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 vehi cles. Self-diffusion coefficients determined by pulsed-gradient spin-echo N MR spectroscopy and T-1 relaxation times were used to characterise the micr oemulsions. Transdermal flux of lidocaine and prilocaine hydrochloride thro ugh rat skin was determined in vitro using Franz-type diffusion cells. The formulation constituents enabled a broad variety of microemulsion compositi ons, which ranged from water-continuous to oil-continuous aggregates over p ossible bicontinuous structures, with excellent solubility properties for b oth lipophilic and hydrophilic compounds. The microemulsions increased tran sdermal flux of lidocaine up to four times compared to a conventional oil-i n-water emulsion, and that of prilocaine hydrochloride almost 10 times comp ared to a hydrogel. A correlation between self-diffusion of the drugs in th e vehicles and transdermal flux was indicated. The increased transdermal dr ug delivery from microemulsion formulations was found to be due mainly to t he increased solubility of drugs and appeared to be dependent on the drug m obility in the individual vehicle. The microemulsions did not perturb the s kin barrier, indicating a low skin irritancy. (C) 2000 Elsevier Science B.V . All rights reserved.