The safety of chitosan as a pharmaceutical excipient.
Interest in use of the polysaccharide chitosan as a pharmaceutical excipient by different dose routes and for a number of applications is not new but it still does not appear to be present in any marketed drugs. Including a novel excipient in a new drug formulation requires a number of safety considerations. Review of the published literature showed that chitosan has low oral toxicity and local tolerance potential supporting use in non-parenteral formulations. Prior human oral exposure has occurred through use of chitosan dietary supplements and food additive, medical device and cosmetic applications. Although systemic exposure to parent chitosan may be limited (due to digestion in the gastrointestinal tract), any that is absorbed will likely undergo enzyme degradation to naturally occurring glucosamine, and N-acetylglucosamine, its copolymers, which are excreted or used in the amino sugar pool. Chitosan has local biological activity in the form of haemostatic action and, together with its ability to activate macrophages and cause cytokine stimulation (which has resulted in interest in medical device and wound healing applications), may result in a more careful assessment of its safety as a parenteral excipient.
Scientific and Regulatory Consulting, Covance Laboratories Ltd., Otley Road, Harrogate, North Yorkshire HG3 1PY, UK. paul.baldrick@covance.com
Paul
P
Baldrick
D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D005079:Excipients / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D006801:Humans; D011358:Product Surveillance, Postmarketing
D005079:Excipients; D048271:Chitosan