Transdermal delivery controlled by a chitosan membrane.
The release of a drug from a transdermal delivery system with a rate controlling chitosan membrane was analyzed in vitro and in vivo. Lidocaine hydrochloride, a local anesthetic, was used as the model drug. The in vitro permeability of various chitosan membranes for the drug was investigated using a Franz diffusion cell. Drug release was slower through chitosan membranes with a higher degree of deacetylation (% DD) and with a larger thickness. A transdermal chitosan patch was developed using a chitosan membrane for rate control and a chitosan hydrogel as a drug reservoir. The most prolonged release in vitro was obtained with a 95% DD chitosan rate controlling membrane. The transport mechanism was found to be non-Fickian. The functionality of this transdermal patch was studied on the forearm of human volunteers by assessing the anesthetic effect. Patches with 70% and 95% DD membranes delayed the anesthetic effect, increasing the delay with increasing % DD. It was concluded that a combination of chitosan membrane and chitosan hydrogel is a good transparent system for controlled drug delivery and that the release kinetics in vitro at least for lidocaine have a predictive value for its anesthetic effect in vivo. The demonstration of a direct relationship between in vitro drug membrane permeability and its physiological effect might be considered as quite unique.
Thein-Han
Wah Wah
WW
Bioprocess Technology, Asian Institute of Technology, Bangkok, Thailand.
Stevens
Willem F
WF
D000279:Administration, Cutaneous; D000328:Adult; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000737:chemistry*; D002686:Chitin / Q000031:analogs & derivatives* / Q000737:chemistry*; D048271:Chitosan; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D020100:Hydrogels; D008012:Lidocaine / Q000008:administration & dosage* / Q000737:chemistry*; D008297:Male; D008567:Membranes, Artificial; D010539:Permeability; D012995:Solubility; D013678:Technology, Pharmaceutical
D000779:Anesthetics, Local; D003692:Delayed-Action Preparations; D020100:Hydrogels; D008567:Membranes, Artificial; D002686:Chitin; D048271:Chitosan; D008012:Lidocaine