Skin, dermal drug-delivery

Prausnitz, M.R., et al. 1993. Electroporation of mammalian skin A mechanism to enhance trans-dermal drug delivery. Proc Natl Acad Sci USA 90 10504. 

Trawi-dermal drug delivery has become one of the fastest growing systems for some disease treatments. It has been demonstrated that the skin can be used as a... 

Most drugs do not penetrate epithelial barriers at rates sufficient for clinical usefulness without permeability enhancers, chemicals that are routinely added to dermal drug delivery products. 18 For example, using human skin in an in vitro study, it was demonstrated that sodium dichlofenac (K = 0.70) permeability was enhanced by a mixture containing the lipophiles oleic acid (K = 7.64) and c/-limonene (K = 4.57)J191... 

Keywords Dermal Drug delivery Permeability Skin Transdermal... 

Typical delivery systems can be utilised to achieve transdermal drug delivery or dermal drug delivery. The former involves the delivery of drugs through the skin... 

Applied to the skin in a transdermal patch (tra ns dermal therapeutic delivery systemX this drug is used to prevent or reduce the occurrence of nausea and vomiting that are associated with motion sickness. 

Chloroform can also permeate the stratum comeum of rabbit skin (Torkelson et al. 1976) and mouse skin (Tsuruta 1975). Percutaneous absorption of chloroform across mouse skin was calculated to be approximately 38 pg/min/cm, indicating that the dermal absorption of chloroform occurs fairly rapidly in mice. No reliable studies report the percutaneous absorption of chloroform in humans however, a few clinical reports indicate that chloroform is used as a vehicle for drug delivery (King 1993). Islam et al. (1995) investigated the fate of topically applied chloroform in male hairless rats. For exposures under 4 minutes, chloroform-laden water was applied to shaved back skin for exposures of 4-30 minutes, rats were submerged in baths containing chloroform-laden water. Selected skin areas were tape-stripped a various number of times after various delay periods. It appeared that there was an incremental build-up of ehloroform in the skin over the first four minutes. When compared to uptake measured by bath concentration differences, approximately 88% of lost chloroform was not accounted for in the stratum comeum and was assumed to be systemically absorbed. 

These linear kinetic models and diffusion models of skin absorption kinetics have a number of features in common they are subject to similar constraints and have a similar theoretical basis. The kinetic models, however, are more versatile and are potentially powerful predictive tools used to simulate various aspects of percutaneous absorption. Techniques for simulating multiple-dose behavior evaporation, cutaneous metabolism, microbial degradation, and other surface-loss processes dermal risk assessment transdermal drug delivery and vehicle effects have all been described. Recently, more sophisticated approaches involving physiologically relevant perfusion-limited models for simulating skin absorption pharmacokinetics have been described. These advanced models provide the conceptual framework from which experiments may be designed to simultaneously assess the role of the cutaneous vasculature and cutaneous metabolism in percutaneous absorption. 

While the infinite dose technique has been invaluable in the determination of important skin permeability parameters such as dermal penetration coefficients and in the development of transdermal drug delivery concepts, to mimic in vivo conditions, the so-called finite dose technique was developed. This is essentially a modification of the traditional steady-state method. The important difference is that the skin preparation is supported over the receptor so that the epidermal surface is exposed in a manner that mimics the real-life exposure scenario, and the compound of interest is applied to the surface of the skin in a manner also similar to exposure in vivo. Although the results of such studies may give valuable information about the absorption of materials under specific exposure conditions, they are generally not amenable to extrapolation to other exposures since no invariant skin properties such as penetration coefficients can be readily calculated. 

Because of the very extensive barrier properties of the stratum corneum, it is often necessary to increase the intrinsic rate of dermal or transdermal drug delivery to achieve the required therapeutic drug levels. In these instances, skin penetration and permeation enhancement... 

There is a paucity of published data on in vitro studies of dermal penetration in food animals. In one study comparing the effects of freezing on human and cow skin (27), it is alluded to that the follicular route of penetration predominates in the cow. These authors have also written an excellent review on topical drug delivery to cattle and sheep which should be consulted for further details (2S). In this work, studies on the dermal application of twenty four different substances are reviewed. Some interesting data on differential effects of dermal enhancers in different species underlines the problems inherent to interspecies extrapolations. One conclusion of this study was that "the barrier properties of sheep and cattle skin are not well understood." This situation has not improved in the intervening years. 

Merk, H.F. Jugert, F.K. Metabolic activation and detoxification of drugs and xenobiotica by the skin. In Dermal and Transdermal Drug Delivery—New Insigts and Perspectives Gurny, R., Teubner, A., Eds. Wiss.Verl. Ges. Stuttgart, 1993 91-100. 

ME provides another promising alternative for dermal and transdermal delivery of both hydrophilic and lipophilic drugs [117,118]. The use of MEs in skin drug delivery has been reviewed and it was noted that although many reports of cntaneous drug delivery potential of topical MEs have been published recently, most of the studies have not been very systematic or consecutive which hampered... 

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