A proposed new method for the crosslinking of chitosan microspheres

This work concerns microparticulate drug delivery systems based on the natural polymer, chitosan. A new method for the chemical crosslinking of spray-dried chitosan microspheres containing cetylpyridinium chloride (CPC), as a model of an amphiphilic drug, is here proposed and evaluated. The method consists of the exposure of spray-dried microspheres to the vapor of crosslinking agents that act in gaseous phase and under mild conditions. The novelty and the major advantage of the proposed method is that it does not involve liquid phases coming in contact with the microspheres and in which the drug could dissolve. Three different chemical crosslinking agents, glutaraldehyde, epichlorohydrin, and glyceraldehyde, have been used to evaluate the feasibility of the method. The microparticulate drug delivery systems prepared could find useful pharmaceutical applications as disinfectants and healing powders. The results obtained show that the crosslinking process is effective in promoting modulation of drug release rate from the microspheres. Glyceraldehyde appears to be a good crosslinking agent with the advantage of being nontoxic.