Date of Award


Degree Type


Degree Name

Doctor of Philosophy


Cyclosporine, or Cyclosporin A is an important new immunosuppressant drug, now used to prevent the immune rejection of a variety of organ transplants. Cyclosporine is produced by the fungus Beauvaria nivea ATCC 34921, also called Tolypocladium inflatum NRRL 8004. The current commercial Cyclosporine extraction process uses liquid organic solvents, with the risk of possibly hazardous residues in the final product. Governments are now aggressively regulating exposure to organic solvents. In view of this, a supercritical CO{dollar}\sb2{dollar} extraction process, which results in no organic solvent residues, is very good alternative.;Cyclosporine solubility in supercritical CO{dollar}\sb2{dollar} was studied using a newly designed apparatus to determine the feasibility of the extraction process. Cyclosporine solubilities up to 16-20 mg/mL of supercritical CO{dollar}\sb2{dollar} could be attained easily. The pressures and temperatures used ranged from 8.2 MPa to 34.0 MPa and 308.5 K to 343 K respectively. Cyclosporine mole fraction was found to correlate linearly with reduced densities above 1.5. When a methanol co-solvent was added Cyclosporine solubility in supercritical CO{dollar}\sb2{dollar} increased up to 20 times.;Cyclosporine extractions from the mycelia of the fungus Beauvaria nivea were done with supercritical CO{dollar}\sb2{dollar} at 32.0 MPa and 314 K. The highest extraction yields, with 70 to 80% of the original Cyclosporine present in the mycelia removed, were achieved using mycelia containing 7.2 to 29.5% moisture. Completely dried mycelia had lower extraction yields. The addition of methanol showed no effect on the Cyclosporine extraction yields. Co-extracted materials observed during the extraction experiments were tentatively identified as lipids. Scanning electron micrographs were taken of the mycelial structure and used to visualize the physical barriers to Cyclosporine removal.;The supercritical CO{dollar}\sb2{dollar} extraction process was found to be feasible for Cyclosporine removal from mycelia. This work contains the first report of its kind in the literature on the supercritical CO{dollar}\sb2{dollar} extraction of Cyclosporine from the mycelia of Beauvaria nivea, and the first data showing Cyclosporine solubility in supercritical CO{dollar}\sb2{dollar}. Further work remains to be done to optimize the yields and rates of supercritical CO{dollar}\sb2{dollar} extraction of Cyclosporine from mycelia.



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