Concepts in Transepidermal Absorption and Penetration

Shawn Schmieder, OMS-IVParth Patel, MS-III

Joke Bouwstra, PhDKarthik 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 skin2. 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 structure3. 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 *(c0 – c1) / h

1. K = partition coefficient 2. D = diffusivity3. h = membrane thickness4. c1 = concentration of substance already across the

membrane 5. c0 = 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.