|dc.description.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.||en_US