Original Article |
2003, Vol.25, No.2, pp. 245-254
Development of indomethacin sustained release microcapsules using chitosan-carboxymethyl-cellulose complex coacervation
Waree Tiyaboonchai and Garnpimol C. Ritthidej
pp. 245 - 254
Abstract
Indomethacin sustained release microcapsules were prepared by complex coacervation of chitosan (CS) and carboxymethylcellulose (CMC) and then were hardened with glutaraldehyde (GA). The effects of concentration and pH of CS solution, amount of GA and hardening time on the physicochemical properties and drug release of these microcapsules were investigated. The SEM photomicrographs revealed that surface morphology of microcapsules depended on the pH of CS solution. Decreasing the pH increased the smoothness of the surface due to the relaxation of CS chain in acidic medium. The geometric mean diameters of the microcapsules were between 126-212 microns. Those prepared from CS solution of pH 4 and hardening time of 3 hours seemed to have the narrowest size distribution. The percent drug entrapment was comparable in the range of 40%-50% while the percent drug recovery varied between 60%-87%. The latter increased when decreasing the pH and increasing the concentration of CS solution but decreased when increasing the hardening time. Dissolution study showed that microcapsules prepared from CS solution of high pH initially released the drug faster than those from CS solution of lower pH. After 3 hours their release rate was similar. Increasing the amount of GA and hardening time decreased the drug release due to denser membrane. In contrast, the concentration of CS solution had no effect on drug release. The mechanism of drug release was prominently diffusion controlled through wall membrane and pore. The kinetics of drug release followed Higuchi’s model.