Tissue Binding Affects the Kinetics of Theophylline Diffusion Through the Stratum Corneum Barrier Layer of Skin

New data sets on both (i) equilibrium theophylline (TH) partitioning/binding in stratum corneum and (ii) transient TH diffusion through human epidermis are explained by an extended partition-diffusion model with reversible binding. Data conform to a linear binding isotherm within the tested concentration range (0-2000 μg/mL) with an equilibrium ratio of bound-to-free solute of approximately 1.4. The permeability coefficient for TH is 4.86 × 10−5 cm/h, and the lag time is 20.1 h. Binding occurs as a slow process, significantly affecting the kinetics of dermal penetration. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:2989-2995, 2011