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    • University of Missouri-Columbia
    • Graduate School - MU Theses and Dissertations (MU)
    • Theses and Dissertations (MU)
    • Dissertations (MU)
    • 2019 Dissertations (MU)
    • 2019 MU dissertations - Access restricted to UM
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    Formulation development of a novel antivirulence compound for enhanced pharmocokinetic properties

    Wang, Nan
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    [PDF] WangNan.pdf (10.97Mb)
    Date
    2019
    Format
    Thesis
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    Abstract
    [ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] A novel antivirulence compound CCG-211790 (termed as C790 in this context), has demonstrated significant inhibition against several severe antibiotic-resistant bacteria. However, its clinical use is restricted by formulation challenges arising from its poor aqueous solubility. In this dissertation, plate-like or tube-like C790 nanoparticles with thickness down to one hundred nanometers have been successfully produced using antisolvent precipitation- ultrasonication method. C790 nanoparticles, in the form of suspensions, have exhibited remarkably enhanced dissolution rate which obtained almost 100% release within 5 minutes under in-vitro sink environment. The concentration of surfactants in antisolvent and the ultrasonic cavitation intensity are regarded as two of the most important parameters affecting particle size and morphology. Small plate-like particles were produced with low surfactant concentration (below or close to their critical micelle concentration) and high cavitation intensity, while large curved plate-like or tube-like particles were produced with high surfactant concentration (far above their CMC) and low cavitation intensity. The cavitation intensity can be controlled by the volume of water filled in ultrasonic tank, and there is a threshold below which the particle size can be maintained in a narrow range, e.g. of 320-360 nm when 0.02% w/v Tween 80 is applied. Both the small platelike particles and the large curved-plate/tube-like particles carry high magnitude of zeta potential that provides good electrostatic stabilization for at least 6 or 12 weeks depending on particle size and morphology when storing at 4 [degrees]C and room temperature. Both the small plate-like particles and the large curved-plate/tube-like particles, in the form of suspension, have significant advantages over solution formulations (PEG/PG and PEG/Tween formulations) for intravenous administration. In addition, these two suspensions, which have different particle size and morphology, have increased oral bioavailability from 8.0% of the bulk powder formulation to 28.6% and 22.7%, respectively. The C790 nanosuspensions, in particular the one with small plate-like particles, has demonstrated promising clinical potential as oral and intravenous formulations.
    URI
    https://hdl.handle.net/10355/76182
    https://doi.org/10.32469/10355/76182
    Degree
    Ph. D.
    Thesis Department
    Mechanical and aerospace engineering (MU)
    Rights
    Access is limited to the campuses of the University of Missouri
    Collections
    • 2019 MU dissertations - Access restricted to UM
    • Mechanical and Aerospace Engineering electronic theses and dissertations (MU)

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