Simulated moving bed operation

Simulated Moving Bed (SMB) chromatography is a continuous method o f separation in which the sample is continuously injected and two product streams are continuously collected. SMB is thus a binary separation technique in which the original sample is split into two parts, the two product streams. If the sample contains many components, generally the component o f interest is collected in one o f the product streams, and all the other components are collected together in the other stream. If the sample contains only two components, as in chiral separations, each component can be collected in essentially pure form. The elution profile can be held in place if the stationary phase moves in one direction and the mobile phase moves in the other direction (fig 20) {Gattuso, 199^).

Solid 4-D Desorbent D Desorption o f A Extract A + D Desorption o f B Feed A + B Adsorption o f A RefGnate B+ D Partial desorption o fD \t a ► = Flow o f liquid = Flow o f solid

M obile p h a s e !

flow "

Balance

^ I Stationary phase

Synthetic routes to single enantiomer drugs Stationary and m obile phase in motion

Figure 20: Simulated moving bed technology

If the feed is continuously introduced at the midpoint of the column, the concentration profile can be maintained, and the bands are spread out over the entire column. Although the profiles are only partially resolved, high purity products can be collected at either end (fig 21) {Gattuso, 1996).

For practical purposes, maintaining the movement of the stationary phase is difficult. If the movement o f the stationary phase is stopped, the profile moves around the column, and the feed and withdrawal points are no longer in the correct position. To compensate, the feed and withdrawal points must be moved continuously, or indexed, to keep up with the profile. To avoid moving the feed and withdrawal points continuously, the feed and withdrawal points are indexed at discrete points. For ease o f operation, the column is divided into sections, which consist of a number of individual columns arranged in series (fig 22). Now if the injection and collection points are regularly changed, the net result is the same as it would be if the stationary phase was moving. The number of column beds within each section and the total number o f columns are adjustable.

M obile phasd A

flow I—* — i- Strongly adsorbed

product Removal o f

product

Start feed Feed

Removal o f product Stationary phase flow

Weakly adsorbed product

Figure 21: Continuous introduction of the feed in the midpoint of the simulated moving bed column

Cyclic Column Short columns in series

Time 2 Flow liquid Time Time 1 A + B Time Time A + B Solid displacemem

The commercial application of simulated moving bed is portrayed in fig 23, which shows the adsorbent as a stationary bed. A liquid circulating pump is provided to pump liquid from the bottom outlet to the top inlet of the adsorbent chamber. A fluid directing device known as a rotary valve is provided. The rotary valve functions on the same principle as a multiport stopcock in directing each o f several streams to different lines. At the right hand face of the valve, the four streams to and from the process are continuously fed and withdrawn. At the left hand face of the valve, a number o f lines are coimected that terminate in distributors within the adsorbent bed

(Gembicki, 1991).

At any particular moment, only four lines from the rotary valve to the adsorbent chamber are active. Fig 23 shows the flow at a time when lines 2, 5,9, 12 are active. When the rotating element of the rotary valve is moved to its next position, each net flow is transferred to the adjacent line; thus, desorbent enters line 3 instead o f line 2, extract is drawn from 6 instead of 5, feed enters 10 instead of 9, and raffinate is drawn from 1 instead of 1 2.

In the moving bed (fig 19) operation, the liquid flow rate in each o f the four zones is different because of the addition or the withdrawal of the various steams. In the simulated moving bed (Fig 23), the liquid flow rate is controlled by the circulating pump. The pump is between the raffinate and desorbent ports, and therefore should be pumping at a flow rate appropriate for zone 4. However, after the next switch in position of the rotary valve, the pump is between the feed and the raffinate ports, and should therefore be pumping at the rate appropriate for zone 1. The circulating pump must be programmed to pump at four different rates. The controlled point is altered each time an external stream is transferred from line 1 2 to line 1.

To complete the simulation, the liquid flow rate relative to the solid must be the same in both the moving bed and simulated moving bed. Because the solid is physically stationary in the simulated moving bed operation, the liquid velocity relative to the vessel wall must be higher than in an actual moving bed operation.

The primary control variables at a fixed rate (fig 23), are the cycle time, which is measured by the time required for one complete rotation of the rotary valve (this rotation is the analogue of adsorbent circulation rate in an actual moving bed system), and the liquid flow rate in zones 2 , 3 , 4 . When these control variables are specified, all other net rates to and from the bed and the sequence o f rates required at the liquid circulating pump are fixed. An analysis of sequential samples taken at the liquid circulating pump can trace the composition profile in the entire bed. This profile provides a guide to any changes in flow rates required to maintain proper performance before any significant effects on composition of the products has appeared {Genbicki, 1991).

Temperature and pressure are not considered as primary operating variables: the temperature is set sufficiently high to achieve rapid mass transfer rates, and the pressure is sufficiently high to avoid vaporisation. In liquid phase operation, as contrasted to vapour-phase operation, the required bed temperature bears no relation to the boiling range of the feed, an advantage when heat sensitive stocks are being tested {Genbicki, 1991).