Mechanisms, skin permeation enhancement

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... 

Pershing, L.K., L.D. Lambert, and K. Knutson. 1990. Mechanism of ethanol-enhanced estradiol permeation across human skin in vivo. Pharm Res 7 170. 

Godin, B., and E. Touitou. 2004. Mechanism of bacitracin permeation enhancement through the skin and cellular membranes from an ethosomal carrier. J Control Release 94 365. 

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. 

A permeation enhancer can be defined as a compound that alters the skin barrier function so that a desired drug can permeate at a faster rate. Dozens of enhancers are patented each year, and several books have been written summarizing the work and proposing mechanisms of enhancement.70-72 The permeation enhancers may be classified simply as polar and nonpolar ones. They can be used individually or in combination, such as binary mixtures. For several drugs, the flux across skin was observed to be linear with that of the most widely used enhancer, ethanol.73-75 Another polar enhancer, isopropanol, facilitated ion association of charged molecules and enhanced the transport of both neutral and ionic species across the stratum corneum.76 77 While polar enhancers traverse the skin, nonpolar enhancers are largely retained in the stratum corneum both aspects make the combination a superior enhancer to the individual enhancers.78... 

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

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). 

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). 

Dermal and transdermal delivery requires efficient penetration of compounds through the skin barrier, the bilayer domains of intercellular lipid matrices, and keratin bundles in the stratum corneum (SC). Lipid vesicular systems are a recognized mode of enhanced delivery of drugs into and through the skin. However, it is noteworthy that not every lipid vesicular system has the adequate characteristics to enhance skin membrane permeation. Specially designed lipid vesicles in contrast to classic liposomal compositions could achieve this goal. This chapter describes the structure, main physicochemical characteristics, and mechanism of action of prominent vesicular carriers in this field and reviews reported data on their enhanced delivery performance. 

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