Finite dose percutaneous drug absorption: theory and its application to in vitro timolol permeation

The finite dose in vitro percutaneous absorption kinetics of timolol, a beta-blocker, was studied. The flux of timolol across excised human abdominal cadaver skin was measured over a period of 72 h following application of a 40-microns thickness patch containing 5, 10, or 20% (w/v) timolol free base. Amounts of timolol in the patch and skin were also determined at 6, 12, 24, 48, and 72 h after the application of the 20% (w/v) patch. The mean diffusion and partition parameters were estimated to be 0.018 h-1 and 125.9 microns, respectively, using a newly developed theory. Diffusion and partition parameters were estimated using the values for amounts of a drug eventually partitioning into the perfusing water, as well as two newly proposed conceptual parameter values, AUCAv and AUCAs which are the AUCs of drug amounts in vehicle and skin, respectively. The dose-dependent skin-timolol interaction is also discussed.