New microemulsion vehicle facilitates percutaneous penetration in vitro and cutaneous drug bioavailability in vivo

• Published in: Journal of controlled release 2004-03, Vol.95 (2), p.173-183
• Main Authors: Sintov, Amnon C, Shapiro, Lillia
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Administration, Topical; Anesthetics, Local - administration & dosage; Anesthetics, Local - pharmacokinetics; Animals; Biological and medical sciences; Biological Availability; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Electric Conductivity; Emulsions; Fatty Acids - chemistry; General pharmacology; Glycerides - chemistry; Glycols - chemistry; In Vitro Techniques; Lidocaine; Lidocaine - administration & dosage; Lidocaine - pharmacokinetics; Light; Male; Medical sciences; Mice; Mice, Hairless; Microemulsion; Percutaneous penetration; Pharmaceutical technology. Pharmaceutical industry; Pharmaceutical Vehicles - chemistry; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Scattering, Radiation; Skin Absorption - drug effects; Skin permeation; Solvents; Surface-Active Agents - chemistry; Topical drug delivery; Viscosity
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2003.11.004

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.