Modeling and design of controlled drug release systems

The design and production of controlled drug release systems (drug loaded polymer-based matrices) have become an important scientific and technological research topic. The purpose of these systems is to maintain the drug concentration within the therapeutic range for a desired period of time at a specific location. The use of this type of drug release system has several advantages over conventional drugs. Releasing drug molecules in a controlled manner allows us to maintain the drug concentrations within therapeutic range over extended periods, to diminish side effects caused by concentration extremes and repeated administrations, and to improve patient compliance. In spite of these potentials, the use of controlled drug release systems is limited due to lack of comprehensive understanding on the release kinetics. The release kinetics of the system depends on the metabolism rate of the patient, the type of the polymer loaded with drug (pore structure, degree of crystallization, molecular weight, rate of hydrolysis, diffusion coefficient of water and drug, etc.) and geometry. Within the scope of this thesis, the four main mechanisms of the drug release systems, which are the diffusion of drug molecules into the drug release system, hydrolysis of the bonds between drug molecules and the polymer matrix, diffusion of freed drug molecules within the polymer matrix and their release to the plasma, have been described/modeled with the differential equations and appropriate boundary conditions. These differential equations were solved in 3D space with various numerical methods and a simulation program was developed. To understand the relative importance of various kinetic parameters numerous simulations have been carried out and the effect of different system parameters have been investigated. These results allow us to generate ternary diagrams among four main mechanisms. These ternary diagrams provide us to design the geometry and determine the initial drug load for a given set of drug-polymer matrix systems to sustain the desired therapeutic periods with reduced side effects. Keywords: Controlled drug release systems, Modelling, Diffusion, Ternary diagrams, Simulation.