Dermal pharmacokinetics of microemulsion formulations determined by in vivo microdialysis.
OBJECTIVE
To investigate the potential of improving dermal drug delivery of hydrophilic and lipophilic substances by formulation in microemulsion vehicles and to establish a reliable pharmacokinetic model to analyze cutaneous microdialysis data.


METHODS
After a topical application of microemulsions, commercially available creams, and a hydrogel, unbound cutaneous concentrations of lidocaine and prilocaine were determined by in vivo microdialysis in rats. Recovery was monitored during the experiments via retrodialysis by calibrator.


RESULTS
The presented pharmacokinetic model provided an excellent fit of the microdialysis concentration-time curves with reliable estimation of absorption coefficient and lag time. The microemulsion formulations were shown to increase the absorption coefficient of lidocaine more than eight times (753 microg/l/min) compared with a conventional oil-in-water emulsion-based cream (89 microg/l/min) and prilocaine hydrochloride almost two times (8.9 microg/l/min) compared with hydrogel (5.2 microg/l/min).


CONCLUSIONS
The microemulsion formulations can be applied to increase dermal drug delivery of both the hydrophilic and lipophilic model drug. The pharmacokinetic model presented in this report is, to the author's knowledge, the first example in the literature, providing reliable estimation of cutaneous absorption coefficient and lag time from microdialysis data of topically applied substances.
Kreilgaard
M
M
The Royal Danish School of Pharmacy, Department of Pharmaceutics, Copenhagen. makr@lundbeck.com
D000287:Administration, Topical; D000465:Algorithms; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D004655:Emulsions / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008297:Male; D017551:Microdialysis / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012869:Skin Absorption
D004655:Emulsions