Development of bioadhesive chitosan gels for topical delivery of lidocaine

Abstract

Lidocaine (LC) is a local anesthetic agent. The aim of this study is prolonging the anesthetic effect of this drug for transdermal delivery. Gels of LC hydrochloride were prepared with three different molecular weights (MW) and concentrations of chitosan. lecithin was used as permeation enhancer. Viscosity, bioadhesion, drug release from synthetic membranes, drug permeation through the biological barrier (rat skin) and antinocicetive effect of gels were studied. Increasing the concentration of chitosan caused to decrease the bioadhesion. Drug release studies in gels showed that increasing the concentration and MW of chitosan caused an increase in both the rate and extent and also in flux of drug probably because of the increase in repulsive forces between LC and chitosan cations. The flux of drug through the rat skin was higher for 3% high MW chitosan gel (H3) compared to the standard gel. LC was effective topically in hind paw formalin assay. It was most active immediately after its administration. The analgesic activity of LC in H3 gel could cover the duration of the formalin nociception. The maximal response of LC in comparable doses of H3 and standard gel was about 52% and 36% analgesia in the second phase, respectively compared to the control group. The higher response of the H3 gel may be attributed to the bioadhesive effect of chitosan base and the higher concentrations of LC compared to the standard gel. © Österreichische Apotheker-Verlagsgesellschaft m. b. H.