title: Enhanced percutaneous permeability of diclofenac using a new U-type dilutable microemulsion.
abstract: Enhanced systemic absorption in vivo and percutaneous penetration in vitro was demonstrated after transdermal administration of diclofenac sodium formulated in U-type microemulsion. Diclofenac sodium was solubilized in a typical four-component system consisting of an oil, polyoxyethylene-10EO-oleyl alcohol (Brij 96V) as the surfactant, and 1-hexanol along water dilution line W46 (40 wt % surfactant and 60 wt % oil phase before water titration). Viscosity and small angle X-ray scattering measurements have evidenced bicontinuous structures within water fractions of 0.25 and 0.5 along the dilution line. Self-diffusion NMR studies showed that drug molecules accumulated in the interfacial film and, to some extent, dissolved in the oil. Relative to a commercial macro-emulsion cream (Voltaren Emulgel), microemulsions containing paraffin oil or isopropyl myristate increased the in vivo transdermal penetration rate of diclofenac by two order of magnitude, whereas the rat plasma levels were increased by one order of magnitude. The in vitro data obtained from excised rat skin were comparable to the in vivo results, but suffered from discrepancies from the ideal in vivo-in vitro correlation, which might be explained by optimal in vitro conditions of perfusion and hydration. It has also been found that when jojoba oil is formulated as the oil phase in the microemulsion, the penetration rate of the drug decreases significantly. Based on the three-dimensional structure of jojoba oil, the wax is presumed to prevent the drug from being freely diffused into the skin while migrating from the interfacial film into the continuous oil phase.
authors.affiliation: Department of Chemistry, Faculty of Natural Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Marina
authors.initials: M
authors.lastname: Shevachman
authors.forename: Nissim
authors.initials: N
authors.lastname: Garti
authors.forename: Arnon
authors.initials: A
authors.lastname: Shani
authors.forename: Amnon C
authors.initials: AC
authors.lastname: Sintov
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D004008:Diclofenac / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004655:Emulsions; D005079:Excipients / Q000737:chemistry*; D000441:Hexanols / Q000737:chemistry; D008297:Male; D009226:Myristates / Q000737:chemistry; D009821:Oils / Q000737:chemistry; D010232:Paraffin / Q000737:chemistry; D010539:Permeability; D010938:Plant Oils / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D014783:Viscosity; D014885:Waxes / Q000737:chemistry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004655:Emulsions; D005079:Excipients; D000441:Hexanols; D009226:Myristates; D009821:Oils; D010938:Plant Oils; D013501:Surface-Active Agents; D014885:Waxes; C008205:isopropyl myristate; D004008:Diclofenac; D011092:Polyethylene Glycols; C036260:1-hexanol; C034743:jojoba wax; D010232:Paraffin; C015418:paraffin oils; C033084:polyethylene glycol oleyl ether