three industrially relevant case studies. Firstly a polar extract from natural senna pods to extract important sennosides, secondly an intermediate polarity highly complex active pharmaceutical ingredient waste stream to recover the main active component and thirdly a non-polar natural product extract to recover macrocarpal compounds. In summary, the ICcE method now offers another tool in the range of liquid-liquid separation methods available to the pharmaceutical and other high value industries.