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Simulated moving bed chromatography overview



SMB (Simulated Moving Bed) Background:

Simulated moving bed (SMB) technology is a chromatography technique that is traditionally used in oil and energy industry for recovery and purification of p-xylene and other aromatic components separated from naphtha feed.  After it became commercialized heavily into the oil industry, SMB technology made its mark on the food industry by separating fructose from glucose in a molasses feed.  Since then (1990s), SMB chromatography has become increasingly popular with biotechnology companies for purification and recovery of active pharmaceutical intermediates (APIs). Several examples of processes established in industry include the SORBEX® process as well as the PAREX®, and Aromax® for recovery of p-xylene from C-8 isomer mixtures both commercialized by UOP.  Other examples of SMB processes commercialized (also from UOP) include Ebex® for the separation of ethylbenzene from a mixture of C-8 aromatic isomers, Molex® for the separation of n-parafin’s from branched and cyclic hydrocarbons, and Olex® for the separation of olefins from parafins. Other examples in the chemical industry are Cresex® and Cymex® for the separation of p-cresol and p-cymene from its isomers and Sarex®.

To understand and utilize the SMB technology, it is imperative to study techniques of batch or column chromatography.  All research and development efforts to operate an SMB are focused on column chromatography studies.  Once components in a material are able to be separated at reasonable capacity with respect to a certain mobile phase, stationary phase, and feed flow rate, a scale up to SMB is possible.  Column chromatography, at any scale, is not practical to use for large scale production and purification of molecules.  Compared to SMB technology, in column chromatography, the stationary phase is not utilized efficiently.  This is because the separation zone between the components decreases during a column chromatography separation.  In an SMB, the separation zone is large and is maintained at a constant width.  Also, compounds are often unable to be separated in column chromatography because the column length is usually not long enough.  Overall, in column chromatography, the stationary phase is largely under-utilized and thus most column separation processes require excess amounts of solvent to complete a separation between compounds.  One of the major drawbacks of column chromatography is that it is a batch or linear process which results in the process having to be repeated to achieve a similar result as continuous SMB process.  Thus, a column chromatography separation is always expensive to scale up as compared to an SMB. 


Moving Bed Principle:

A hypothetical moving bed system and a liquid phase composition profile are shown in Figure 1. The adsorbent circulates continuously as a dense bed in a closed cycle and moves up the adsorbent chamber from bottom to top. Liquid streams flow down through the bed counter-currently to the solid. The feed is assumed to be a binary mixture of A and B, with component A being adsorbed selectively. Feed is introduced to the bed as shown.

Desorbent D is introduced to the bed at a higher level. This desorbent is a liquid of different boiling point from the feed components and can displace feed components from the pores. Conversely, feed components can displace desorbent from the pores with proper adjustment of relative flow rates of solid and liquid.

Raffinate product, consisting of the less strongly adsorbed component B mixed with desorbent, is withdrawn from a position below the feed entry. Only a portion of the liquid flowing in the bed is withdrawn at this point; the remainder continues to flow into the next section of the bed. Extract product, consisting of the more strongly adsorbed component A mixed with desorbent, is withdrawn from the bed; again, only a portion of the flowing liquid in the bed is withdrawn, and the remainder continues to flow into the next bed section.

The positions of introduction and withdrawal of net streams divide the bed into four zones, each of which performs a different function as described below.

Zone 1. The primary function of this zone is to adsorb A from the liquid.

Zone 2. The primary function of this zone is to remove B from the pores of the solid

Zone 3. The function of this zone is to desorb A from the pores

Zone 4. The purpose of this zone is to act as a buffer to prevent component B, which is at the bottom of

Zone 1, from passing into Zone 3, where it would contaminate extracted component A.


Simulated Moving Bed Operation

In the moving bed system of Figure 1, solid is moving continuously in a closed circuit past fixed points of introduction and withdrawal of liquid. The same results can be obtained by holding the bed stationary and periodically moving the positions at which the various streams enter and leave. A shift in the positions of the introduction of the liquid feed and the withdrawal in the direction of fluid flow through the bed simulate the movement of solid in the opposite direction.

Of course, moving the liquid feed and withdrawal positions continuously is impractical. However, approximately the same effect can be produced by providing multiple liquid access lines to the bed and periodically switching each stream to the adjacent line. Functionally, the adsorbent bed has no top or bottom and is equivalent to an annular bed. Therefore, the four liquid access positions can be moved around the bed continually, always maintaining the same distance between the various streams.

The commercial application of this concept is portrayed in Figure 2, 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 multi-port stopcock in directing each of several streams to different lines. At the right‑hand face of the valve, the four streams to and from the process is continuously fed and withdrawn. At the left‑hand face of the valve, a number of lines are connected that terminate in distributors within the adsorbent bed.  The rotary valve is the most widely used method in industrial scale applications for accomplishing the stepwise movement of external streams from bed to bed.  This same function can be accomplished using manifolds of on-off valves.  For a 24-bed process application, more than 100 such valves could be required.  Small scale SMB applications, such as for chiral separations, make extensive use of switching valves. 

At any particular moment, only four lines from the rotary valve to the adsorbent chamber are active. Figure 2 shows the flows at a time when lines 2, 5, 9, and 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 of line 2, extract is drawn from 6 instead of 5, feed enters 10 instead of 9, and raffinate is drawn from 1 instead of 12.

Figure 1 shows that in the moving bed operation, the liquid flow rate in each of the four zones is different because of the addition or withdrawal of the various streams. In the simulated moving‑bed of Figure 2, the liquid flow rate is controlled by the circulating pump. At the position shown in Figure 2, the pump is between the raffinate and desorbent ports, and therefore should be pumping at a rate appropriate for Zone 4. However, after the next switch in position of the rotary valve, the pump is between the feed and raffinate ports, and should therefore be pumping at a rate appropriate for Zone 1. Stated briefly, the circulating pump must be programmed to pump at four different rates. The control point is altered each time an external stream is transferred from line 12 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 operations. 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 variable at a fixed feed rate, as in the operation pictured in Figure 2, is the cycle time, which is measured by the time required for one complete rotation of the rotary valve (this rotation is the analog of adsorbent circulation rate in an actual moving bed system), and the liquid flow rate in Zones 2, 3, and 4. When these control variables are specified, all other net rates to and from the bed and the sequence of 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 effect on composition of the products has appeared. Various aspects of process control are described in the patent literature.





Work model and Capabilities:

  • Work model supports the process from discovery phase to lab scale and all the way to production scale
  • Orochem has capabilities of manufacturing customized adsorbents which can efficiently work on SMB process.
  • Orochem has a team of highly experienced people in the field of SMB – We have a team of chemists, Chemical and Mechanical Engineers working closely right from the discovery stage to the production stage


Cost Effectivness :
  • Orochem SMB large scale models are based on 300um and larger particle size thereby reducing the cost of the adsorbent and equipment.


Support and services:
  • Orochem provides full support for further process development and optimization even after installation of the process
  • Orochem provides full documentation and technical services required for cGMP applications
  • Orochem deligently works towards making the product most cost effective in the industry
  • Orochem has in house analytical equipment's like HPLC, GC, mass spec, FTIR, UHPLC etc.


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