Adsorptive Radial
Column Filtration (ARCF)
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Improved throughput and product recovery in large scale productions on
activated Aluminum Oxide and Silica.
In the production of non-proteinous natural
drugs or food additives from natural sources, solvent extraction is a common first step.
The subsequent fractionation or concentration mostly involves an adsorption step to purify
or decolorize the product. In some occasions this adsorption step was found to be
old-fashioned, unhealthy, slow and labour intensive.
To improve upon all of these aspects of this selective filtration step,
without compromising the quality of the product, Adsorptive Radial Flow Filtration was
developed in a joint venture by ICN Biomedicals GmbH and Sepragen Europe.
Repeated ‘real-live’ results have proven the applicability and
economical benefit of this industrial Adsorptive Radial Column Filtration process.
At the purification, after
solvent extraction, of a natural (registered) drug, the net throughput using ARCF
increased 100x as compared with the conventional process, while the capacity
increased 3x per adsorptive matrix-volume. The purity and yield of the drug was
found to be comparable or better (data not published).
Several valuable food products, aroma’s
and a number of natural drugs are extracted from the original (plant) materials or
obtained through cell culture (fermentations).
Starting from these natural sources, a common first step in the
purification of a product, is a solvent extraction followed by a selective filtration to
decolorize or remove >80% of the bulk contaminants and to reduce the process volume.
Selective filtration is done by feeding the
dirty solvent extract through a short (low) bed of an adsorptive matrix often in large
(open-air) Buchner-type funnels or ‘low-technology’ column systems which are run
under vacuum, hydrostatic or gas pressure.
Two typical modes are found: ‘Frontal Elution’ or ‘Solid
Phase Extraction’.
‘Frontal Elution’ of the extract is commonly used when the
extract is complex and/or colored. The extract is fed through a bed of low-cost
high-capacity EcoChrom™ Aluminum oxide or EcoChrom™ Silica while the decolorized
product is collected. After saturation of the adsorptive matrix, this matrix is
discarded and the method can be repeated (ICN Biomedicals is setting up schemes to take
back the spent Alumina).
‘Solid Phase Extraction’ of the mixture is preferred when the
product is highly diluted. The product is selectively bound to the EcoChrom™
adsorptive matrix and eluted in a small volume after saturation of the matrix. The
adsorptive matrix is discarded after the elution of the product.
Short bed heights are used to increase throughput and reduce back-pressure
therefore reducing cost. The selectivity of the filtration process is determined by the
right combination between the adsorptive matrix and solvent.
At scale-up of the process, the bed volume of the adsorption step has to
be scaled-up too. Taller columns or an increase in funnel diameter have disadvantages.
Taller columns will result in:
exponential, undesired, increase in backpressure
high likelyhood of blockages due to accumulation of dirt at the column
inlet.
Wide diameter ‘pancake’ beds (buchner funnels):
product distribution problems
result in major handling issues
when open to air, result in health issues.
In both cases this results in a sub-optimal use of the matrix and reduced
throughput. Alternatively it requires investments in equipment or more expensive matrices.
Furthermore, because the extraction solvents are intrinsically dangerous,
high operating pressures are not desirable in this stage of the process.
Radial Flow Technology Background:
In the early ‘80’s Radial
Flow Column (RFC) technology was developed to offer chromatography columns for industrial
scale processes with adsorptive resins. During the last decade RFC has proven to be the tool of choice for
fast and economical adsorptive separations. Superflo® process columns have low bed
heights of 10cm or 15 cm and are available up to column volumes of 500 Liter. Nevertheless
the Superflo® columns require only limited floor space, approx. 1m2 at a
column volume of 500 Liter. Typical running pressures of the Superflo® columns are
in the range of 0,1 to 0,5 bar at a flowrate of 0,5 to 1 (CV/min) Column Volume per
minute.
Superflo® columns were initially designed for compressable
adsorptive resins. In this application, the Adsorptive Radial Column Filtration
application, irregular silica and irregular aluminum oxide are added to this list.
Packing and unpacking of the Radial Flow, Superflo® columns is automized, reproducible
and fast. Superflo® column can be packed dry or in slurry packing mode with ICN
EcoChrom™ Aluminum-Oxide or Silica.
Packing of any column size takes only minutes + the time to prepare a
10-50% slurry.
The unique hydro-dynamic properties and geometry of the Superflo®
columns, combine the advantages of a short bed with optimal feed distribution, high
flowrates and an extremely large (20 to 40 fold) inlet surface area in a compact column.
The distribution of the dirty feed on the adsorptive matrix over the giant inlet
surface area is very even and ‘natural’, resulting in excellent peak-shape and
optimal use of the adsorbent bed. At the same time it prevents clogging of the
matrix as there is never a local overload situation at product loading.
The combination of these characteristics of Sepragen Superflo® columns
offer the unsurpassed economical industrial benefits and the reason why (Radial Flow)
Chromatography can be applied for even low-added-value molecules in the food and beverage
industry.
Superflo® Column Design:
The Superflo® column can be seen as a
column body with 3 concentrical cylinders in it (figure A). From outside to inside: the
column body (3), the Inlet frit (4), the Outlet frit (5) and the Collector rod (6). The
space between the Inlet and the Outlet frit is filled with the adsorptive resin. The
flow through the column (see fat arrows) will enter the column at the inlet (1) pass
through the radially arranged channnels (2) to the outer rim of the column body. Then the
solvent will distribute in the capillary space between column body and Inlet frit, through
the Inlet frit, through the resin, through the Outlet frit, into the central cylinder
bordered by the collector rod and is collected at the column outlet (7). At scale-up
an increase volume is an increase in height of the column. Therefore this will have no
effect on the bed height of the column, and optimal performance will be unaffected.
In the upper and lower distribution plates, we find the packing and unpacking ports.
Figure A: Cut-out view of a Superflo® , Radial Flow Column
Table 1: Superflo® columns, standard sizes
| Size (volume) |
Bed Height |
Application |
| 50 - 1.500 ml |
3.5 cm |
Laboratory scale, feasibility study |
| 5 or 10 Liter |
5 cm |
Pilot scale, small scale productions |
| 10 to 300 Liter |
10 cm |
Process scale, Large scale productions |
| 25 to 500 Liter |
15 cm |
Process scale, Large scale productions |
Advantages of the Adsorptive Radial Column Filtration
process:
The Adsorptive Radial Column Filtration process was
developed to address a number of the common occuring problems at the selective filtration
step in the purification process.
Operator Health:
Toxic solvents (DCM, Ethyl-acetate, MEK, Alcohols etc.), demand containment.
Automation:
Automation will increase reproducibility and reliability of the process.
Throughput:
Higher throughput will reduce production cost and time to market.
The Adsorptive Radial Column
Filtration process can be used at industrial scales and combines excellent performance
and high throughput at the selective filtration of products from solvent extracts of
natural sources. Automated column packing with EcoChrom™ Aluminum-Oxide (e.g.
63-200) takes only a few minutes and can be done dry or using a peristaltic pump (with
slurry). The net dynamic-bonding capacity of the adsorbents has shown to be
increased by a factor 3 which proves optimal use of the adsorbents. Operating
pressures at flow rates up to 5CV/min with the 63-200m m resin lie below 1Bar. Total
processing time has been reported up to 30 times faster compared to the conventional
process resulting in a throughput increase of approx. 100x in comparison with the
conventional processes.
All goals for for the development of
the Adsorptive Radial Column Filtration process have been met or exceeded. The
applicability of the technology has been proven in all subsequent trials which have been
conducted since its development.
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