Controlled drug release from multi-phase polymeric particles.
Lee, Wei Li.
Date of Issue2012
School of Materials Science and Engineering
The study of the fabrication of multi-phase particles (i.e. double-layered ternary-phase microparticles, triple-layered and quadruple-layered microparticles) and their drug release profiles is reported in this thesis. The overall objective is to investigate the use of multi-phase/multi-layered microparticles with different morphologies and layer configurations as a means to control and fine-tune the drug release profiles. The results obtained show conclusive evidence that different microparticle configurations (i.e. polymer distribution and dimensions) can be achieved through the manipulation of process parameters in a one-step solvent evaporation technique. A starting polymer solution prepared below the cloud point, low stirring speed and an increased oil-to-water ratio facilitated the polymers to configure themselves towards thermodynamic equilibrium configurations. A considerably high polymer precipitation rate was needed to kinetically trap the triple-layered structure when the polymer solution was prepared above cloud point. Layer thickness and configuration were altered by changing the polymer mass ratios. Drugs can be localized within specific layers of the microparticles. A correlation of these process parameters to the final particle morphology was thus established. The ternary-phase and triple-layered microparticles were observed to provide unique and better controlled drug release as compared to single-layered and double-layered microparticles. This was due to their distinctive structural attributes and degradation behaviors of the multiple-polymer system. Drug release profiles can be further altered by changing the physicochemical properties of each polymer phase. A modeled relationship between the physicochemical processes and drug release was established for triple-layered microparticles of different layer thicknesses and particle sizes. It is concluded that the multi-phase/multi-layered microparticles can be used to better control the drug release profiles and kinetics.