Preparation and evaluation of sustained release cross-linked chitosan microspheres containing phenobarbitone

Abstract

Chitosan microspheres containing phenoharbitone were successfully prepared by glutaraldehyde cross-linking of an aqueous acetic acid dispersion of chitosan in light liquid parafin containing sorhitan mono-oleate as a stabilizing agent. Uniform and spherical microspheres, with a loading efficiency up to 57.2%., could be prepared depending on the preparation conditions. The main paramctcrs affecting the preparation and the performance of the prepared microspheres were the molecular weight and concentration of chitosan as well as thc conccntration of the used stabilizing agent. The incorporation of citric acid into the microspheres was found to increase the formation of a water-solublc gel when the microspheres come in contact with the dissolution mcdium increasing the rate of drug relcase. The particle size was shifted towards smaller diameters with increased concentration of sorbitan mono-oleate, up to 4.0%, v/v, by use of a lower concentration of chitosan (1.0% w/v) and chitosan with low molecular weight. Rapid initial drug release (20–30′%) of the incorporated drug) was exhibited in all the prepared microspheres followed by slow rclcasc of the remaining amount of the drug. The release rate of the drug from the micro-spheres prepared from high molecular weight chitosan was slow in comparison with that prepared from medium and low molecular weight chitosan. High concentrations of sorhitan mono-oleate increased the rate of drug release.

Key Words:

• Chitosan
• microspheres
• sustained-release
• cross-linked
• phenobarbitone