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

• Published in: Journal of pharmaceutical sciences 2011-07, Vol.100 (7), p.2989-2995
• Main Authors: Frasch, H. Frederick, Barbero, Ana M., Hettick, Justin M., Nitsche, Johannes M.
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Biological and medical sciences; Diffusion; Epidermis - metabolism; Female; General pharmacology; Humans; In Vitro Techniques; keratin; Kinetics; lag time; Linear Models; Medical sciences; Models, Biological; passive diffusion/transport; Permeability; permeable corneocytes; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Protein Binding; reversible binding; Skin Absorption; theophylline; Theophylline - administration & dosage; Theophylline - metabolism; transdermal; transient diffusion
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.22489

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 (0–2000μg/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 20.1h. 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