SIMULATED MOVING BED

CHROMATOGRAPHY

INTRODUCTION

Simulated moving bed chromatography (SMBC) was invented in the

1950s by Broughton and colleagues at UOP for large-scale separation of nparaffins , and is used today in many variations in the petrochemical, food,
and pharmaceutical industries. This enhanced productivity (up to 20-fold) is
achieved through much more efficient utilization of the solid and liquid
phases required for separation. In simplest terms, SMBC does more with
less.

INTRODUCTION

The basic concept of simulated moving bed chromatography is to use

multiple smaller columns containing the solid adsorbent (beds) rather than
one large column, and to move the beds in the opposite direction of the
fluid to achieve a counter current flow, rather than flowing fluids through one
static bed. The simulated movement is typically carried out through
multiport valves used between the columns, such that the input and output
fluid streams can be periodically switched from column to column in the
direction of fluid flow.

WHAT IS SMBC

In manufacturing, the simulated moving bed (SMB) process is a highly

engineered process for implementing chromatographic separation. It is used
to separate one chemical compound or one class of chemical compounds
from one or more other chemical compounds to provide significant quantities
of the purified or enriched material at a lower cost than could be obtained
using simple (batch) chromatography. It cannot provide any separation or
purification that cannot be done by a simple column purification.

In the simulated moving bed technique instead of moving the bed, the feed
inlet, the solvent or eluent inlet and the desired product exit and undesired
product exit positions are moved continuously. giving the impression of a
moving bed, with continuous flow of solid particles

WHAT IS SMBC

Production of large quantities of highly purified material at a dramatically

reduced cost. The cost reductions come about as a result of: the use of a
smaller amount of chromatographic separation media or stationary phase, a
continuous and high rate of production, and decreased solvent and energy
requirements.

This improved economic performance is brought about by a valve-andcolumn arrangement that is used to lengthen the stationary phase
indefinitely and allow very high solute loadings to the process.

ADVANTAGES OF SMBC

SMB provides lower production cost by requiring less column volume, less
chromatographic separation media ("packing" or "stationary phase"), using
less solvent and less energy, and requiring far less labour .

At industrial scale an SMB chromatographic separator is operated

continuously, requiring less resin and less solvent than batch
chromatography. The continuous operation facilitates operation control
and integration into production plants. Low eluent consumption High
product concentration High productivity Continuous process This system is
useful in the supercritical fluid extraction to obtain large quantity of specific
product.

DISADVANTAGES OF SMBC

Higher investment cost compared to single column operations

A higher complexity, as well as higher maintenance costs.

For purifications, in particular the isolation of an intermediate single

component or a fraction out of a multicomponent mixture, the SMB is not as
ideally suited. Normally, a single SMB will separate only two fractions from
each other, but a series or "train" of SMBs can perform multiple cuts and
purify one or more products from a multi-component mixture.

It is not readily suited for solvent gradients because this kind of purification
may be preferred for the purification of some biomolecules. A continuous
chromatography technique to overcome the two fraction limit and to apply
gradients is multicolumn counter current solvent gradient purification.

BASIC PRINCIPLE OF SMB

The basic idea of a moving-bed system is to promote a counter current

contact between the solid and the liquid phases.

Here the solid phase and liquid phase(solvent) moves opposite in the
direction.

Feed containing components say A and B is injected at the middle of the

column and solvent at the bottom of the column

Solid phase is moved at a velocity halfway between the velocity of A and B.

This will cause one component to move upward and another to move
downward ,leading thus to separation.

WORKING OF SMB

The classical moving bed column consists of four different zones .

Zone 1: The more retained product must be completely desorbed.

Zone 2:The less retained product must be completely desorbed.

Zone 3:The more retained product must be completely adsorbed.

Zone 4:The less retained product must be completely adsobed.

WORKING OF SMB
Practically counter current operation is achieved by using several fixed bed

column in series .The solids does not actually moves ,its flow is only
simulated by shifting inlet and outlet lines. So this simulated solid flow rate
downward is directly linked to shift period.
The flow rates must be chosen to stabilise the B(more retained product) front

between zones 1 and zone 2 and the A front between zones 3 and 4, and to
allow separation between zones 2 and 3.
Liquid and feed moves in the same direction and solid phase in opposite

direction.
.

SCHEMATIC DIAGRAM OF SMB

WORKING OF SMB

WORKING OF SMB

The simulated movement is carried out through the multiport valves.

Advantage of this zone scheme is:

The system is extremely compact , requiring minimum amount of solids and

eluent.

The process is continuous

APPLICATION OF SMB

Separation of sugars

Desalting

Purification of proteins and complex molecules

Separation of ionic molecules(production of lysine)

Separation in organic molecules

Separation of enantiomers of chiral compounds

Purification of antibodies

SEPARATION OF SUGARS

The separation is performed on polystyrene cation exchange resins in

calcium form, using warm water as the eluent.

