Facilitated skin penetration of lidocaine: combination of a short-term iontophoresis and microemulsion formulation.
The objective of this study was to demonstrate the potential of the application of a short-term iontophoresis on the topical delivery of lidocaine hydrochloride from a microemulsion-based system. Five- and 10-min durations of anodal iontophoresis applied onto porcine skin were examined in combination with a microemulsion containing 2.5% lidocaine hydrochloride. A similar combination (10-min iontophoresis with microemulsion in the anodal electrode) was also examined in vivo in a rat model. It was shown in vitro that by combining microemulsion application with a 10-min iontophoresis of 1.13 mA/cm2 electric current density, a significantly increased flux was obtained compared with a combination of aqueous drug solution with the same iontophoresis protocol. In vivo studies revealed that 57.71 +/- 18.65 and 18.43 +/- 9.17 microg cm(-2) were reached in the epidermis and dermis, respectively, at t = 30 min of microemulsion application, when iontophoresis was applied for 10 min. In contrast, the application of aqueous solution-iontophoresis resulted in a relatively lower drug accumulation (21.44 +/- 10.42 and 5.30 +/- 2.25 microg cm(-2) in the epidermis and dermis, respectively, at t = 30) with more rapid clearance of the drug from the skin. Ten-minute application of a low-current electric field on a new topical microemulsion appears to make significant changes in skin permeability. The potential advantages of this procedure include significantly increased flux, accumulation of a large skin drug depot, short lag times, reduced irritation (compared to long-term iontophoresis), simplicity and ease of compliance.
Sintov
Amnon C
AC
Department of Pharmacology and School of Pharmacy, E. D. Bergmann Campus, Ben Gurion University of the Negev, P.O. Box 653, Beer Sheva 84105, Israel. asintov@bgu.ac.il
Brandys-Sitton
Roy
R
D000779:Anesthetics, Local / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D004339:Drug Compounding; D004655:Emulsions; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007478:Iontophoresis; D008012:Lidocaine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D012879:Skin Physiological Phenomena; D013552:Swine; D013997:Time Factors
D000779:Anesthetics, Local; D004337:Drug Carriers; D004655:Emulsions; D008012:Lidocaine