Berchane, Nader Samir (2007-12). Experimental and computational investigations of therapeutic drug release from biodegradable poly(lactide-co-glycolide) (plg) microspheres. Doctoral Dissertation. Thesis uri icon

abstract

  • The need to tailor release-rate profiles from polymeric microspheres remains one of the leading challenges in controlled drug delivery. Microsphere size, which has a significant effect on drug release rate, can potentially be varied to design a controlled drug delivery system with desired release profile. In addition, drug release rate from polymeric microspheres is dependent on material properties such as polymer molecular weight. Mathematical modeling provides insight into the fundamental processes that govern the release, and once validated with experimental results, it can be used to tailor a desired controlled drug delivery system. To these ends, PLG microspheres were fabricated using the oil-in-water emulsion technique. A quantitative study that describes the size distribution of poly(lactide-coglycolide) (PLG) microspheres is presented. A fluid mechanics-based correlation that predicts the mean microsphere diameter is formulated based on the theory of emulsification in turbulent flow. The effects of microspheres' mean diameter, polydispersity, and polymer molecular weight on therapeutic drug release rate from poly(lactide-co-glycolide) (PLG) microspheres were investigated experimentally. Based on the experimental results, a suitable mathematical theory has been developed that incorporates the effect of microsphere size distribution and polymer degradation on drug release. In addition, a numerical optimization technique, based on the least squares method, was developed to achieve desired therapeutic drug release profiles by combining individual microsphere populations. The fluid mechanics-based mathematical correlation that predicts microsphere mean diameter provided a close fit to the experimental results. We show from in vitro release experiments that microsphere size has a significant effect on drug release rate. The initial release rate decreased with an increase in microsphere size. In addition, the release profile changed from first order to concave-upward (sigmoidal) as the microsphere size was increased. The mathematical model gave a good fit to the experimental release data. Using the numerical optimization technique, it was possible to achieve desired release profiles, in particular zero-order and pulsatile release, by combining individual microsphere populations at the appropriate proportions. Overall, this work shows that engineering polymeric microsphere populations having predetermined characteristics is an effective means to obtain desired therapeutic drug release patterns, relevant for controlled drug delivery.
  • The need to tailor release-rate profiles from polymeric microspheres remains one of
    the leading challenges in controlled drug delivery. Microsphere size, which has a
    significant effect on drug release rate, can potentially be varied to design a controlled
    drug delivery system with desired release profile. In addition, drug release rate from
    polymeric microspheres is dependent on material properties such as polymer molecular
    weight. Mathematical modeling provides insight into the fundamental processes that
    govern the release, and once validated with experimental results, it can be used to tailor a
    desired controlled drug delivery system.
    To these ends, PLG microspheres were fabricated using the oil-in-water emulsion
    technique. A quantitative study that describes the size distribution of poly(lactide-coglycolide)
    (PLG) microspheres is presented. A fluid mechanics-based correlation that
    predicts the mean microsphere diameter is formulated based on the theory of
    emulsification in turbulent flow. The effects of microspheres' mean diameter,
    polydispersity, and polymer molecular weight on therapeutic drug release rate from poly(lactide-co-glycolide) (PLG) microspheres were investigated experimentally. Based
    on the experimental results, a suitable mathematical theory has been developed that
    incorporates the effect of microsphere size distribution and polymer degradation on drug
    release. In addition, a numerical optimization technique, based on the least squares
    method, was developed to achieve desired therapeutic drug release profiles by
    combining individual microsphere populations.
    The fluid mechanics-based mathematical correlation that predicts microsphere mean
    diameter provided a close fit to the experimental results. We show from in vitro release
    experiments that microsphere size has a significant effect on drug release rate. The initial
    release rate decreased with an increase in microsphere size. In addition, the release
    profile changed from first order to concave-upward (sigmoidal) as the microsphere size
    was increased. The mathematical model gave a good fit to the experimental release data.
    Using the numerical optimization technique, it was possible to achieve desired release
    profiles, in particular zero-order and pulsatile release, by combining individual
    microsphere populations at the appropriate proportions.
    Overall, this work shows that engineering polymeric microsphere populations having
    predetermined characteristics is an effective means to obtain desired therapeutic drug
    release patterns, relevant for controlled drug delivery.

publication date

  • December 2007