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Concepts in Transepidermal Absorption and Penetration
Shawn Schmieder, OMS-IVParth Patel, MS-III
Joke Bouwstra, PhDKarthik Krishnamurthy, DO
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Introduction
• Absorption vs. Penetration • Barrier Properties of the Skin• Regional Variation• Physiology of Passive Transport • Enhancers of Absorption and Penetration
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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
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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.
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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
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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
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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.