Transdermal delivery of naloxone: ex vivo permeation studies

The purpose of this investigation was to study the feasibility of transdermal drug delivery of the potent opioid antagonist naloxone. The pharmacokinetic profile of naloxone makes it a suitable candidate for transdermal delivery. Ex vivo permeation of naloxone through excised rat skin was studied using a diffusion cell. Radiochemical assay of drug concentration and the use of rat as an animal model were adopted in this study. Naloxone possesses characteristics favorable to percutaneous absorption: i.e. a low molecular weight (327.37), water solubility and a good lipid-water partition coefficient of 12.94 +/- 1.29 at pH 7.4. The flux (mu g/cm(2)/h) values varied from 6.59 +/- 0.72 in control to 27.18 +/- 4.26 in dimethyl formamide. The affinity of naloxone to skin in the presence of propylene glycol was decreased by 6.2 times compared to the control. Fourier transform infrared spectroscopy was used to study the effect of various sorption promoters on intercellular lipid pathways in skin. A change in lipid fluidization corresponding to broadening for both C-H symmetric (near 2850 cm(-1)) and C-H asymmetric (near 2920 cm(-1)) stretching was observed. An attempt was made to correlate the molecular weight of sorption promoters with skin affinity values of naloxone. (C) 1999 Elsevier Science B.V. All rights reserved.