Novel Polymeric Controlled Release Systems

  • Simon J. Holland

    Student thesis: Doctoral ThesisDoctor of Philosophy


    The primary object of this research has been to evaluate the
    potential of biodegradable polymers as matrices for macramolecular
    controlled drug release systems. Initial work was carried out on
    the in vitro breakdown of members of a novel poly ester copolymer
    series - polyhydroxybutyrate-co-hydroxyvalerate, in various
    aqueous buffers by bulk and surface measurements of the varying
    physical forms of the copolymer matrices.

    In line with the reported hydrolytic degradation of other
    polyesters the degradation was found to be by a predominantly
    homogeneous (bulk) mechanism. The initial molecular weight,
    copolymer composition and physical form of the polymer matrix
    determining the rate of hydrolysis. Comparison with established
    biodegradable suture materials showed a relatively slow rate of
    hydrolysis for the butyrate / valerate copolymers. However,
    differences in matrix molecular weights and crystallinities did
    make equivalent comparisons difficult. A link between matrix
    surface physical properties and the extent of bulk degradation was
    found, with the surface techniques providing a more detailed
    reflection of the extent of bulk matrix hydrolysis than weight
    loss measurements during the initial degradation stages.

    Drug release in the form of a series of macromolecular FITC
    dextran dyes was followed from two types of polyhydroxybutyrateco-
    hydroxyvalerate matrices (i.e. solvent cast films and cold
    compressed tablets). Release was found to occur predominantly by
    diffusion with matrix degradation playing an insignificant part in
    dye dissolution. Contrary to expectation, the rate of dye release
    increased with increasing dye molecular weight. This was due to
    changes in matrix porosity rather than dye diffusivity. Tablet dye
    release was found to be effected by the addition of various
    excipients, with matrix porosity governing the overall! release
    rate. It is suggested that the tabletted form could be used as
    sustained release non-disintegrating oral dosage forms.
    Date of Award1986
    Original languageEnglish


    • Novel polymeric
    • controlled release systems
    • biopolymers

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