OPTIMIZATION OF THE FORMULATION DESIGN OF CHITOSAN MICROSPHERES CONTAINING CISPLATIN

This study describes an orthogonal experimental design to optimize the formulation of cisplatin (CDDP)-loaded chitosan microspheres (namely, CDDP-DAG-MS) which were produced by an emulsion-chemical cross-linkin g technique. Seven factors and three levels for each factor that might affect the formulation of microspheres were selected and arranged in an L(27)(3(13)) orthogonal experimental table. A desirability function (d(j)) calculated according to the trapping efficiency of CDDP, the d rug content (%, w/w), and the size distribution of each batch of micro spheres was introduced as an index of the microsphere formulation. The overall desirability functions (DF) were produced and treated by a st atistic analytical system to optimize the formulation. Moreover, the c ontour maps were produced to analyze the influence of the seven factor s on the size distribution, the drug content, and the drug trapping ef ficiency. The established optimum procedure was reproducible. Scanning electron micrographs showed that CDDP-DAC-MS were spherical with a co arse surface. The average diameter, drug content, and drug trapping ef ficiency of CDDP-DAC-MS were 74.8 mu m, 20.8% (w/w), and 77.5%, respec tively. The in vitro release of cisplatin from chitosan microspheres i n saline was retarded compared with that from saline solution; the rel ease of CDDP from chitosan microspheres was suggested to be controlled by the dissolution and diffusion of the drug from the chitosan matrix .