Chitosan as an enabling excipient for drug delivery systems - I. Molecularmodifications

Chitosan was physicochemically modified for its potential use as a matrix f or an implantable antibiotic delivery system that could sustain bactericida l concentrations in the vicinity of an implant or prosthesis. Deacetylation and depolymerization of chitosan were implemented in order to increase the number or accessibility of the reactive amino groups on the polymer backbo ne for better polymer-drug interaction. The deacetylation process involved reaction of particulate chitosan/depolymerized chitosan with alkali. The ra te of deacetylation of chitosan was directly proportional to the reaction t emperature up to 80 degrees C; beyond 80 degrees C, rapid degradation of th e polymer occurred. The depolymerization of chitosan involved acid digestio n of the polymer followed by application of mechanical agitation. This depo lymerized product, although water insoluble, possessed a molecular weight t hat was one to two orders of magnitude lower than that of commercially avai lable chitosans. These products not only exhibited improved reactivity, but also showed increased crystallinity when compared with the parent chitosan . The reactivity was found to be inversely proportional to chitosan's molec ular weight. The depolymerization and deacetylation treatments afforded for mation of chitosan having a greater number of amino groups available for in teractions with the anionic actives. (C) 2000 Elsevier Science B.V. All rig hts reserved.