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Thesis: Use of supercritical extraction in production of drug and health-promoting components
04.02.2008
VTT’s Senior Research Scientist Martti Alkio presents his thesis “Purification of pharmaceuticals and nutraceutical compounds by sub- and supercritical chromatography and extraction” at the University of Helsinki (Fabianinkatu 33) on 8th February 2008.
Martti Alkio used super- and subcritical extraction to separate oils from the
herbal plant Angelica archangelica. The effect of extraction parameters was
studied and sensory analyses of the extracts were done by an expert panel. The
results of the sensory analyses were compared to the analytically determined
contents of the extracts.
Sub- and supercritical fluid
chromatography (SFC) was used to separate and purify high-value
pharmaceuticals. Chiral SFC was used to separate the enantiomers of racemic
mixtures of pharmaceutical compounds. Very low (cryogenic) temperatures were
applied to substantially enhance the separation efficiency of chiral SFC. The
thermodynamic aspects affecting the resolving ability of chiral stationary
phases are briefly reviewed.
The process production rate
which is a key factor in industrial chromatography was optimized by empirical
multivariate methods. General linear model was used to optimize the separation
of omega-3 fatty acid ethyl esters from esterized fish oil by using
reversed-phase SFC. Chiral separation of racemic mixtures of guaifenesin and
ferulic acid dimer ethyl ester was optimized by using response surface method
with three variables per time. Alkio proved that by optimizing four variables
(temperature, load, flowate and modifier content) the production rate of the
chiral resolution of racemic guaifenesin by cryogenic SFC could be increased
several fold compared to published results of similar application.
Also
a novel pressure-compensated design of industrial high pressure
chromatographic column was introduced, using the technology developed in
building the deep-sea submersibles Mir 1 and 2. A demonstration SFC plant was
built and the immunosuppressant drug cyclosporine A was purified to meet the
requirements of US Pharmacopoeia.
Further information:
VTT,
Martti Alkio, MSc, Senior Research
Scientist, tel. +358 20 722 5300
Publication
in the Internet