Linker-based lecithin microemulsions for transdermal delivery of lidocaine.
In this work, we introduce alcohol-free lecithin microemulsions formulated with linkers to produce transdermal delivery vehicles. The food-grade linker system consists of a combination of sodium caprylate and caprylic acid (hydrophilic linkers), and sorbitan monooleate (lipophilic linker). A "carrier" oil (isopropyl myristate) was used to predissolve a model lipophilic drug, lidocaine. The first part of the article describes the phase behavior and physical properties of these linker-based lecithin microemulsions. In the second part of the article, we evaluate the transdermal permeation and cytotoxicity of lidocaine formulated in oil-in-water (Type I), water-in-oil (Type II), and bicontinuous (Type IV) linker microemulsions. The transdermal permeation studies show that compared to a conventional Type II alcohol-based lecithin microemulsion, Type II linker-based microemulsions provide twice the absorption and penetration of lidocaine through skin. The larger flux obtained with linker systems is due to the presence of sodium caprylate and caprylic acid. These hydrophilic linkers accelerate the microemulsion-skin mass transfer by reducing the interfacial rigidity of the systems. Furthermore, the cytotoxicity studies show that these linker microemulsions are significantly less toxic than the alcohol-based system. The Type II linker microemulsion (containing approximately 4% lidocaine) has a comparable cytotoxicity to water saturated with lidocaine (0.4% lidocaine).
Yuan
Jessica S
JS
University of Toronto, Department of Chemical Engineering and Applied Chemistry, 200 College St., Toronto, ON, Canada M5S 3E5.
Ansari
Maham
M
Samaan
Micheline
M
Acosta
Edgar J
EJ
D000279:Administration, Cutaneous; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D002210:Caprylates / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004573:Electrolytes; D004655:Emulsions; D005079:Excipients; D006801:Humans; D054709:Lecithins; D008012:Lidocaine / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D010316:Particle Size; D000439:Pentanols / Q000737:chemistry; D012867:Skin / Q000166:cytology / Q000187:drug effects; D012869:Skin Absorption; D013552:Swine; D013696:Temperature; D013778:Tetrazolium Salts; D013844:Thiazoles; D046509:Tissue Culture Techniques; D014783:Viscosity
D000779:Anesthetics, Local; D002210:Caprylates; D004573:Electrolytes; D004655:Emulsions; D005079:Excipients; D054709:Lecithins; D000439:Pentanols; D013778:Tetrazolium Salts; D013844:Thiazoles; D008012:Lidocaine; C022616:thiazolyl blue; C031492:octanoic acid