OPTIMAL DESIGN OF A FOUR-ZONE SIMULATED MOVING BED PROCESS FOR SEPARATION OF HOMOHARRINGTONINE AND HARRINGTONINE

Abstract

A simulated moving bed (SMB) technology was applied to the separation of homoharringtonine (HHT) and harringtonine (HT), which were known to have the potentiality of being used as anti-cancer agents. First, a series of pulse injection experiments were performed for estimation of the adsorption isotherm and mass-transfer parameters of HHT and HT. The estimated parameters were utilised in the SMB optimisation tool based on the standing wave design method. From the optimisation tool prepared, the SMB operating parameters (zone flow rates and step time) that led to the highest throughput were obtained under the constraints of product purities (=99.0%) and pressure drop (<= 1000 psi). Such an optimisation work was then extended to determine an optimal size of the adsorbent particle for the SMB of interest. The results showed that a particle size of 29 mu m was the optimal one for maximising the SMB throughput under the conditions that the column configuration was 2-2-2-2 and the length of each column was 25 cm. If the SMB had the particle size other than 29 mu m, its throughput was limited by either the maximum operating pressure or the mass-transfer efficiency. Finally, an efficient procedure of removing a mobile-phase additive (ammonium formate) from the product stream of the aforementioned SMB system was developed using a liquid-liquid extraction (LLE) technique. From the results of this study, it was confirmed that the SMB process coupled with a LLE procedure could be highly effective in separating HHT and HT with high throughout and high purity.