เฉลิมพล เหลืองหิรัญ. Modeling of a Controlled-release Drug Delivery System . Master's Degree(Chemical Engineering). King Mongkut's University of Technology Thonburi. : King Mongkut's University of Technology Thonburi, 2005.
Modeling of a Controlled-release Drug Delivery System
Abstract:
A controlled-release drug delivery system is used to control the concentration and the
release time of a chemotherapy drug in cancer patients. After surgery, either
radiofrequency or chemotherapy is used to destroy the remaining tumor tissue. A
mathematical model of a controlled-release drug delivery system was developed to
help researchers design controlled release experiments before using this system in
cancer patients. The use of this mathematical model can effectively reduce the cost of
the experiments, and save time in performing experiments. In this study, doxorubicin
was chosen as a model anticancer drug, while pluronic was selected as a polymeric
device to control the release of the drug. To develop a mathematical model, some
important parameters and correlations such as the gel dissolution constants and the
ratio of gel dissolved and drug release were determined. The predictions from the
model were compared with the experimental results which consisted of various
combinations of pluronic gel concentrations (20 30 percents) and doxorubicin
concentrations (100?g 200?g per loading). The predictions from the model matched
with the experimental results quite well with the average percentage error of less than
8.38 percents. Afterwards, the polymer dissolution constants and the correlation of
percentage gel dissolved and percentage drug release were added to FEMLAB 3.0
simulation program to study the effect of various gel geometries on the drug release
kinetics. A step function was used to solve a moving interfacial boundary problem
between the polymer and the medium solution. In a two-dimensional gel structure, the
diffusion coefficient as a function of concentration was determined. The simulation
results were somewhat consistent with the experimental results. The last part of this
thesis work focuses on the application of this mathematical model to predict the
release of doxorubicin from Pluronic gel inside a rabbit brain. We found that
doxorubicin was distributed non-uniformly due to the flow direction of the brain
interstitial fluid and that the drug distribution profiles were different depending on the
polymer implant location.