KUKU

KU ScholarWorks

  • myKU
  • Email
  • Enroll & Pay
  • KU Directory
    • Login
    View Item 
    •   KU ScholarWorks
    • Dissertations and Theses
    • Theses
    • View Item
    •   KU ScholarWorks
    • Dissertations and Theses
    • Theses
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Quantification of Trace Levels of Active Oxygen in Pharmaceutical Excipients

    Thumbnail
    View/Open
    Staub_ku_0099M_15675_DATA_1.pdf (3.082Mb)
    Issue Date
    2017-12-31
    Author
    Staub, Stephanie Anne
    Publisher
    University of Kansas
    Format
    103 pages
    Type
    Thesis
    Degree Level
    M.S.
    Discipline
    Pharmaceutical Chemistry
    Rights
    Copyright held by the author.
    Metadata
    Show full item record
    Abstract
    Pharmaceutical drug products contain various excipients in combination with the active pharmaceutical ingredient (API), and those excipients have the potential to have as impurities reactive oxygen species that can react directly with the API and lead to oxidative degradation. Such degradation can impact long-term stability of the drug product, reduce drug product purity, limit shelf life, and increase time to market. Peroxy compounds are a common class of such reactive impurities, but there is an absence in the literature of a method for detection of total peroxide level in pharmaceutical excipients when the identity of the peroxy contaminant is not known. In this thesis, novel modifications were made to the 1966 ASTM E 299-08 method for enhanced and robust detection of active oxygen in pharmaceutical excipients. The modified ASTM E 299-08 method was evaluated using spiked solutions of hydrogen peroxide, a hydroperoxide compound, and a peroxide compound. Liquid and solid excipients were then evaluated for active oxygen levels to demonstrate the utility and breadth of the modified method to cover a wide range of excipients. The polyethylene glycol (PEG) class of compounds was chosen for more in-depth evaluation due to their susceptibility to autoxidation and the existence of various molecular weight grades of PEG compounds. PEG 1000 was chosen along with lestaurtinib (CEP-701) to prepare a novel drug product, which was evaluated on stability for active oxygen and assay impurity levels. The results showed that the modified ASTM E 299-08 method successfully quantified both the total active oxygen levels and the CEP-701 peroxy impurity levels, which agreed with those obtained by an HPLC assay method. The modified ASTM E 299-08 method has important applicability in the pharmaceutical industry as a method that can be used for preliminary screening of excipients and new formulations to predict potential oxidative degradation reactions.
    URI
    http://hdl.handle.net/1808/26161
    Collections
    • Pharmaceutical Chemistry Dissertations and Theses [141]
    • Theses [3906]

    Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.


    We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.


    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    Browse

    All of KU ScholarWorksCommunities & CollectionsThis Collection

    My Account

    Login

    Statistics

    View Usage Statistics

    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    The University of Kansas
      Contact KU ScholarWorks
    Lawrence, KS | Maps
     
    • Academics
    • Admission
    • Alumni
    • Athletics
    • Campuses
    • Giving
    • Jobs

    The University of Kansas prohibits discrimination on the basis of race, color, ethnicity, religion, sex, national origin, age, ancestry, disability, status as a veteran, sexual orientation, marital status, parental status, gender identity, gender expression and genetic information in the University’s programs and activities. The following person has been designated to handle inquiries regarding the non-discrimination policies: Director of the Office of Institutional Opportunity and Access, IOA@ku.edu, 1246 W. Campus Road, Room 153A, Lawrence, KS, 66045, (785)864-6414, 711 TTY.

     Contact KU
    Lawrence, KS | Maps