Use of chitosan and hydroxypropylchitosan in drug formulations to effect sustained release.

Abstract

This study was an attempt to develop implantable sustained release forms of drugs, based on formulations containing chitosan, a biodegradable polymer from a natural source, and hydroxypropylchitosan (HP-chitosan), its water-soluble derivative. The possibilities were explored using uracil as a model for anticancer drugs. Enzymatic degradation of chitosan and HP-chitosan was first confirmed in vitro (using lysozyme) and in vivo by implanting both materials subcutaneously into the backs of rats. Then, using an in vitro dissolution test, we found that the release rate of uracil from chitosan membranes could be altered by the addition of HP-chitosan. Film- and stick-type implantable dosage forms of chitosan containing uracil were prepared by the 'Extrusion-in-Air' method. These gave rise to sustained release of uracil in vitro and in vivo. We conclude that chitosan and HP-chitosan have a potential as biocompatible and biodegradable vehicles in the preparation of implantable sustained release dosage forms of anticancer drugs.