Permeation enhancement of a highly lipophilic drug using supersaturated systems.

The potential of supersaturation as a method for enhancing the membrane permeation of highly lipophilic compounds has been investigated using, as a model 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 and 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: (i) using attenuated total-reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and (ii) using standard vertical diffusion cells followed by quantification with high-performance liquid chromatography (HPLC). Both methods demonstrated a linear relationship between the DS of the applied solution and the flux through the membrane, yielding similar values for the diffusion coefficients of LAP [diffusion cells, 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 permeation, ATR-FTIR spectroscopy enabled an examination of solvent transport across the membrane. Copyright 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association.