8/15/2019 Transdermal Drug Absorption

1/1

Transdermal drug absorption

For selecterd drugs (e.g., potent drugs with therapeutic doses that are relativelysmall), transdermal drug delivery ofer many potential adventages over othertraditional routes o administration. Examples o drug classes ormulated as

transdermal products (e.g., drug contained in reservoir or hydrogel adhesive matrix,drug combined in hydroalcoholic gels) currently include hormones(estrogens,progestins, testosterone), topical anesthetics, analgesics, antihypertensive agents,and vasoactive substance (e.g., nitroglycerin).

For transdermal penetration o most molecules, the stratum corneum is consideredto be the rate limiting barrier. Translocation o a drug into the dermis re!uires that itbe able to permeate the stratum corneum. "s illustrated in #gure $ %&, permeationoccurs either via an intercellular route, through the intracellular lipid domains, or viathe transcellular route, which re!uires the drug to partition into and difuse throughthe 'eratin bric's and into and across intercellular lipid. *n the lipid composition o

the stratum corneum in mature (adult) s'in, the ma+or ractions represented areneutral lipid (approximately - ), sphingolipids (%- ), and a small amount o polarlipids and nonpolar material (e.g., s!ualene).

"n increasingly common approach or enhancing transdermal penetration o therapeutic drugs is to employ physicochemical approaches (e.g., use o hydroalcoholic gels, eutectic mixtures) or to deploy a drug delivery system utili/ingliposomes. 0iposomes are discrete vesicles composed o lipids, the most efectivebeing those ound in the stratum corneum. They can be ormed via nano aggregatepreparation by a variety o methods (e.g., dehydration1rehydration method) thatenable the active drug to be encapsulated therein. 2ur actans can also be added tospeci#c liposomal ormulations to produce ultrade ormable vesicles3 by increasingthe elasticity o the lipid bilayers,this improves transdermal drug delivery. Theprocess o translocation o a drug containing liposome through the stratum corneumis illustrated in #gure $ %4.

Figure $ %&. diagram o the bric' and mortar model o the stratum corneum, with aa simpli#ed lamellar organi/ation o intercellular domain showing the ma+or stratumcorneum lipids. "lso show are the possible drug permeation pathways throughintact stratum corneum5 the transcellular or the tortuous intercellular pathway ( romEl 6aghraby et al., with permission).

Figure $ %4. possible mechanisms o action o liposomes as s'in drug deliverysystems. (") is the ree drug mechanism, (7) is the penetration enhancing processo liposome components, (8) indicates vesicle adsorption to and1or usion with thestratum corneum(28), and (9) illustrates intact vesicle penetration into or (E)through the intact s'in (not to scale) ( rom El 6aghraby et al., with permission).