TexasScholarWorks
    • Login
    • Submit
    View Item 
    •   Repository Home
    • UT Electronic Theses and Dissertations
    • UT Electronic Theses and Dissertations
    • View Item
    • Repository Home
    • UT Electronic Theses and Dissertations
    • UT Electronic Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Pharmaceutical technologies for improving drug loading in the formulation of solid dispersions

    Thumbnail
    View/Open
    ODONNELL-DISSERTATION-2011.pdf (5.366Mb)
    Date
    2011-12
    Author
    O'Donnell, Kevin Patrick
    Share
     Facebook
     Twitter
     LinkedIn
    Metadata
    Show full item record
    Abstract
    It is estimated that 90% of new chemical entities in development pipelines exhibit poor aqueous solubility. For compounds not limited by biological membrane permeability, this poor aqueous solubility is the limiting factor in bioavailability. Therefore, the formulation of such drugs has primarily been centered on improving dissolution properties. Traditional approaches for overcoming poor aqueous solubility include salt formation of the active ingredient, complexation, the use of surface active agents, formulation into oil based systems, particle size reduction, or a combination of these methods. More recently amorphous solid dispersions have been explored. Currently, the drug loading within solid dispersions is limited resulting in large quantities of the formulation being required for a therapeutically relevant dose. In the frame of the work herein, Thin Film Freezing was utilized to generate high drug loaded amorphous solid dispersions of the poorly water soluble drug phenytoin utilizing a hydrophilic polymer or an amphiphilic graft copolymer for system stabilization. Additionally a new solvent removal technique, atmospheric freeze drying, was investigated for removal of the solvents used during Thin Film Freezing. The Thin Film Freezing materials were subsequently incorporated into a polymeric carrier for solid dispersion formulation by a novel fusion production technique termed Kinetisol® dispersing. Studies of the solid dispersions produced by Thin Film Freezing revealed an amorphous system had been obtained for both stabilizing polymers. The formulation containing a hydrophilic carrier was capable of achieving supersaturation. Conversely, the amphiphilic graft copolymer demonstrated a phenytoin-polymer interaction resulting in poor dissolution. Atmospheric freeze drying of the Thin Film Freezing product demonstrated that the alternative drying technique generated powders with significantly improved handling properties as a result of reduced electrostatic interactions due to the increased pore size, reduced surface area, larger particle size, and higher, though acceptable, residual solvent levels. The use of Thin Film Freezing powders during Kinetisol Dispersing resulted in a single phase amorphous system while solid dispersions produced from physical mixtures of bulk materials were amorphous two-phase systems. This indicates that the use of amorphous drug compositions during solid dispersion production may increase drug loading in the final system while remaining single phase in nature.
    Department
    Pharmacy
    Description
    text
    Subject
    Solid dispersion
    Fusion production
    Kinetisol dispersing
    Atmospheric freeze drying
    Thin film freezing
    High drug loading
    Supersaturation
    Polymeric carrier
    URI
    http://hdl.handle.net/2152/ETD-UT-2011-12-4493
    http://hdl.handle.net/2152/20661
    Collections
    • UT Electronic Theses and Dissertations

    University of Texas at Austin Libraries
    • facebook
    • twitter
    • instagram
    • youtube
    • CONTACT US
    • MAPS & DIRECTIONS
    • JOB OPPORTUNITIES
    • UT Austin Home
    • Emergency Information
    • Site Policies
    • Web Accessibility Policy
    • Web Privacy Policy
    • Adobe Reader
    Subscribe to our NewsletterGive to the Libraries

    © The University of Texas at Austin

     

     

    Browse

    Entire RepositoryCommunities & CollectionsDate IssuedAuthorsTitlesSubjectsDepartmentsThis CollectionDate IssuedAuthorsTitlesSubjectsDepartments

    My Account

    Login

    Statistics

    View Usage Statistics

    Information

    About Contact Policies Getting Started Glossary Help FAQs

    University of Texas at Austin Libraries
    • facebook
    • twitter
    • instagram
    • youtube
    • CONTACT US
    • MAPS & DIRECTIONS
    • JOB OPPORTUNITIES
    • UT Austin Home
    • Emergency Information
    • Site Policies
    • Web Accessibility Policy
    • Web Privacy Policy
    • Adobe Reader
    Subscribe to our NewsletterGive to the Libraries

    © The University of Texas at Austin