Concepts in Transepidermal Absorption and Penetration Shawn Schmieder, OMS-IV Parth Patel, MS-III Joke Bouwstra, PhD Karthik Krishnamurthy, DO

Introduction Absorption vs. Penetration Barrier Properties of the Skin Regional Variation Physiology of Passive Transport Enhancers of Absorption and Penetration

Accumulation/Absorption vs. Penetration The terms absorption and penetration are often used interchangeably; this is incorrect. Absorption: accumulation, the amount of substance building up in the skin over a period of time. Penetration: 1.Measure of flux or transport across the skin 2.The amount crossing the skin per unit area, per unit time

Barrier Properties of the Skin The stratum corneum is the greatest barrier to drug penetration. The stratum corneum is made up of keratinized cells with a lipid-rich extracellular space. The lipid-rich extracellular space consists of ceramides, cholesterol, free fatty acids. The enzymes that create these lipids are most active at a low pH. The low pH also serves to limit proteases that degrade corneodesmosomes.

Regional Variation Many physicians correlate skin thickness with barrier penetration. However, regional variation in penetration is primarily governed by the composition of the extracellular space in the stratum corneum. Specifically, penetration is correlated with: 1.The number of lamellar membranes (contain the enzymes necessary for converting lipids into their end products) 2.Membrane structure 3.Lipid composition: i.e. sphingomyelin:ceramide ratio

Physiology of Passive Transport Transport across stratum corneum is governed by Fick's Law because it is a "dead" layer. Fick’s law: flux = KD *(c 0 – c 1 ) / h 1.K = partition coefficient 2.D = diffusivity 3.h = membrane thickness 4.c 1 = concentration of substance already across the membrane 5.c 0 = concentration of substance applied

Enhancers of Accumulation and Penetration There are both active and passive ways to enhance penetration. This article and presentation focuses mainly on the passive methods. Passive methods include hydration, a great many chemical excipients, and nanoparticles. Some of the most studied excipients include: DMSO, azone, N-methyl-2-pyrrolidone, 2-pyrrolidone, fatty acids, ethanol, propylene glycol, urea, menthol, and essential oils.