Chromatography: Preparative Supercritical Fluid Chromatography (SFC)

Preparative SFC is more and more used in research and development laboratories and pilot plants of the pharmaceutical and fine chemical industries. SFC is particulary interesting for the purification of :

• chiral compounds
• actives or intermediates from complex mixtures
• lipophilic compounds

Novasep Supersep™ units are installed in multiple pharmaceutical and fine chemical companies to support:

• medicinal chemistry
• supply of pre-clinical and APIs clinical tests
• commercial production

Principle of operation

Due to the low viscosity and high diffusivity of the supercritical CO2, preparative SFC ensure faster purification than traditional preparative HPLC. The principle is descibed below.

Cold liquid CO2 is pumped (1 2). Prior to entering the column, it is heated and becomes supercritical (2 3). Because of its low viscosity, the pressure at the column outlet is almost identical to the pressure at the column inlet (3 4). At the column outlet, the mobile phase is decompressed and heated and becomes gaseous (4 5). Products are recovered in cyclones of appropriate design. The gaseous CO2 is then cleaned and cooled down and returned to the tank.

Supersep™: Novasep preparative SFC systems

The Supersep™ line is the result of Novasep engineers' knowledge of Supercritical Fluid Extraction and High Performance Preparative Liquid Chromatography, combined with innovative technical solutions to handle supercritical fluids, recover efficiently purified materials and provide a fully automated and safe technology.
 
Supersep™ units are designed to address a large variety of purification problems, from laboratory scale to industrial production.
All Supersep™ units include CO2 recycling, which provide huge operating costs savings.

The product line:
Supersep™ units

MODEL	PRODUCTIVITY RANGE	PHOTO
Supersep™ 20-30	5 - 50 grams / day	view
Supersep™ 30-50	20 - 200 grams / day	view
Supersep™ 50	0.1 - 1 kg / day	view
Supersep™ 100	0.4 - 4 kg / day	N/A
Supersep™ 150	1 - 10 kg / day	view
Larger units available. Contact us

Optimum Design: performance, reliability and robustness.

The Supersep™ units are designed to work at elevated pressure (250 bar - 3,600 psi) and temperature (60 °C). Important process control and safety elements are installed on the units such as heat exchangers, pressure regulators, rupture discs, check-valves, etc. In addition, the control software monitors proper and safe operation at many locations in the flow path.
Polarity of the eluent can be modified by mixing co-solvent with CO2, in any proportions. Isocratic elutions, as well as pressure or co-solvent gradients can be programmed in operating recipes.
 
For optimum performance, specially adapted Prochrom® DAC columns are used to provide efficient, stable and scalable processes. The columns, rated at up to 300 bar (4,350 psi) are designed to prevent damage to the packing material at the high SFC operating pressures. Even fragile media such as some chiral stationary phases made with wide pore silicas can be utilised.

Prochrom LC50 SFC column	Supersep™20-30 unit

Product recovery & Eluent recycling

• An important consideration in the design of a PS-SFC unit is product recovery. After separation, decompression and heating, the product is a fog of micro-droplets or micro-crystals in gaseous carbon dioxide.
  The Supersep™ units are equipped with very efficient patented cyclone separators that allow over 99% of the purified material to be recovered.
   
• CO2 recycling is also provided as an integral part of the Supersep™ units. The recycled carbon dioxide (or a mixture with co-solvent) is cleaned prior to being recycled. Thanks to patented technology, eluent recycling is effective when a modifier is present.

Automation & Control

The control software, CHROMSOFT, compliant with GAMP4 (Good Automation Manufacturing Practice) and CFR 21 Part 11 guidelines. CHROMSOFT can be customized on request. The various actions and levels of interaction with CHROMSOFT are protected by passwords. The basic functions controlled by CHROMSOFT include operation of the pressure and eluent composition gradients, regulation of the pump(s) flow rate(s), monitoring of safety levels, batch management, acquisition of operating parameters (analogue and digital), communication with a DCS, etc. CHROMSOFT can also control ancillary equipment related to the chromatographic units (such as multiple tank levels, etc.).

CHROMSOFT offers two modes of operation : Maintenance (or Manual) and Automatic.
In Automatic mode, operation of the unit is based on a Purification Recipe which contains information related to the injected quantity, run time, unit configuration, solvent composition and fraction collection.

Automatic Fraction collection
If a chromatogram were absolutely stable run after run, fraction collection could be simply based on time. It is known, however, that there are often changes from run to run and that a simple collection sequence based on time is not sufficient. Embedded in CHROMSOFT, a sophisticated algorithm analyses the chromatogram in real time and automatically recalculates collection points in case of drifting chromatographic profiles (intelligent fraction collection). A specific graphical interface allows the operator to easily select optimum fraction collection parameters.

The potential of SF-Continuous Chromatography (SF-CC)

SF-CC has a bright future due to the possibility to control the eluent strength by proper pressure adjustment.
By properly setting the average pressure in the different zones of the SF-CC unit, a spatial gradient of eluent strength is produced (decreasing from Zone I to Zone IV). As a result, similar eluent flows can be used in Zones I and IV and the need for make-up flow is reduced. The consumption of eluent is thus decreased and the production rate is increased. This concept has been patented by Novasep Process.