Design And Tailoring Of Crosslinked Acrylic Polymers For Drug Controlled Release

Controlled release systems (CRS) have been widely used in many applications, such as pharmacy, pesticide, fertilizer, catalyst, cosmetic, etc. Owing to advantages in improving drug effectiveness, reducing toxicity and side-effects, and having better patient compliance, the CRSs have attracted more attention in drug applications. Among the CRSs, diffusion-controlled polymeric matrixes are most widely used, mainly because of their low manufacturing costs and easy fabrication. The studies on the diffusion-controlled release systems will greatly benefit for new drug development.In this work, a mathematical model was developed to describe the drug release behavior in diffusion-controlled matrix systems. A mixed Newton-Tikhonov regularization method was applied to optimize the initial drug concentration and diffusivity profiles in slab and sphere matrix systems for different targeted release profiles. The results show that initial concentration profiles in the CRSs with a constant diffusivity could be optimized to achieve a constant, linearly decreased or non-linear (linearly increased followed by a constant release) release. The drug releases from the CRSs having various initial concentration distributions could also reach a nearly constant release by optimization of their diffusivity distributions. A simple non-uniform initial concentration distribution with none or extremely low concentration in the outer layer of the CRSs had highly potential to minimize’burst effect’.With the aid of modeling results, polymeric matrix devices having diffusivity distributions were designed and tailored. A series of crosslinked poly(butyl acrylate)(PBA) slabs were prepared by reversible addition-fragmentation chain transfer (RAFT) copolymerization of BA with EGDMA. A lipophilic dye of (4-aminoazobenzene) was used as a model drug system. The dye releases in the PBA slab systems were studied. It was found that the diffusivities in the PBA slabs decreased monotonously with the PBA crosslink densities, indicating a tailored diffusivity in a polymeric matrix system could be achieved by controlling the crosslink density. Moreover, a two-layer PBA slab system with different crosslink densities was designed and constructed. The experimental dye release data from the two-layer system agreed well with theoretical predictions. The design and tailoring of multilayer polymer matrixes with controlled crosslink densities turn to be an effective approach to achieve a targeted control release performance.The innovation in this work is summarized as follows:1). the release behaviors in diffusion-controlled matrix systems were systematically studied by mathematical model. The optimization of initial concentration and diffusivity profiles further directed the design and construction of CRSs.2). a novel approach of tailoring the CRSs with diffusivity distributions by controlling crosslink densities in polymers via RAFT copolymerization was developed.