Virginia Tech
    • Log in
    View Item 
    •   VTechWorks Home
    • ETDs: Virginia Tech Electronic Theses and Dissertations
    • Doctoral Dissertations
    • View Item
    •   VTechWorks Home
    • ETDs: Virginia Tech Electronic Theses and Dissertations
    • Doctoral Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Synthesis and Structure-property Evaluation of Novel Cellulosic Polymers as Amorphous Solid Dispersion Matrices for Enhanced Oral Drug Delivery

    Thumbnail
    View/Open
    Liu_H_D_2014.pdf (5.784Mb)
    Downloads: 2330
    Supporting documents (922.2Kb)
    Downloads: 55
    Date
    2014-02-03
    Author
    Liu, Haoyu
    Metadata
    Show full item record
    Abstract
    The use of amorphous solid dispersions (ASDs) is an effective and increasingly widely adopted approach for solubility and bioavailability enhancement of hydrophobic drugs. Cellulose derivatives have strong potential as ASD polymers. We demonstrate herein design, synthesis and structure-property relationship characterization of a new series of organo-soluble cellulose omega-carboxyalkanoates for ASDs, by two different synthetic approaches. These carboxyl-containing cellulose mixed-esters possessed relatively high Tg values with sufficient differences versus ambient temperature, useful to prevent drug mobility and crystallization during storage or transport. Screening experiments were utilized to study the impact of ASD polymers including our new family of cellulose Ω-carboxyesters on both nucleation induction time and crystal growth rate of three poorly soluble model drugs from supersaturated solutions. Attributed to relatively rigid structures and bulky substituent groups, cellulose derivatives were more significant crystallization inhibitors compared to the synthetic polymers. The effective cellulose omega-carboxyesters were identified as possessing a similar hydrophobicity to the drug molecule and high number of ionization groups. Among them, cellulose acetate suberate prepared by us was an extraordinary solution crystal growth inhibitor for ritonavir and its formulated solid dispersions provided a substantial 15-fold enhancement of apparent solution concentration vs. the equilibrium solubility of the crystalline drug. To offset the issue of slow drug release from some cellulose omega-carboxyester based formulations, a new class of amphiphilic cellulosic polymers with hydrophilic oligo(ethylene oxide)-containing side chains was developed via versatile synthetic pathways, and the evaluation of these materials alone or by pairwise polymer blends will be performed as ASD matrices for the enhancement of drug solubility and stability.
    URI
    http://hdl.handle.net/10919/54934
    Collections
    • Doctoral Dissertations [15770]

    If you believe that any material in VTechWorks should be removed, please see our policy and procedure for Requesting that Material be Amended or Removed. All takedown requests will be promptly acknowledged and investigated.

    Virginia Tech | University Libraries | Contact Us
     

     

    VTechWorks

    AboutPoliciesHelp

    Browse

    All of VTechWorksCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    Log inRegister

    Statistics

    View Usage Statistics

    If you believe that any material in VTechWorks should be removed, please see our policy and procedure for Requesting that Material be Amended or Removed. All takedown requests will be promptly acknowledged and investigated.

    Virginia Tech | University Libraries | Contact Us