The fructose forms a complex with the calcium ions and is retarded

The glucose and other oligosaccharides are eluted with the eluent

90 to 94% pure fructose was obtained.

The glucose rich fraction is about 80%

SMB packed with cationic resins in calcium form have also been used to
obtain other monosaccharides such as xylose or arabinose.

SEPARATION OF OPTICAL ISOMERS

SMB has received attention for chiral separations since early 1990s and is
today, considered as a cost-effective purification technology and common
to tool for separating isomers at production scale

Both high purity (>99 per cent) and high yield (>99 per cent) were achieved
experimentally using an SMB with a pressure limit of 2.4 Mpa.

Different enantiomers of a chiral drug molecule bind differently (or not at

all) to target receptors.

SMB Chromatography is widely used for separation of enantiomers

SEPARATION OF ENANTIOMERS IBUPROFEN

Ibuprofen is an antiflammatory agent with antipyretic and analgesic

properties.

Ibuprofen has a chiral centre and therefore exists as S(+) and R(-)
enantiomers.

Pharmacological activity of S(+) is 100 times higher than that of R(-)

enantiomer.

SBC is performed by SFC on chiral stationary phase and 4.5 mass%

propanol in C02 as mobile phase at a medium pressure of 15MPa.

Column diameter is 3cm and column length is 9.6cm.

Purity of 99% S(+) enantiomers of ibuprofen was obtained

SEPARATION OF ORGANIC MOLECULES

Many separations of organic molecules have been performed with the SMB
technology perform the separation of fatty acids like separation of EPA and
DHA from fish oil.

The separation of the phytol isomers is performed on classical silica

(Lichroprep Si 60, 25-40 micro metre) with an eluent made of heptane-ethyl
acetate (75-25 v/v) at 27C. This separation is implemented on a LICOSEP
8-200 (NOVASEP) which includes eight axial compression columns of 200
mm i.d. and up to 400 mm long. For this particular case, the columns were
packed with 3 kg of silica, leading to a column length of 17.7 cm (0.6%)

SEPARATION OF ORGANIC MOLECULES

Each outlet (extract and raffinate) was processed using a falling film
evaporator consisting of one to twelve 3 m tubes of 10 mm i.d. For this
separation, the pressure was set to 180 mbar, and the oil temperature to
80C. The concentrated extract and raffinate were recovered in 50 litre glass
vessels. We get extract purity of 98.4% and to a raffinate purity of 99.4%.

SEPARATION OF BUTANEDIOL AND PROPANEDIOL

Mitsubishi SP70 is used as the adsorbent for the SMB to separate BDO and PDO.

Mitsubishi SP70 is an FDA approved resin with easier desorption.

The adsorption isotherms, the axial dispersions, and the mass transfer coefficients
for BDO and PDO in packed columns with SP70 resin were investigated and
confirmed by fitting the experimental results to the prediction by ASPEN
simulation.

The SMB has four sections, and each has two columns.

Section 1 is the regeneration section for the adsorbent

Section 2 is the desorption section

Section 3 is the adsorption section and

Section 4 is the regeneration section for the desorbent.

SEPARATION OF BDO AND PDO

The liquid effluent from the fourth section is recycled to the first section, and the
recycling design is called a closed-loop design.

The liquid flow rate in each section of the SMB is controlled by four HPLC
pumps installed at ports of desorbent, feed, extract, and recycle. The movement
of the solid is fulfilled by constantly switching the ports of inlets and outlets to the
next column, and the flow rate of the solid can be controlled by setting the time
period for switching the ports.

Retention times for PDO and BDO are 2.05 and 3.45 min.

Eight PVC columns packed with SP70 for the SMB are used.

In the SMB, each column is installed with a multiport valve and an additional
multiport valve is installed to guide the liquid flow at the port of extract.

SEPARATION OF BDO AND PDO

SEPARATION OF BDO AND PDO

A check valve is also installed for each column to prevent the back flow of
liquid when switching the multiport valve to simulate the movement of a so

back pressure regulators, with 50 psi and 250 psi, are installed to stabilize
the flow rate and the pressure of the SMB system.

During packing of the eight PVC columns, an equal weight of resin is

individually prepared for each column and gradually loaded into the column
to assure packing homogeneity.

Various parameters are calculated like dead volume dead time, adsorption
isotherms,mass transfer coefficients by carrying out the displacement
chromatography with HPLC system.

SEPARATION OF PDO AND BDO

A stainless HPLC column 1.0 25 cm is used for the investigation of the

adsorption isotherm.

Here , during experiment we are keeping flow rate constant and changing the
time of switching valves.

After the steady state is reached, concentration of BDO and PDO were
calculated and it was observed that experiments conducted with switching
times ranging from 9 to 11 mins can be accounted for as experiments with
separable operating conditions

From the above experiment it was found that optimised separation is 100%
pure BDO and 92.56% pure PDO, the productivity of the SP70 is 0.101 KKD
(kg/kg/day), and the amount of water recycling is 300 L/kg.

REFERENCE