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Adsorptive Radial Column Filtration (ARCF)

Overview

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).

Introduction

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

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.

Summary

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.

Conclusion

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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