Thesis (Ph.D.)--Chulalongkorn University, 2003

The major objective of this study is to investigate the influence of degree of deacetylation (%DD) and molecular weight (MW) of chitosan on a release behavior of diclofenac sodium (DS) from the chitosan matrix. In addition, an effect of drug delivery vehicle design of chitosan beads with diameter in the range of 500-1000 micrometer, chitosan microparticles with mean sized diameter 37 micrometer and chitosan beads coated with multilayers thin film were also taken into consideration. Beads of chitosan with %DD of 70 and 91 and the MW of 150,000, 400,000 and 600,000 Daltons were prepared. Bead size was not affected by %DD and MW. A phosphate buffer with pH 6.8 was chosen as a media for DS release study. This condition mimics small intestinal fluid found in human digestive system. The highest DS loading efficiency was 83% and the highest DS released after 8 hr of 75%, take place at MW = 400,000 Daltons. DS releasing rate in 91%DD chitosan bead was slightly higher than that of 70%DD. The DS releasing rate increased slightly with the increase in chitosan molecular weight. Design of drug carrier plays also important role in determining the DS releasing rate. The maximum DS released after 8 hr from the chitosan bead at 75% was slightly lower than that from the chitosan microparticles at 85%. The chitosan bead coated with 3 alternating layers of alginate-chitosan-alginate, reduced the maximum DS released to only 5-39%. A solvation behavior of chitosan monomer and tetramer units in aqueous solution was studied using computer simulations, Monte Carlo (MC) and Molecular Dynamic (MD) methods. For chitosan monomer, the newly develop ab initio fitted and the force field potential yielded almost identical results. The first solvation layer was observed at a distance of 4.6 [aunstrom], with the corresponding coordination number of 7 water molecules. For the chitosan tetramer, the MD results, however, indicate that the solvation at the oxygen atom in the hydroxy and aminegroups is much higher than that at oxygen atom in the glycosidic linkage