Effect of cross-linking on physicochemical properties of chitosan mucoadhesive microspheres: A factorial approach

Abstract

The objective of the present study was to develop chitosan-based mucoadhesive microspheres of Clarithromycin, to provide a prolonged contact time for drug delivery of antibiotics, to treat stomach ulcers. Chitosan mucoadhesive microspheres with small particle size and good sphericity were prepared by an emulsification technique using glutaraldehyde as a cross linking agent. Glutaraldehyde, the aldehyde most frequently employed as a chemical cross linker agent for proteins, was also used as a control. The prepared microspheres were optimized by 32 factorial design, using the concentration of the cross linking agent (X1) and time of cross linking (X2) with respect to their morphological aspects, percentage entrapment, in-vitro drug release and percentage mucoadhesion. Microspheres were discrete, spherical and free flowing. The microspheres exhibited a good mucoadhesive property in the in vitro wash-off test and also showed a high percentage of drug entrapment efficiency. The best batch exhibited a high drug entrapment efficiency of 45% and percentage mucoadhesion after 5 hours was 15%. The drug release from microspheres was characterized by the initial burst effect followed by sustained release for more than 12 hours. It was concluded that drug entrapment efficiency was increased with an increase in glutaraldehyde concentration and an increase in cross linking time. As the glutaraldehyde concentration and cross linking time increased, the percentage of mucoadhesion decreased. Thus chitosan microspheres appeared to be, technically, promising mucoadhesive drug delivery systems for delivering Clarithromycin, to treat stomach ulcers. Key words: Chitosan, clarithromycin, cross linking, factorial design, glutaraldehyde, mucoadhesive microspheres