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Thesis: Use of supercritical extraction in production of drug and health-promoting components



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

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