Purification of pharmaceuticals and nutraceutical compounds by sub- and supercritical chromatography and extraction

Dissertation

Martti Alkio

Research output: ThesisDissertationCollection of Articles

Abstract

This thesis discusses the use of sub- and supercritical fluids as the medium in extraction and chromatography. Super- and subcritical extraction was used to separate essential oils from 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 diethyl ester was optimized by using response surface method with three variables per time. It was found 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 severalfold compared to published results of similar application. A novel pressure-compensated design of industrial high pressure chromatographic column was introduced. A demonstration SFC plant was built and the immunosuppressant drug cyclosporine A was purified to meet the requirements of US Pharmacopoeia. A smaller semi-pilot size column with similar design was used for cryogenic chiral separation of aromatase inhibitor Finrozole for use in its development phase 2.
Original languageEnglish
QualificationDoctor Degree
Awarding Institution
  • University of Helsinki
Supervisors/Advisors
  • Koskimies, Salme, Supervisor, External person
  • Yli-Kauhaluoma, Jari, Supervisor, External person
Award date8 Feb 2008
Place of PublicationEspoo
Publisher
Print ISBNs978-951-38-7077-5
Electronic ISBNs978-951-38-7078-2
Publication statusPublished - 2008
MoE publication typeG5 Doctoral dissertation (article)

Fingerprint

Chromatography
Purification
Guaifenesin
Pharmaceutical Preparations
Cryogenics
ferulic acid
Esters
Aromatase Inhibitors
Parameter extraction
Supercritical fluids
Enantiomers
Fish Oils
Omega-3 Fatty Acids
Volatile Oils
Immunosuppressive Agents
Dimers
Cyclosporine
Supercritical Fluid Chromatography
Demonstrations
Thermodynamics

Keywords

  • pharmaceuticals
  • nutraceuticals
  • purification
  • supercritical fluid extraction
  • subcritical chromatography
  • supercritical chromatography
  • CO2 extraction

Cite this

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title = "Purification of pharmaceuticals and nutraceutical compounds by sub- and supercritical chromatography and extraction: Dissertation",
abstract = "This thesis discusses the use of sub- and supercritical fluids as the medium in extraction and chromatography. Super- and subcritical extraction was used to separate essential oils from 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 diethyl ester was optimized by using response surface method with three variables per time. It was found 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 severalfold compared to published results of similar application. A novel pressure-compensated design of industrial high pressure chromatographic column was introduced. A demonstration SFC plant was built and the immunosuppressant drug cyclosporine A was purified to meet the requirements of US Pharmacopoeia. A smaller semi-pilot size column with similar design was used for cryogenic chiral separation of aromatase inhibitor Finrozole for use in its development phase 2.",
keywords = "pharmaceuticals, nutraceuticals, purification, supercritical fluid extraction, subcritical chromatography, supercritical chromatography, CO2 extraction",
author = "Martti Alkio",
year = "2008",
language = "English",
isbn = "978-951-38-7077-5",
series = "VTT Publications",
publisher = "VTT Technical Research Centre of Finland",
number = "673",
address = "Finland",
school = "University of Helsinki",

}

Purification of pharmaceuticals and nutraceutical compounds by sub- and supercritical chromatography and extraction : Dissertation. / Alkio, Martti.

Espoo : VTT Technical Research Centre of Finland, 2008. 130 p.

Research output: ThesisDissertationCollection of Articles

TY - THES

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AB - This thesis discusses the use of sub- and supercritical fluids as the medium in extraction and chromatography. Super- and subcritical extraction was used to separate essential oils from 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 diethyl ester was optimized by using response surface method with three variables per time. It was found 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 severalfold compared to published results of similar application. A novel pressure-compensated design of industrial high pressure chromatographic column was introduced. A demonstration SFC plant was built and the immunosuppressant drug cyclosporine A was purified to meet the requirements of US Pharmacopoeia. A smaller semi-pilot size column with similar design was used for cryogenic chiral separation of aromatase inhibitor Finrozole for use in its development phase 2.

KW - pharmaceuticals

KW - nutraceuticals

KW - purification

KW - supercritical fluid extraction

KW - subcritical chromatography

KW - supercritical chromatography

KW - CO2 extraction

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SN - 978-951-38-7077-5

T3 - VTT Publications

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