Mechanisms, skin permeation

Tokudome, Y., and K. Sugibayashi. 2004. Mechanism of the synergic effects of calcium chloride and electroporation on the in vitro enhanced skin permeation of drugs. J Control Release 95 (2) 267. 

Singh, P., Liu, P., and Dinh, S. Variation of human skin permeation in vitro Ionic vs. neutral compounds, in Bronaugh, R., and Maibach, H. (eds.), Percutaneous Absorption Drugs-Cosmetics-Mechanisms-Methodology, 3d ed. New York Marcel Dekker, 1999, pp. 633-657. 

A new generation of transdermal drug delivery (TDD) system was developed to contain one or more skin permeation enhancers in the surface adhesive coating layers. This TDD system has been found, experimentally, to release the enhancers to the surface of stratum corneum to modify the skin s barrier properties, prior to the controlled delivery of the active drug. The extent of enhancement in skin permeability appears to be dependent upon the chemical structure of drug to be delivered transdermally as well as the type and the concentration of enhancer used. The mechanism of skin permeation enhancement have been explored and are analyzed in this report. 

As the surface concentration of enhancer in the adhesive coating increased, the mechanism of skin permeation enhancement showed some changes as reflected in the relative contribution of fatty matrix and protein gel pathways (Table VII ). The behavior for azone and oleic acid at high concentration was observed to be identical to that at low concentration (compare the data in... 

Enhancers and other excipients may be used in these devices to promote skin permeation. The mechanisms by which enhancers exert their effects include ... 

The manner in which a test substance is applied to the skin surface can be a major determinant of its subsequent penetration and absorption. Several factors must be considered when selecting a suitable application procedure, including the nature of the vehicle, the permeant concentration, the amoimt of vehicle applied, the mechanism of application, the exposure time, and the method for removing an applied vehicle (if required). Many of these issues may be intrinsic to the purpose of the study. For example, risk assessment involving the study of the skin permeation of an ingredient in a cormnercially available product should be performed with the material in the formulation as it is marketed or used and with an application regime that mimics as closely as possible the in-use situation (see, for example. Brain et al., 1995 Walters, Brain, Howes, et al., 1997). 

Cutaneous preparatimis are inefficient formulations since only small amounts of the applied active substance penetrate the skin and reach the site of action. The first attempts to understand the mechanism of skin permeation and formulation effects of cutaneous preparations were described in 1960 [10]. Since then more research has been performed on rational design of dermal formulations. Much research is focused on improved skin penetration [11, 12]. Skin... 

Reservoir delivery systems have been developed in a variety of styles, ranging from microcapsules to hollow fibers to liposomes. Hayashi et al. (1994) produced delivery systems by encapsulating proteins and hormones inpoly-L-lactide microspheres by a solvent evaporation method. The release mechanism for hormones entrapped in liposomes was studied by Ho et al (1986). Progesterone and hydrocortisone skin permeation was enhanced by the presence ofthe liposomes no penetration ofthe liposomes was observed. Examples ofthe most common hydrogels employed in reservoir systems are crystalline-rubbery PEG, PAAm, celluloses, PAA, and PHEMA. 

F. Shakeel, S. Baboota, A. Ahuja, J. AU and S. Shafiq, Skin permeation mechanism and bioavailability enhancement of celecoxib from transdermaUy applied nanoemulsion. /. Nanotechnology, 6 8 doi 101186/1477-3155-6-8 (2008). 

Techniques to Investigate the Mechanisms of Skin Permeation of Terpenes... 

In addition, data obtained from infrared, thermal, and fluorescence spectroscopic studies of the outermost layer of skin, stratum corneum (SC), and its components imply enhancer-improved permeation of solutes through the SC is associated with alterations involving the hydrocarbon chains of the SC lipid components. Data obtained from electron microscopy and x-ray diffraction reveals that the disordering of the lamellar packing is also an important mechanism for increased permeation of drugs induced by penetration enhancers (for a recent review, see Ref. 206). 

The success of the Potts-Guy equation led many authors to advocate a single mechanism as the rate determining step for permeation through the skin barrier for all or at least a wide range of solutes diffusion was assumed to occur primarily via the interkeratinocyte lipids of the stratum corneum, a mixture of ceramides, fatty acids, and sterols. While from a macroscopic point of view these lipids may be modeled as a bulk solvent, on a microscopic scale they... 

Vibrational microspectroscopy provides a unique means for molecular level structure characterization of a variety of biological processes associated with skin. For the past several years, this laboratory has utilized Raman and IR spectroscopy, microscopy, and imaging to monitor the biophysics of the skin barrier, mechanisms of drug permeation and metabolism in intact tissue, and, more recently, the complex events that transpire during wound healing in an ex vivo skin model [1-6]. 

---