(431f) Novel Concepts for Continuous Purification of APIs Using Electro- Chromatography

In pharmaceutical industry batch processing still dominates the manufacturing of the active
pharmaceutical ingredients (APIs). One example is liquid chromatography, which is one of
the basic separation methods for biosynthetic products but is still operated in batch mode. As
continuous processes offer many advantages, approaches to develop continuous
chromatographic processes have become increasingly important.
An effort in this area is the CAEC project, which deals with the development of a continuous
annular electro-chromatography (CAEC) prototype [1]. This prototype combines the
advantages of electrophoresis and preparative liquid chromatography in a continuous
operation mode, thus leading to both, a high throughput and a high separation efficiency.
Furthermore, the eluting analytes are monitored with an online detection system to ensure a
continuous quality control.
We present the design, characterization and implementation of the stationary phase in this
novel prototype. The stationary phase is based on a silica monolith which can be adjusted to
the separation problem with functional groups, such as amino groups for ion exchange
chromatography or alkyl chains for reversed phase chromatography [2]. In this way, not
only the liquid phase but also the stationary phase can be adapted to specific problems
which makes the CAEC universally applicable. The monolith is supported with silica particles
that prevent the stationary phase from shrinking. This combination of particles and the
monolithic structure increases the mechanical and chemical stability of the stationary phase
while preserving a high porosity to achieve a high throughput.
The macroporous one-piece material was implemented in several moulds, such as a planar
test cell that represents a fraction of the annular prototype and already allows a continuous
separation via electro-chromatography. In this planar test cell hydrodynamics and heat
transfer [3] were investigated and standard test systems could be successfully separated
achieving theoretical plate numbers of over 20000 per meter and a throughput of up to
50 ml/h.
In addition, we present a simulation program that is implemented in MATLAB to support the
design of the chromatographic experiments. The program is based on a stochastic (Monte
Carlo) approach and algorithms for convection, diffusion and retention are implemented [4].
With this program chromatograms can be simulated based on the population distribution of
the analytes. Therefore, these simulations can help to determine the suitable stationary as
well as mobile phase for a given separation problem. Moreover, the molecular interactions of
the analytes with the stationary phase were studied using molecular dynamics (MD)
simulations.
Overall, the outcomes of our approaches are powerful tools for future separation tasks in
pharmaceutical industry and can be individually assigned to a broad spectrum of problems.
This work is supported by the 7th Research Framework Programme of the European
Commission (Grant agreement number: NMP2-SL-2008-206707)
[1] https://caec.bci.tu-dortmund.de/
[2] Gruber-Woelfler, H.; Braunbruck, M.-G.; Feenstra, P.W.; Laskowski, R.; Bart, Khinast, J.G., Oral
Presentation, 9th International Congress of Chemical and Process Engineering CHISA 2010,
Prague, August, 2010
[3] Laskowski, R.; Bart, H.-J.; Gruber-Wölfler, H.; Feenstra, P.; Braunbruck, M.-G.; Khinast, J.;
Hofmann, C.; Menges, G.; Werner, B.; Löb, P.; Hessel, V.:, 17th International Symposium on
Electro- and Liquid Phase-separation Techniques (ITP), 2010, Baltimore, USA.
[4] McGuffin, V.L.;Wu, P.R.; Journal of Chromatography A, 722 (1996) 3