Permeation enhancement of a highly lipophilic drug using supersaturated systems

The potential of supersaturation as a method for enhancing the membrane per meation of highly lipophilic compounds has been investigated using, as a mo del system, the transport of a lavendustin derivative (LAP, log K-o/w = 5) through silicone membrane. Propylene glycol-water mixtures, which permitted the formulation of LAP at different levels of saturation, were prepared an d tested for stability prior to conducting membrane permeation studies. The transport of LAP across silicone membrane from donor solutions containing the drug at different degrees of saturation (DS = 1-5) was evaluated by two independent experimental methods: iii using attenuated total-reflectance F ourier transform infrared spectroscopy (ATR-FTIR) and (ii) using standard v ertical diffusion cells followed by quantification with highperformance liq uid chromatography (HPLC). Both methods demonstrated a linear relationship between the DS of the applied solution and the flux through the membrane, y ielding similar values for the diffusion coefficients of LAP (diffusion cel ls, D = 1.75 (+/- 0.16) x 10(-7) cm(2) s(-1) and ATR-FTIR, D = 1.42 (+/- 0. 26) x 10(-7) cm(2) s(-1)). In addition to the characterization of LAP perme ation, ATR-FTIR spectroscopy enabled an examination of solvent transport ac ross the membrane. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutica l Association J Pharm Sci 90:607-616, 2001.