Skin diffusion potential

Although electrode gels are needed for good skin contact, hydrating electrolytes produce another source of electric potential, known as a skin diffusion potential, in addition to the skin battery. This diffusion potential arises because skin membranes are semipermeable to ions. The magnitude of this skin potential varies as a function of the salt composition in the electrolyte. 

OECD has adopted an in vitro test for skin absorption potential (OECD TG 428, Skin Absorption In Vitro Method). According to this guideline, excised skin from human or animal sources can be used. The skin is positioned in a diffusion cell consisting of a donor chamber and a receptor chamber, between the two chambers. The test substance, which may be radio-labeled, is applied to the surface of the skin sample. The chemical remains on the skin for a specified time under specified conditions, before removal by an appropriate cleansing procedure. The fluid in the receptor chamber is sampled at time points throughout the experiment and analyzed for the test chemical and/or metabolites. 

The percutaneous absorption picture can be qualitatively clarified by considering Fig. 3, where the schematic skin cross section is placed side by side with a simple model for percutaneous absorption patterned after an electrical circuit. In the case of absorption across a membrane, the current or flux is in terms of matter or molecules rather than electrons, and the driving force is a concentration gradient (technically, a chemical potential gradient) rather than a voltage drop [38]. Each layer of a membrane acts as a diffusional resistor. The resistance of a layer is proportional to its thickness (h), inversely proportional to the diffusive mobility of a substance within it as reflected in a... 

Membrane diffusion illustrates the uses of Fick s first and second laws. We discussed steady diffusion across a film, a membrane with and without aqueous diffusion layers, and the skin. We also discussed the unsteady diffusion across a membrane with and without reaction. The solutions to these diffusion problems should be useful in practical situations encountered in pharmaceutical sciences, such as the development of membrane-based controlled-release dosage forms, selection of packaging materials, and experimental evaluation of absorption potential of new compounds. Diffusion in a cylinder and dissolution of a sphere show the solutions of the differential equations describing diffusion in cylindrical and spherical systems. Convection was discussed in the section on intrinsic dissolution. Thus, this chapter covered fundamental mass transfer equations and their applications in practical situations. 

Because of its pharmacokinetic features (pronounced bioaccessability upon oral use, diffusion to tissues and permeation into them, broad spectrum of antibacterial activity, and so on), fluoroquinolones have considerable potential for treating infections of practically any anatomic localization. Fluoroquinolones are very effective in treating infections of the respiratory tract, urinary tract, bones, skin, soft tissues, and so on. 

Topical local anesthesia is often used for eye, ear, nose, and throat procedures. Satisfactory topical local anesthesia requires an agent capable of rapid penetration across the skin or mucosa, and with limited tendency to diffuse away from the site of application. Cocaine, because of its excellent penetration and local vasoconstrictor effects, has been used extensively for ear, nose and throat (ENT) procedures. Cocaine is somewhat irritating and is therefore less popular for ophthalmic procedures. Recent concern about its potential cardiotoxicity when combined with epinephrine has led most otolaryngology surgeons to switch to a combination containing lidocaine and epinephrine. Other drugs used for topical anesthesia include lidocaine-bupivacaine combinations, tetracaine, pramoxine, dibucaine, benzocaine, and dyclonine. 

The major barrier of the skin is the outermost dead layer, the stratum corneum. A number of routes of penetration of a drug, across this region can be identified. First, the appendages, the pilosebaceous and eccrine glands, form a potential shunt route across the stratum corneum. The relative surface area of these is very small (<0.1%) and there has been little conclusive evidence to suggest that this is a major route. Second, the penetrant could diffuse across the entire stratum corneum through the dead cells, the corneocytes. A large surface area is available but the... 

To improve topical therapy, it is advantageous to use formulation additives (penetration enhancers) that will reversibly and safely modulate the barrier properties of the skin. Fick s first law of diffusion shows that two potential mechanisms are possible. The two constants that could be altered significantly are the diffusion coefficient in the stratum corneum and the concentration in the outer regions of the stratum corneum. Thus, one of mechanisms of action of an enhancer is for it to insert itself into the bilayer structures and disrupt the packing of the adjacent lipids, thereby, reducing the microviscosity. The diffusion coefficient of the permeant will increase This effect has been observed using ESR and fluorescence spectroscopy [16,17]. 

Care has to be taken when considering simple concentrations of the permeant since the driving force for diffusion is really the chemical potential gradient. As stated above the maximum flux should occur for a saturated solution of the permeant. However, if supersaturated solutions are applied to the skin, it is possible to obtain enhanced fluxes [27]. This can only be true if the outer skin lipids are capable of sustaining a supersaturated state of the diffusant. Figure 4.4 shows the linear increase in skin permeation with degree of supersaturation, and Fig. 4.5 demonstrates... 

The uptake component estimates the amount absorbed through the skin, the lungs or the gastrointestinal wall. This denotes the amount that reaches systemic circulation. If information on the fraction absorbed is available, this can be specified. Otherwise, simple diffusion models can be used to estimate the fraction taken up. As an alternative, uptake can be set to 100 %, in which case potential doses are calculated by the program. 

The application of an iontophoretic current to solute ions on the surface of the skin causes solute ions to traverse the skin along pathways that offer the least electrical resistance. These pathways may or may not be the same as those used during the passive diffusion of solutes through the skin, because the imposition of an exogenous transdeimal potential may cause changes in the skin s permeability and create new routes of permeation. Figure 2 shows three... 

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