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Development of industrial scale Centrifugal Partition Chromatography

Article in Planta Medica · November 2015

DOI: 10.1055/s-0035-1565770

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Laszlo Lorantfy László Frici Németh

RotaChrom Technologiai Kft LiLiChro Ltd.
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 Development of Industrial Scale Centrifugal
Partition Chromatography
Centrifugal Partition Chromatography (CPC) is a special chromatographic technique where
both stationary and mobile phase are liquid, and the stationary phase is immobilized by a strong
László Lorántfy, László Németh centrifugal force (1. picture). Similar techniques are Counter-current Chromatography (CCC)
ROTACHROM Technológiai Kft. and Counter-current extraction (CCE), which has been used for natural product purification
Hungary - 2370 Dabas, Park u. 6. for decades.
www.rotachrom.com - e-mail: ll@rotachrom.com
The main advantage is the cost-effectiveness, since it does not need any expensive and bulky
solid stationary phase, and both quantity and quality requirements for solvents are less
decreased contrast to standard liquid chromatographic techniques. CPC consists of series
connected network of extraction cells, which operates as elemental extractors, and the
efficiency is guaranteed by the cascade [1]. CPC instruments vary on scale from 50 ml to 25
liter in column volume, and from 5 ml/min to 500 ml/min on flow rate, however all advantages
are realized on bigger scale use in industry. Up to date there were no available cGMP compliant
instruments, and no instruments that could be used for purification on industrial scale (flor
rates over 1 liter/min).
Our development started with the flow-simulation of the elementary extraction cells. The
current extraction cells available has big dead-volume and extensive back-mixing (2. picture).
Our studies showed that with the modification of the cell geometry and by using packing a
1. picture: schematic representation of CPC more efficient technique can be developed, outdating current research [2]. Our cell designs (2.
http://www.armen-instrument.com/downloads/Armen-Introduction-
CPC-CCC.pdf
picture) are currently patent pending.
First prototype (4,5. picture) was built in September, 2014, with modifications in January and
May. The prototype is still in operation with success, and production of final model will start
in August. We already achieved same performance (plate number, resolution) as CPC
competitors (Armen, Kromaton, Partitron) at fraction pressure and column length. A separation
with sample of fatty-acid derivatives was achieved at 10 bars instead of 50, with run times of
5 minutes instead of 100 (3. picture). All other performance parameters were kept the same.
Comparing our CPC to former techniques, we have numerous examples showing effective
separations, like for pinosylvins (see other poster), showing that CPC is applicable on a wide
range of materials, and with time it will substitute most preparative-LC processes.
Our instruments range from 300ml to 50 liter of column volume, from 200ml/min to 10 l/min
flow rate. This means that this new industrial machine can adopt to productions of few grams
up to tons / month. Our team (6. picture) is proud to continue the way of Hungarian
2. picture: flow inside Kromaton and RotaChrom CPC cells chromatographic inventors, like Csaba Horvath, inventor of HPLC.

3. picture: left: separation of fatty-acid derivatives on an Armen SCPC-250; right: separating the same on RotaChrom-CPC 4. picture: Prototype cell block

6. picture: The RotaChrom TEAM with HQ

References:
[1] Berthod A. Countercurrent Chromatography, 1st edition. Amsterdam: Elsevier; 2002
[2] Schwienheer C, Merz J, Schembecker G. Investigation, comparison and design of chambers
used in Centrifugal Partition Chromatography on basis of flow pattern and separation experiments
Evaulation of CPC separation efficiency for different types of chamber geometries on the basis of
5. picture: RotaChrom CPC prototype flow pattern and separation experiments. Journal of Chromatography A, in press

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