Transdermal absorption skin barrier

Schaefer, H. and Redelmeier, T.E. (eds) (1996) Skin barrier. Principles of percutaneous absorption. Karger AG, Basel. Cleary, G.W. (1993) Transdermal Delivery Systems A Medical Rationale. In Topical Drug Bioavailability, Bioequivalence, and Penetration. (Shah, V.P. and Maibach, H.I., eds). Plenum Press, New York, pp. 17-68. 

One of the available method to improve the transdermal absorption of drugs is to reduce this barrier function of skin by the aid of enhancers. 

This is the primary barrier to drag absorption across the skin. Transdermal bioavailability therefore and strategies to improve delivery often involve changing the composition or the organization of the intercellular lipids. Such enhancing technologies are of course feasible, but not without problems (see below). 

These testosterone systems illustrate two different approaches to solve the problem of inadequate percutaneous absorption rate. In the former case, the patch must be applied to the body s most permeable skin site, the scrotum (which has been shown to be at least five times more permeable than ary other site). In the latter, the difficulty is resolved by creating a transdermal formulation which includes excipients to reduce barrier function. Neither solution is ideal scrotal application is clearly not preferred from a patient compliance standpoint on the other hand, permeation enhancers, by their very nature, tend to be irritating (and the more effective they are, the greater the irritation they provoke). This general problem, which presently limits the application of transdermal delivery, is now discussed in more detail. 

The transdermal route suffers from the inability of the skin to deliver large doses, the relatively slow plasma increase when compared with other routes, and the potential for irritation. However, several products utilizing this route of administration are currently on the market. Absorption can be enhanced with molecules that maintain an appropriate hydrophilic-lipophilic balance for efficient passage through the barrier of the stratum corneum. ... 

The use of ultrasound (US) to enhance percutaneous absorption (so-called sonophoresis or phonophoresis) has been studied over many years, and is the basis of US propagation and US effects on tissue, and the use of US in transdermal delivery have been reviewed in detail. The proposed mechanisms by which US enhances skin penetration include cavitation, thermal effects and mechanical perturbation of the SC that is, US acts on the barrier function of the membrane. ... 

Transdermal administration The development of the stratum comeum is complete at birth but is more perfused and hydrated than in adults. It is considered to have permeability similar to that of adults, except in preterm infants (80). Preterm neonates and infants have an underdeveloped epidermal barrier and are subject to excessive absorption of potentially toxic ingredients from topically applied products. Once matured (3-5 months after birth), infant skin presents less variability, but the ratio of surface area to weight is higher in children, when compared with that of adults. 

Medicinal products can be applied on the skin to treat local skin diseases (topical application) or to systemically administer an active substance (transdermal application). In the first case, the active substance should accumulate in or even on the skin and display its effect there. When transdermal administration is intended, the active substance should be transported through the skin followed by absorption into the systemic circulation. In the skin the stratum comeum (the most outer layer of 5-50 layers of dead cells, a homed layer of comeocytes, see Fig. 12.1 and Sect. 12.3.1) forms the major barrier for absorption of active substances. The layer is highly lipophilic in nature and is fully impermeable for hydrophilic active substances. Lipophilic active substances, when adequately formulated, may be absorbed via the skin. Typical characteristics which make an active substance suitable for transdermal transport are an octanol-water partition coefficient (expressed as log Pq/w) between 1 and 3 and a molecular mass below 500 Da [10, 11]. Moreover the dose should not exceed 20 mg per day. Hydrophilic active... 

To reach the systemic blood circulatory system, dmg from a transdermal patch must cross several layers of skin, as shown in Fig. 10. The top surface layer of skin, called the stratum comeum, represents the main barrier to dmg permeation. The stratum corneum is only 10-15 /rm thick, but it consists of layers of flattened, cornified cells that are quite impermeable. The interspace between these cells is filled with lipids, giving the stmcture a bricks-and-mortar form, with the cells being the bricks and the lipids being the mortar. The most important pathway for dmg absorption is through the lipid (mortar), which dictates... 

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