title: Enhanced local anesthetic action of mepivacaine from the bioadhesive gels.
abstract: Mepivacaine, an amide-type local anesthetic, has been used to relieve local pain. Among the many drug delivery systems, transdermal drug delivery has some advantages, as it provides controlled drug delivery for an extended period of time. To develop new gel formulations that have suitable bioadhesion, the bioadhesive force of hydroxypropyl methylcellulose (HPMC) was assessed using an auto-peeling tester. The effect of drug concentration on drug release from 2% HPMC gel was studied using synthetic cellulose membrane at 37±0.5°C. The drug concentrations tested were 0.5, 1, 1.5, 2, and 2.5%. The effect of temperature on drug release from the 2% drug gel was evaluated at 27, 32, 37 and 42°C. To increase the skin permeation of mepivacaine from HPMC gel, enhancers such as saturated and unsaturated fatty acids, pyrrolidones, propylene glycol derivatives, glycerides, and non-ionic surfactants were incorporated into the mepivacaine-HPMC gels. The enhancing effect of the enhancer on drug permeation was then examined in the modified Keshary-Chien cell. For the efficacy study, the anesthetic action of the formulated mepivacaine gel containing enhancer and vasoconstrictor was evaluated with the tail-flick analgesimeter. Among the various kinds of HPMC, HPMC-K100M gel showed the highest viscosity and bioadhesive force. As the viscosity of the HPMC gels increased, the bioadhesive forces increased. Increasing the drug concentration or temperature increased the drug release rate. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the greatest enhancement of permeation. Based on the area under the efficacy curve of the rat tail flick test curve, mepivacaine gel containing polyoxyethylene 2-oleyl ether and tetrahydrozoline showed prolonged and increased local anesthetic action compared to the control. For bioadhesive mepivacaine gels with enhanced local anesthetic action, mepivacaine gels containing penetration enhancer and vasoconstrictor could be developed with the bioadhesive polymer, HPMC.
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Korea.
authors.forename: Cheong-Weon
authors.initials: CW
authors.lastname: Cho
authors.forename: Jun-Shik
authors.initials: JS
authors.lastname: Choi
authors.forename: Sang-Chul
authors.initials: SC
authors.lastname: Shin
mesh_terms: D000269:Adhesives; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D005227:Fatty Acids / Q000494:pharmacology; D005782:Gels; D065347:Hypromellose Derivatives; D066298:In Vitro Techniques; D008297:Male; D008567:Membranes, Artificial; D008619:Mepivacaine / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D008747:Methylcellulose / Q000031:analogs & derivatives; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012867:Skin / Q000187:drug effects; D012869:Skin Absorption / Q000187:drug effects; D013501:Surface-Active Agents / Q000494:pharmacology; D013696:Temperature; D014783:Viscosity
chemical_list: D000269:Adhesives; D000779:Anesthetics, Local; D005227:Fatty Acids; D005782:Gels; D008567:Membranes, Artificial; D013501:Surface-Active Agents; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D008619:Mepivacaine