Frontiers in Drug Design and Discovery

Volume: 4

Across Skin Barrier: Known Methods, New Performances

Author(s): Krzysztof Cal

Pp: 162-188 (27)

DOI: 10.2174/978160805202810904010162

* (Excluding Mailing and Handling)

Abstract

Skin is still the desirable route for the delivery of drug substances into the human body. Transdermal drug delivery offers many advantages over the conventional oral route of application, such as the elimination of hepatic first-pass effect, reduced side effects, constant concentration of a drug in the blood. Human intact skin is normally permeable for molecules with log P in the range of 1-3, smaller than 500 Da and present in a unionized form. Usually, obtained fluxes of drug substances are too low for the induction of systemic therapeutic effects. It is caused by the specific structure and composition of the outer layer of the skin - the stratum corneum. Closely packed, built as “brick” (corneocytes) and “mortar” (lipid bilayers), the stratum corneum is the most important limiter for transdermal drug delivery. Molecules that permeated the stratum corneum are easily taken up by capillary vessels present in the deeper skin layers. This chapter presents different methods used for skin permeation enhancement. Various drug forms and carriers, chemical permeation enhancers, electrically supported methods and devices, and the stratum corneum bypassing or removing methods are described, and the recent achievements in the field and possible practical use in market products are discussed. The special subchapters are dedicated to the skin disposition of one of the most often used penetration enhancers - terpenes, and the use of cyclodextrins in formulations applied onto the skin.

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