Occlusion enhances skin hydration and increases percutaneous absorption of applied substances with exception. On the other hand, it may also increase the penetration of irritants and/or antigens entering into skin and hence may increase irritant and allergic contact dermatitis. Additionally, occlusion compromises skin barrier function by impairing passive transepidermal water loss (TEWL) at the application site, and hence aggravates the irritant effect of applied compounds.
Transdermal drug delivery systems (TDDS) are typically occlusive patches placed on the skin surface for 1-7 days while delivering drugs into the systemic circulation and have been extensively investigated because of potential advantages over oral and other administration routes. However, local reactions (i.e., irritation and/or sensitization) have become obstacles in the design and application of TDDS in clinic situations.
Skin and Effects of Occlusion
Skin envelops the body surface as a flexible shield, acting as a two-way barrier, minimizing water loss, electrolytes, and other body constituents and decreasing the entry of noxious substances from the external environment. Stratum corneum is a principal barrier and normally contains 10-20% water. Skin barrier function may be perturbed by physical, chemical, therapeutic and pathological factors; even changes in environmental humidity may also induce the pathophysiologic alterations. Increasing stratum corneum hydration can progressively reduce its barrier efficiency.
Occlusion is created by covering the skin with tape, gloves, impermeable dressings or transdermal devices. In addition, certain topical vehicles such as those containing fats and oils (petrolatum, paraffin, etc.) may be occlusive. Moisturizer/emollients may functionally be occlusive. Most studies demonstrated a duration of moisture of minutes to hours. Loden provided extensive documentation of this area. Passive TEWL can be completely blocked by occlusion. The consequence is to increase stratum corneum hydration, thereby swelling the corneocytes, and promoting the uptake of water into intercellular lipid domains.
Occlusion alters many factors that may influence percutaneous absorption:
- Altering the partitioning between the surface chemical and the skin due to the increasing presence of water content of stratum corneum from a normal range of 10-20% up to 50%;
- Swelling the corneocytes and possibly altering the intercellular lipid phase organization;
- Increasing the skin surface temperature from a normal range of 32ºC to 37ºC;
- Increasing blood flow;
- Preventing the accidental wiping or evaporation (volatile compound) of the applied compound, in essence maintaining a higher applied dose;
- Serving as a reservoir of the drug for penetration as result of hydration.
Initially, a drug enters the stratum corneum under occlusion conditions. After dressing removal and the stratum corneum dehydrates, the movement of drug slows and the stratum corneum becomes a reservoir. However, occlusion does not enhance penetration of all chemicals. Skin hydration increased penetration of lipid-soluble, nonpolar molecules but had less effect on polar molecules. The absorption of more lipophilic steroids was enhanced by occlusion in man but the most water-soluble were not. In addition, physicochemical properties (such as volatility, partition coefficient, and aqueous solubility), anatomic site, and vehicle may also influence the effect of occlusion on absorption.
Actually, the effects of occlusion are complex and may produce profound changes: occlusion can alter epidermal lipids, DNA synthesis, epidermal turnover, microbial flora, pH, epidermal morphology, sweat glands, Langerhans cells stresses, wound healing, etc.
This information is an excerpt from the book A Dermatological View: From Physiology to Therapy. To learn more about this topic or to purchase the entire book, visit www.alluredbooks.com.
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