NMR characterisation and transdermal drug delivery potential of microemulsion systems.
The purpose of this study was to investigate the influence of structure and composition of microemulsions (Labrasol/Plurol Isostearique/isostearylic isostearate/water) on their transdermal delivery potential of a lipophilic (lidocaine) and a hydrophilic model drug (prilocaine hydrochloride), and to compare the drug delivery potential of microemulsions to conventional vehicles. Self-diffusion coefficients determined by pulsed-gradient spin-echo NMR spectroscopy and T(1) relaxation times were used to characterise the microemulsions. Transdermal flux of lidocaine and prilocaine hydrochloride through rat skin was determined in vitro using Franz-type diffusion cells. The formulation constituents enabled a broad variety of microemulsion compositions, which ranged from water-continuous to oil-continuous aggregates over possible bicontinuous structures, with excellent solubility properties for both lipophilic and hydrophilic compounds. The microemulsions increased transdermal flux of lidocaine up to four times compared to a conventional oil-in-water emulsion, and that of prilocaine hydrochloride almost 10 times compared to a hydrogel. A correlation between self-diffusion of the drugs in the vehicles and transdermal flux was indicated. The increased transdermal drug delivery from microemulsion formulations was found to be due mainly to the increased solubility of drugs and appeared to be dependent on the drug mobility in the individual vehicle. The microemulsions did not perturb the skin barrier, indicating a low skin irritancy.
Kreilgaard
M
M
Department of Pharmaceutics, The Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100, Copenhagen, Denmark. makr@lundbeck.com
Pedersen
E J
EJ
Jaroszewski
J W
JW
D000279:Administration, Cutaneous; D000818:Animals; D004058:Diffusion; D004655:Emulsions; D007509:Irritants / Q000633:toxicity; D008012:Lidocaine / Q000008:administration & dosage / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D014677:Pharmaceutical Vehicles; D011318:Prilocaine / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012995:Solubility
D004655:Emulsions; D007509:Irritants; D014677:Pharmaceutical Vehicles; D011318:Prilocaine; D008012:Lidocaine