Abstract
Low molecular weight chitosan was successfully used in the preparation of fairly round and spherical sustained release microspheres containing diclofenac sodium by the glutaraldehyde cross-linking of 2 % (w/v) chitosan in aqueous acetic acid solution. The stirring speed was adjusted to 1000 rpm to yield the desired size distribution of the microspheres (250-500 mu m). Some of the prepared microspheres were treated with IO or 20 % (w/w) Japan or carnauba wax solution at two different temperatures (25 and 80 or 50 and 80 degrees C), respectively, in an attempt to slow drug release and to eliminate the burst effect. Cyclohexane was used as a solvent for both Japan and carnuba wax to avoid the effect of the different types of solvents on the microspheres' characteristics. The type and concentration of wax as well as the thermal treatment of the microspheres and the pH of the dissolution medium were found to affect the rate and pattern of drug release from the microspheres.
The in vivo studies showed that treating of the microspheres with 20 % w/w Japan wax resulted in a significant increase (p < 0.05) in C-max from 9.0 +/- 1.48 to 14.3 +/- 3.85 mu g/ml, and the AUC(0-24) also increased from 63.57 +/- 12.02 to 104.63 +/- 21.25 mu g.h/ml while T-max insignificantly increased from 4.1 +/- 1.05 to 4.5 +/- 1.35 h.