Design of Multistage Counter-Current Liquid–Liquid Extraction for Small-Scale Applications

Abstract

Multistage counter-current liquid–liquid extraction (MCCE) is a common unit operation in the chemical industry, but the technique is often difficult to use at laboratory and small production scales, because most MCCE systems are gravity-driven and require a large volume (∼100 mL). We present a new MCCE design that integrates segmented flow mixing and membrane-based phase separators to achieve equilibrium extraction at each stage. Multichannel peristaltic pumps transfer fluids from stage to stage in a counter-current manner, rather than dedicated pumps at each stage. A self-tuning pressure control element incorporated into each separator allows robust operation, even in the presence of variation between stages and imprecise pumping. Experimental data from two classical ternary case studies (toluene–acetone–water and ethyl acetate–acetic acid–water) compare well to ASPEN Plus simulations, showing that the extraction efficiency is ∼100%, regardless of the number of stages. Finally, we demonstrate the efficiency of the small-scale MCCE system (∼2 mL/stage) with an industrial example of recovery of THF and ethyl acetate from methanol, ethanol, iso-butanol, and tert-butanol mixtures.

Continuous manufacturing – the Green Chemistry promise?

“…They have found widespread use in multistep reaction sequences. [121][122][123][124] These membrane units require some initial optimization dependent on the content of the reaction stream, as they exploit the difference in surface tension between the aqueous and organic phase, but once optimized, these systems offer a truly continuous methodology to complement the continuous flow synthesis of the API. 125 With minimal energy requirements and the use of cheap and disposable materials, the membrane-based phase separation is a robust and Green unit operation that takes a shift towards a fully continuous methodology for the purification and separation of API reaction streams (G1, G6).…”

Process modelling, design and technoeconomic Liquid–Liquid Extraction (LLE) optimisation for comparative evaluation of batch vs. continuous pharmaceutical manufacturing of atropine

“…Significant efforts in modelling and simulation in pursuit of continuous pharmaceutical separation process development have been demonstrated in recent years. Implementation of combined experimental and modelling approaches towards integrated LLE design in the literature for pharmaceutical purifications and separations demonstrate the utility of theoretical methods in establishing optimal design and operating parameters (Drageset and Bjørsvik, 2016;Monbaliu et al, 2016;Weeranoppanant et al, 2017). Mathematical optimisation can be used to identify cost optimal process designs for pharmaceutical manufacturing campaigns (Gross and Roosen, 1998;Patrascu and Barton, 2018); plantwide modelling and optimisation with a focus on optimal continuous separation process design towards total cost minimisation have been implemented by our group for numerous APIs (Jolliffe and Gerogiorgis, 2017a,b;Diab and Gerogiorgis, 2018b).…”

Smart Equipment – A Perspective Paper

“…This not only affects reactor development, but also miniaturized separation steps from distillation, extraction, or crystallization as well as miniaturized sensors. With novel products, membrane and adsorptive reactors optimized by volume and area will lead to integrated processes , on lab and pilot scale , .…”