Dual sorption model for the nonlinear percutaneous permeation kinetics of timolol.

The nonlinear percutaneous permeation kinetics of timolol were studied in vitro with human cadaver skin. In the sorption isotherm (equilibrium) study, the plots of the amount of timolol per unit area of epidermis versus aqueous timolol concentration in equilibrium were curvilinear as the dual sorption model predicts. In the penetration study, several aqueous timolol concentrations were maintained in the donor cell for 25 h. The lag-time was prolonged as the timolol concentration in the donor cell was decreased. The change in the lag time was analyzed by a newly proposed method with the lag-time prolongation factor that is calculated from the parameter values obtained in the sorption isotherm study. The ratio of the lag-time to lag-time prolongation factor was of the same magnitude, indicating that the dual sorption model explains the nonlinear percutaneous permeation kinetics of timolol. Finally, the diffusion parameter for the mobile solute was estimated by fitting the data of the cumulative amount excreted into receptor cell versus time to the numerical solution of the dual sorption model. The observed data were roughly compatible with the values predicted by the dual sorption model.