Chromatographic separation of binary and ternary mixtures by Three Columns Intermittent Simulated Moving Bed (3C-ISMB)

Simulated Moving Bed (SMB) is a multi-column chromatographic process, which allows the continuous separation of chemical and biological compounds for the purposes of preparative chromatography. Patented in the early 60s, it finds its first application in the petrochemical industry for the recovery of high pure n-paraffins. However, starting from the 90s, also pharmaceutical companies demonstrated their interest on the SMB technology a cause of the economical importance that gained the separation of racemic mixtures for isolation of highly pure active pharmaceutical ingredients (API). Furthermore, an intense research activity in the chiral resolution, it is demonstrated by the yearly awarded patents and publications at that time. Considering the fact that downstream processing costs can reach 70% to 90% of the total production costs of a drug, may enforce pharmaceutical companies to adapt their plants with chromatographic separation processes, which can deliver superior separation performances compared to the classical batch chromatography, which is the most used separation technique in the industry so far. As a matter of fact, the cost-efficient advantages offered by continuous processes make SMB to find nowadays several areas of application such as fine chemistry, biotechnology and food processing, although limited to binary separations. Recently, a continual development of SMB processes has broken this limitation extending its application on the separation of ternary mixtures, where the major focus relies in the challenging task of recovering the intermediate component. Beside the high purity that SMB processes can achieve by the resolution of species with very low selectivity, the productivity of the process is the most important performance indicator for evident economic reasons. In this regard, a modification of the conventional process, named ”Intermittent Simulated Moving Bed” (I-SMB) demonstrates (in 2010) superior productivity when compared to the standard SMB. Furthermore, its ”intermittent” mode of operation, i.e. the semi continuous feeding permits to countercurrent undesired dispersion effects which affect the purity levels when the conventional SMB is operated at ”optimized” conditions. In the frame of this master thesis, a new SMB process was developed: the Three Columns Intermittent Simulated Moving Bed (3C-ISMB). Especially, when the 3C-ISMB process is compared with its ”Four Columns counterpart” (the I-SMB in 1-1-1-1 configuration, which was renamed in this work as ”4C-ISMB”), three things could be demonstrated: first, same purity levels by both ISMB processes at the same operating parameters. Second, a superior productivity of 33% at the same operating conditions by simply reducing the number of columns from four to three. More important, these ISMB processes were compared at their optimal operation, i.e. when the maximal allowable pressure drop was fully exploited. In this regard, binary separations at nonlinear chromatographic conditions were performed at different feed concentrations, separating a thermodynamically well known system, the racemic mixture (±)-Tröger’s Base on a laboratory-scale plant. Before implementing the ISMB processes, operating points were designed near to the optimum in order to achieve the highest possible productivity but still having complete separation. In particular, the design work could be accomplished with the Triangle Theory, an extremely useful and