Epidermis, diffusion through

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. 

For a substance to be absorbed into the body following dermal exposure, it must initially dissolve in the stratum corneum sublayer, then diffuse through the remaining sublayers of the epidermis and into the dermis, where it will eventually diffuse into the blood capillaries. This absorption barrier ranges in thickness from 100 to 1000 pm, depending on area of the body (Klaassen and Rozman, 1991). 

In certain situations, the diffusion process occurs concurrently with a particular reaction in the membrane. For instance, when a prodrug (i.e., estradiol acetate) diffuses through the skin, an enzyme in the viable epidermis converts the prodrug to estradiol and acetate. A diester prodrug (i.e., PNU-82, 899) diffuses across a Caco-2 cell monolayer, which extensively metabolizes the diester to a monoester. 

The conductance gj and the resistance include all parts of the pathway from the site of water evaporation to the leaf epidermis. Water can evaporate at the air-water interfaces of mesophyll cells, at the inner side of epidermal cells (including guard cells), and even from cells of the vascular tissue in a leaf before diffusing in the tortuous pathways of the intercellular air spaces. The water generally has to cross a thin waxy layer on the cell walls of most cells within a leaf. After crossing the waxy layer, which can be up to 0.1 pm thick, the water vapor diffuses through the intercellular air spaces and then through the stomata (conductance = g, resistance = Fig. 8-5)... 

The intact epidermis behaves qualitatively as do cellular membranes in general (Scheuplein Blank, 1971). Topically applied chemical substances diffuse through the functional barrier provided by the epidermis at rates determined largely by their lipid/water partition coefficients but more slowly than through cellular barriers elsewhere in the body (Scheuplein, 1965). Percutaneous absorption in vivo is a summation of ten steps that have been enumerated by Wester Maibach (1983). 

The percutaneous absorption or the transdermal delivery of a drug occurs in the following manner. Initially a topically applied drug is absorbed into the stratum corneum and diffuses through that layer of skin into the epidermis and then into the dermis where drug... 

Where is the area of the patch Qp, the concentration of drug in the patch R, the overall resistance and R, the resistance to release from the patch. There are a number of situations one can consider, such as the patch resistance limits the delivery, diffusion through the epidermis limits delivery, or the concentration of the drag is kept constant in the patch by using solid hydrogels. When diffusion through the epidermis layer limits, the rate of drug delivery rate is... 

Most studies on percutaneous absorption emphasize the penetration of drugs, toxins, and other solutes into and through the skin as described in this book. Percutaneous absorption is also dependent on the clearance of solutes from the skin and transport into deeper layers of the skin (Figure 13.1). Clearance mechanisms in the avascular viable epidermis, diffusion in the dermis, and export from/within the dermis include solute diffusion and physiological transport by the dermal blood and lymphatic systems. This chapter focuses on the nature of these clearance mechanisms and how they affect the rates of percutaneous absorption and the levels of solute in skin and tissue. We consider first the role of blood flow, followed by the role of binding, transport to deeper tissues, and then the role of lymphatics. 

The diffusant molecule from a topically applied formulation has three potential routes of entry to the subepidermal tissue (1) the transappenda-geal route, (2) the transcellular route and (3) the intercellular route (Fig. 2) [ ] Percutaneous absorption refers to the overall process of mass transport of substances applied topically and includes their transport across each layer of the skin and finally their uptake by the microcirculation of the skin. The process of percutaneous absorption can be described by a series of individual transport events occurring in sequence. First, deposition of a penetrant molecule onto the stratum corneum, then the diffusion through it and through the viable epidermis, the passage through the upper part of the papillary dermis, and finally uptake into the microcirculation for subsequent systemic distribution [1,3,4]. The viable tissue layers and the capillaries are relatively permeable, and the peripheral circulation is sufficiently rapid,... 

Human skin is an efQcient barrier which protects the body against toxic chemicals. Stratum comeum (SC), the nonviable outermost of the five layers of the epidermis, is mostly responsible for barrier functions [147,148]. This layer differs in thickness in various anatomical sites. Therefore, a rate-limiting step for the penetration of most chemical substances is diffusion through the SC, and this may vary depending on its thickness [149,150]. 

Absorption through human skin can occur at a limited number of places at the openings in the skin surface for the sweat ducts, at the openings forthe hair follicles and sebaceous glands, and through the stratum comeiun, the outermost layer of the epidermis. Most skin absorption does, in fact, occur by passive diffusion through the epidermis. The permeability... 

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