Cutaneous administration can be desirable for both dermal and transdermal delivery. In case of dermal delivery, it is used to induce local effects (e.g. topically applied steroids or antibiotics). Transdermal delivery indicates that the target is beyond the skin and systemic concentrations are necessary. Drugs such as scopolamine, fentanyl, estrogen and nicotine are sometimes administered via such patches. In contrast to the oral route, drugs administered using skin-patches can provide nearly continuous dose administration via a rate-controlling membrane. Therefore, instead of a 'Dose', often the word 'Flux is used', which describes the (constant) rate of the drugs that move through the skin. This constant rate, the steady state flux (J_ss) leads to a more or less constant concentration in the systemic circulation (until the patch is depleted), which shares many similarities with intravenous infusion. Drugs will penetrate the skin via the transcellular, intercellular, or transappendageal (hair shafts and sweat glands) route, depending on the physicochemical properties of the drug (e.g. size, lipophilicity). The absorption is usually slower compared to oral formulations, and there is a lag time before drug crosses the skin barrier and reaches the systemic circulation.

Most drugs have poor lipid solubility and thus are poorly absorbed through the skin. Particularly the outermost layer of the skin, the stratum corneum (horny layer), is a major barrier to overcome and consists of corneocytes (dead, terminally differentiazed cells) embedded in a lipid matrix (stacked, densely pack lipid layers). Although this stratum corneum barrier may hamper absorption through the skin, systemic effects can occur depending on the vascularisation of the tissue site. Besides, the first-pass metabolism will be evaded, although this does not mean that the bioavailability of transdermal delivery is 100%:

Drugs will only reach the systemic circulation if they can overcome the barrier, and when the drugs will actually be 'forced' to move from the patch into the skin. The driving force behind this movement - the steady state flux (J_ss) -  is passive diffusion, and factors that can improve the diffusion rate across the skin will lead to higher systemic (therapeutic) concentrations. These factors are:

1. the diffusion coefficient (D): a constant that depends on the characteristic of the drug and the stratum corneum. A higher diffusion coefficient indicates a higher diffusion rate. This can be achieved if the drug is easier to penetrate the stratum corneum, or if the stratum corneum is more permeable. Therefore, penetration enhancers (e.g. fatty acids) are added to topical formulations to reduce the 'viscocity' of the lipids in the stratum corneum, and thereby improve the permeability.
2. Drug concentration (C) in the patch: a higher concentration will lead to a higher concntration gradient from the patch to the skin.
3. Path length that the drug has to overcome to cross the stratum corneum (L): A thinner skin - particularly thicker stratum corneum - will increase the flux across the skin.
4. The partition coefficient (K): this represents how much of drug is dissolved in the mixture in the patch, and how much is dissolved in the stratum corneum. When the patch is applied, all drug is in the patch and none in the stratum corneum. So drug will partition from the patch into the stratum corneum. When more and more drug molecules are in the skin, there is a lower concentration gradient, and less drugs will partition from the patch into the skin. So a maximum or equilibrium will be achieved.

These 4 factors that lead to a steady state flux can all be put in one equation, better known as Fick's Law:

J_ss = -D · K · C / L

Note: The negative sign indicates that J is positive when movement is down the gradient. It is a mathematical correction and therefore only of 'arithmetic' value.

Thus, to obtain appropriate therapeutic concentrations, both the drug formulation or additives that change the permeability of the skin can positively affect the flux (and thus the total 'dose' deliverd over time). The easiest way to control this flux, is to have different patches with different concentrations or different sizes.