Resolution in CCC: The Effect of Operating Conditions and Phase System Properties on Scale‐Up

Abstract

Being able to accurately predict the eluted volume of a substance with a known distribution ratio will depend on accurately knowing the retention volume of the stationary phase. Sample resolution depends on a number of factors that are not so easy to predict: the properties of the phase systems, the number of mixing and settling cycles per unit time, the rate of mass transfer during mixing, and the quality of mixing between the phase systems. The extent of mixing between the phases will, in turn, depend on the flow rate of the mobile phase and the “g” field acting across the stratified phases within the coiled tubing. A systematic study is made of how sample resolution changes with the key operating variables associated with scale‐up: the mobile phase flow, the bore of the tubing, and the rotational speed. It shows how the commonly accepted characteristic, good resolution at low flow and poor resolution at high flow, slowly changes as tubing bore increases to one of poor resolution at low flow rising to optimum resolution at high flow and a slow decline in resolution at very high flow. Furthermore, it goes on to show that, as phase system physical properties change when moving from hydrophobic phase systems to more polar hydrophilic ones, the optimum resolution remains in a similar speed and flow range. It also shows that the key variable for scale‐up, the throughput of sample in kg/hour, increases significantly as mobile phase flow increases, provided the rotational speeds are high enough. Optimum throughput has not yet been reached, which is extremely promising for realising process scale CCC.

Keywords:

• Countercurrent chromatography
• Resolution
• Scaling‐up
• Throughput
• Flow rate effects
• Tubing bore effects

Acknowledgments

This research and the development of the IMI experimental bobbins was carried out with grant support from the EPSRC No. GR/R03143/01, “Realising Process Scale Countercurrent Chromatography.” R. van den Heuvel was partly supported by Leonardo on an industrial placement and partly by Romulus Technology (Space) Ltd.