Skin, diffusion through

Fig. 4. Schematic of transdermal therapeutic system in operation. The dmg diffuses through the intact skin into capillaries and is then carried into the...

The demonstration of this behavioural response to a male pheromone signal is significant because of the manner in which the pheromone was delivered. Most other vertebrate examples of reproductive pheromones involve reception via the olfactory system(s). In contrast, D. ocoee females received the pheromone via diffusion through the dorsal skin. We assume that the well developed superficial capillary system of these lungless salamanders is the route by which the male pheromone was transported to whatever target tissue(s) initiated responses that affected female reproductive behaviour. 

The chemical incorporated in a vehicle should reach the surface of the skin at a suitable rate and concentration. If the site of action lies in the deeper layers of the epidermis or below, the substance must cross the stratum comeum, if the skin is intact. Both processes, diffusion from the dosage form and diffusion through the skin barriers, are inextricably linked. They should be considered simultaneously and can be influenced by the choice of formulation. 

This chapter starts with a short introduction on the skin barrier s properties and the methods employed for analyzing experimental data. This is followed by an overview of several selected approaches to predict steady-state diffusion through the skin. Then a few approaches that approximate the structural complexity of the skin by predicting drug diffusion in biphasic or even multiphasic two-dimensional models will be presented. Finally, the chapter concludes with a short summary of the many variables possibly influencing drug permeation and penetration. 

Phase separation controlled by diffusion exchange often results in a skin which is composed of a micellar assembly of nodules, as will be discussed below. When extremely hydrophobic polymers (e.g., modifled-PPO) are cast from dioxane into water (pg = p = p ) a dense polymer layer is formed at the solution s interface that somewhat resembles the type of layer formed by Interfacial polymerization. There is almost no inward contraction of the interfacial skin, and the coagulation process is controlled by diffusion through the dense, interfacial thin film. These result in an anisotropic membrane with a very fine "coral" structure (Figures 9 and 10). 

Local anaesthetics are readily absorbed through mucous membranes and damaged skin. These are weak bases and at tissue pH diffuse through the connective tissue and cellular membranes to reach the nerve fibres where ionization can occur. Amide type local anaesthetics (lignocaine, bupivacaine) are metabolised in the liver and in some cases the kidneys. These are considerably protein bound. For certain procedures the duration of action is prolonged by adding... 

After polymer skin formation, gel bubbles form on the device surface because the skin layer prevents any further outflow of water and pressure to expel water is exerted on the surface from the inside after shrinking [5], It is proposed that pressure is induced within the gel in the process of shrinking. This pressure may induce the outward convection of water. In the on state, drug is released from the surface by diffusion through the hydrated gel matrix. However, in the process from the on state to the off state upon increasing temperature, the drug must be released not only by diffusion but also by convective transport [9]. 

Molecular size greatly affects transport across cellular membranes. As molecular size increases, transport across membranes decreases, because increases in molecular size will increase "frictional resistance" and decrease the diffusivity through the cell membrane. Since molecular size is generally directly proportional to molecular mass, and molecular mass is easily calculated molecular mass is often used as a descriptor of molecular size. Hence, as a general rule, the lower the molecular mass, the smaller are the molecules composing the substance, and the more easily the substance can cross membranes and be absorbed from the gastrointestinal tract, lung, and skin. 

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