FINITE DOSE PERCUTANEOUS DRUG ABSORPTION - THEORY AND ITS APPLICATION TO INVITRO TIMOLOL PERMEATION

The finite dose in vitro percutaneous absorption kinetics of timolol, a β‐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‐μm 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 μm, 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, AUC A v, and AUC A s which are the AUCs of drug amounts in vehicle and skin, respectively. The dose‐dependent skin‐timolol interaction is also discussed. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company