Transdermal

Transdermal is a route of administration wherein active ingredients are delivered across the skin for systemic distribution. Examples include transdermal patches used for medicine delivery, and transdermal implants used for medical or aesthetic purposes.

Although the skin is a large and logical target for drug delivery, its basic functions limit its utility for this purpose. The skin functions mainly to protect the body from external insults (e.g. harmful substances and microorganisms) and to contain all body fluids. It must be tough, yet flexible enough to allow for movement. The lipids in our skin serve as poor conductors of electricity and can hence protect us from electrical currents if the need so arises.

There are two important layers to the human skin: (1) the Epidermis and (2) the Dermis. For transdermal delivery, drugs must pass through the two sublayers of the epidermis to reach the microcirculation of the dermis.

The Stratum corneum is the top layer of the skin and varies in thickness from approximately ten to several hundred micrometres, depending on the region of the body. It is composed of layers of dead, flattened keratinocytes surrounded by a lipid matrix, which together act as a brick-and-mortar system that is difficult to penetrate.

The stratum corneum provides the most significant barrier to diffusion. In fact, the stratum corneum is the barrier to approximately 90% of transdermal drug applications. However, nearly all molecules penetrate it to some minimal degree. Below the stratum corneum lies the viable epidermis. This layer is about ten times as thick as the stratum corneum; however, diffusion is much faster here due to the greater degree of hydration in the living cells of the viable epidermis. Below the epidermis lies the dermis, which is approximately one millimeter thick, 100 times the thickness of the stratum corneum. The dermis contains small vessels that distribute drugs into the systemic circulation and to regulate temperature, a system known as the skin's microcirculation.

There are two main pathways by which drugs can cross the skin and reach the systemic circulation. The more direct route is known as the transcellular pathway. By this route, drugs cross the skin by directly passing through both the phospholipids membranes and the cytoplasm of the dead keratinocytes that constitute the stratum corneum.

Although this is the path of shortest distance, the drugs encounter significant resistance to permeation. This is because the drugs must cross the lipophilic membrane of each cell, then the hydrophilic cellular contents containing keratin, and then the phospholipid bilayer of the cell one more time. This series of steps is repeated numerous times to traverse the full thickness of the stratum corneum.

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Wikipedia