Transdermal delivery of naloxone: effect of water, propylene glycol, ethanol and their binary combinations on permeation through rat skin

The effect of the solvent systems water, ethanol (EtOH), propylene glycol ( PG) and their binary combinations was studied on the ex vivo permeation pro file of the opioid receptor antagonist, naloxone. through rat skin. Fourier transform-infrared (FT-IR) spectroscopic studies were done to investigate the effect of enhancers on the biophysical properties of the stratum corneu m (SC), in order to understand the mechanism of permeation enhancement of n aloxone by the solvent systems used. The flux of naloxone was found to incr ease with increasing concentrations of EtOH, upto 66% in water, and PG upto 50% in water. The maximum flux of 32.85 mug cm(-2) h (1) was found with 33 % PG in EtOH. The FT-IR spectra of SC treated with EtOH showed peak broaden ing at 2920 cm(-1) at all concentrations of EtOH studied indicating that Et OH increases the translational freedom (mobility) of lipid acyl chains. The oretical blood levels well above the therapeutic concentration of naloxone can be achieved with the solvent system comprising 33% PG in EtOH and hence , provides flexibility in choice of patch size depending on the addiction s tatus of the patient to be treated. (C) 2001 Published by Elsevier Science B.V.