Enhanced permeation of fentanyl from supersaturated solutions in a model membrane

The aim of the present study was to investigate the permeation of fentanyl from supersaturated formulations when applied to silicone membrane. Silicone was chosen in order to separate the effects of supersaturation from other possible influences of volatile formulation components on biological membranes. Supersaturated formulations containing either propylene glycol/water (PG/H(2)O) or propylene glycol/ethanol (PG/Et) were prepared containing varying degrees of saturation (DS) of fentanyl. Permeation of finite and infinite doses of the PG/H(2)O formulations, and finite doses of the PG/Et formulations was investigated using Franz-type diffusion cells. For the PG/H(2)O formulations a good correlation between the flux and the DS of the formulation up to 5 DS for infinite dose studies (r(2)=0.99), and up to 7 DS for finite dose studies (r(2)=0.98), was evident. Similarly, for the PG/Et formulations there is a good correlation between the mean flux and the theoretical DS of the formulation (r(2)=0.95). Except for the 2 DS formulations, no significant differences were seen in the mean flux between PG/H(2)O and PG/Et finite dose studies. The larger fluxes observed for infinite doses of the PG/H(2)O formulations versus finite doses reflect changes in the effective area of diffusion over the time of the experiment for the latter set of experiments. The permeation enhancement observed for PG/Et formulations confirms that enhanced drug thermodynamic activity was induced by ethanol evaporation.