(366c) Problems in Dermal Absorption As Vehicles for Teaching Diffusion and Mass Transfer

Quantitative understanding of molecular diffusion through the skin is crucial to the effective development of topically applied and transdermally delivered drugs, as well as the assessment of risks associated with chemical exposures.  Theoretical models of dermal absorption¹ can strongly support advancement in these areas by providing mechanistic insights into solute flux pathways, reasonable predictions of transdermal transport rates and subsurface concentration levels, and a quantitative framework to correlate experimental data and guide measurements.  The strong barrier properties of skin (physiologically advantageous) are precisely what make it hard to effect transdermal delivery.  So difficult is the challenge that some authors ask whether breaching the barrier is effectively holding up a crucially important avenue of pharmaceutical development, i.e., “is delivery technology keeping up?”²  Assessments for contact allergy and other elements of dermal risk must go forward in the face of increasing prohibitions on animal testing.³  Fundamental predictive understanding of molecular diffusion through the multiphase, multiscale architecture of skin lies at the core of meeting these challenges, and it represents an area where chemical engineers can make important contributions to the pharmaceutical enterprise.

More or less idealized presentations of dermal absorption problems present good opportunities to teach a variety of aspects of mass transfer in a context that makes their practical significance very tangible.  Among them are transient diffusion through effectively infinite- and finite-thickness membranes, hindered diffusion through media with fibrous and other types of microstructure, homogenization/coarse-graining of transport equations, partitioning equilibria at phase boundaries, electrostatic effects on transport, and techniques for solving differential equations.  These areas are ones in which Prof. William Deen has made seminal advances in research, both on fundamental problems and applications to renal physiology, and has empowered several academic generations of grateful students as a classroom teacher and academic mentor.

This talk describes the use of dermal absorption problems as teaching vehicles in undergraduate and graduate transport courses at the University at Buffalo.  It presents a series of examples of increasing complexity, emphasizing mechanistic understanding and the value of analytical methods.  Important lessons learned from Prof. Deen are identified for each.

1. Mitragotri S, Anissimov YG, Bunge AL, Frasch HF, Guy RH, Hadgraft J, Kasting GB, Lane ME, Roberts MS 2011. Mathematical models of skin permeability: an overview. Int J Pharm  418(1):115-129.

2. Cross SE, Roberts MS 2004. Physical enhancement of transdermal drug application: is delivery technology keeping up with pharmaceutical development? Curr Drug Deliv  1(1):81–92.

3. Basketter D, Pease C, Kasting G, Kimber I, Casati S, Cronin M, Diembeck W, Gerberick F, Hadgraft J, Hartung T, Marty JP, Nikolaidis E, Patlewicz G, Roberts D, Roggen E, Rovida C, van de Sandt J 2007. Skin sensitisation and epidermal disposition: The relevance of epidermal disposition for sensitisation hazard identification and risk assessment - The report and recommendations of ECVAM Workshop 59. Altern Lab Anim  35(1):137-154.