Transdermal permeation

PS Banerjee, WA Ritschel. (1989). Transdermal permeation of vasopressin. II. Influence of azone on in vitro and in vivo permeation. Int J Pharm 49 199-204. 

N. Bodor, T. Loftsson, W. M. Wu, Metabolism, Distribution, and Transdermal Permeation of a Soft Corticosteroid, Loteprednol Etabonate , Pharm. Res. 1992, 9, 1275-1278 N. Bodor, W. M. Wu, T. Murakami, S. Engel, Soft Drugs 19. Pharmacokinetics, Metabolism and Excretion of a Novel Soft Corticosteroid, Loteprednol Etabonate, in Rats , Pharm. Res. 1995, 72, 875-879. 

Monti D, Giannelli R, Chetoni P, Burgalassi S. Comparison of the effect of ultrasound and of chemical enhancers on transdermal permeation of caffeine and morphine through hairless mouse skin in vitro. Int J Pharm 2001 229 131-137. 

Azone (laurocapram) is used extensively as a transdermal permeation enhancer, and has also found use in buccal drug delivery. It is a lipophilic surfactant in nature (Figure 10.4). Permeation of salicylic acid was enhanced by the pre-application of an Azone emulsion in vivo in a keratinized hamster cheek pouch model [35]. Octreotide and some hydrophobic compounds absorption have also been improved by the use of Azone [36], Azone was shown to interact with the lipid domains and alter the molecular moment on the surface of the bilayers [37], In skin it has been proposed that Azone was able to form ion pairs with anionic drugs to promote their permeation [38],... 

When investigating the effects of water on transdermal permeation, animal skin may yield results markedly different to human data. For example, hairless mouse skin is unsuitable for modeling human stratum corneum regarding hydration effects the murine skin, when hydrated for 24 h, became grossly more permeable than human skin membranes [8]. Thus water effects on skin permeability obtained using animal models need cautious assessment. 

Vavrova, K., et al. 2003. L-serine and glycine based ceramide analogues as transdermal permeation enhancers Polar head size and hydrogen bonding. Bioorg Med Chem Lett 14 2351. 

Relatively little is known about the structure of stratum corneum, even though it is considered the primary barrier in transdermal permeation of most permeants. Traditional permeability studies of full-thickness skin (1-12) have implied molecules permeated through the skin by various polar or nonpolar pathways depending on the hydrophilicity or lipophilicity of the permeant. Coupling of macroscopic and molecular-level investigations of thermally induced alterations of the stratum corneum are beginning to provide insight into the molecular structure and barrier function of the stratum corneum. 

To deliver a therapeutically-effective dose transdermally using a TDD system with a reasonable size (e.g., < 20 cm ), the barrier properties of the skin for drug permeation must be overcome to effectively deliver the drugs transdermally at a controlled rate. The following approaches have been shown to potentially decrease the skin s barrier properties and enhance the transdermal permeation of the drugs (ji) ... 

Peira, E., Scolari, P, and Gasco, M. R. (2001),Transdermal permeation of apomorphine through hairless mouse skin from microemulsions, Int. J. Pharm., 226(1-2), 47-51. 

Visualization of Stratum Corneum and Transdermal Permeation Pathways... 

Shed snake skin has been proposed as a relatively good model for human skin in transdermal permeation studies [66]. Hirvonen et al. [67] compared the transdermal iontophoresis of sotalol and salicylate in shed snake skin, Elaphe obsoleta, and human cadaver skin. They advised that snake skin should be used with caution as a model for human skin because snake skin has anion-selective properties while human skin has cation-selective properties. 

Urea promotes transdermal permeation by facilitating hydration of the stratum corneum and the formation of hydrophilic channels. ... 

Wongpayapkul, L. Chow, D. Comparative evaluation of various enhancers on the transdermal permeation of propranolol hydrochloride. Pharm. Res. 1991, 8, S140. 

Turner, N.G. Nonato, L.B. Visualization of stratum corneum and transdermal permeation pathways. In Mechanisms of Transdermal Drug Delivery Potts, R.O., Guy, R.H., Eds. Marcel Dekker, Inc. New York, 1997 83,14-0. 

Over the last 20 years, transdermal route of delivery has been considered as a means for systemic drug administration. Over this period, sonophoresis has been attempted to enhance systemic transdermal delivery. Levy et al. ° showed that 3-5 min of ultrasound exposure (IMHz, 1.5W/cm ) increased transdermal permeation of mannitol and physostigmine across hairless rat skin in vivo by up to 15-fold. They also reported that the lag time typically associated with transdermal drug delivery was nearly-completely eliminated after exposure to ultrasound. ° ... 

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