New microemulsion vehicle facilitates percutaneous penetration in vitro and cutaneous drug bioavailability in vivo.
Microemulsion systems possessing a potentially improved skin bioavailability of lidocaine were designed and explored for some characteristics. The existence of microemulsion regions was investigated in quaternary systems composed of glyceryl oleate+polyoxyl 40 fatty acid derivatives (surfactants)/tetraglycol (co-surfactant)/isopropyl palmitate/water by constructing pseudo-ternary phase diagrams at fixed co-surfactant/surfactants (CoS/S) ratios. Light scattering measurements used to determine the diameter of the internal phase revealed that lidocaine in the microemulsions increased the droplet size, implying a drug tendency to accumulate in the interfacial layers. Percutaneous penetration studies using rat skin in vitro showed that the transdermal flux of lidocaine was significantly improved by microemulsion composed of the glyceryl oleate-PEG-40 stearate combination rather than glyceryl oleate-PEG-40 hydroxylated castor oil. Two principal factors were found to govern the transdermal penetration of lidocaine from the microemulsion: water content and the CoS/S ratio. By analyzing skin layers (epidermis and dermis) for lidocaine content, significantly higher concentrations were found after rats were treated in vivo with liquid microemulsions (CoS/S=1.8, 30 wt.% water) or patches compared to those measured after application of EMLA cream. It has been suggested, therefore, that these microemulsions loaded with lidocaine would provide adequate analgesia in relatively shorter periods of time.
The Institutes for Applied Research, Ben Gurion University of the Negev, P.O. Box 653, Beer Sheva 84105, Israel. asintov@bgumail.bgu.ac.il
Amnon C
AC
Sintov
Lillia
L
Shapiro
D000279:Administration, Cutaneous; D000287:Administration, Topical; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004553:Electric Conductivity; D004655:Emulsions; D005227:Fatty Acids / Q000737:chemistry; D005989:Glycerides / Q000737:chemistry; D006018:Glycols / Q000737:chemistry; D066298:In Vitro Techniques; D008012:Lidocaine / Q000008:administration & dosage / Q000493:pharmacokinetics; D008027:Light; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D014677:Pharmaceutical Vehicles / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012542:Scattering, Radiation; D012869:Skin Absorption / Q000187:drug effects*; D012997:Solvents; D013501:Surface-Active Agents / Q000737:chemistry; D014783:Viscosity
D000779:Anesthetics, Local; D004655:Emulsions; D005227:Fatty Acids; D005989:Glycerides; D006018:Glycols; D014677:Pharmaceutical Vehicles; D012997:Solvents; D013501:Surface-Active Agents; D008012:Lidocaine; C005953:monoolein