Dermal preparations penetration

Physiological factors also determine the effectiveness of dermal preparations. The thickness of the skin varies across the body. The penetration rate is higher when applied on thin skin (e.g. behind the ear, on the eyelid or scrotum) than when applied on thick skin (e.g., palm of the hand, sole of the foot). Comparing the skin of babies and adults, the ratio between body surface (skin) and body volume is larger for babies. In addition, skin absorption in term and in preterm new-boms is increased because their stratum comeum is thinner and the epidermis of children is better perfused and hydrated compared to adults. As a result, the toxicity of active substances applied on a baby s skin can be much higher than on an adult s skin. 

Also linalool alone, one of the most prominent monoterpene alcohols, is used in many dermal preparations as penetration enhancer. In a series of in vitro studies it was shown that linalool enhanced its own penetration (Cal and Sznitowska, 2003) as well as the absorption of other therapeutics, such as haloperidol (Vaddi et al., 2002a, 2002b), metoperidol (Komuru et al., 1999), propa-nolol hydrochloride (Kunta et al, 1997), and transcutol (Ceschel et al., 2000). Cal (2005) showed in another in vitro stndy the influence of linalool on the absorption and elimination kinetics and was able to prove that this monoterpene alcohol furnished the highest absorption ratio compared to an oily solution or an 0/W emulsion. 

Because skin exhibits many of the properties of a lipid membrane, dermal penetration can often be enhanced by increasing a molecule s lipophilicity. Preparation of an ester of an alcohol is often used for this purpose since this stratagem simultaneously time covers a hydrophilic group and provides a hydrophobic moiety the ready cleavage of this function by the ubiquitous esterase enzymes assures availability of the parent drug molecule. Thus acylation of the primary alcohol in flucinolone (65) with propionyl chloride affords procinonide (66) the same transform... 

Percutaneous absorption is another route of interest for the administration of peptides [158], with metabolism being a complicating factor [159]. Thus, [Leu5]enkephalin and Tyr-Pro-Leu-Gly-NH2 were rapidly degraded on the dermal side after penetration through rat skin preparations [160]. The use of inhibitors confirmed the involvement of serine proteases and metalloenzymes. 

Polybrominated Diphenyl Ethers. No information was located regarding dermal absorption of PBDEs in humans. The only information regarding dermal absorption in animals is that from a study of absorption in an in vitro preparation (Hughes et al. 2001). In that study, " C-dccaBDE dissolved in tetrahydrofuran was applied to dorsal skin (three dose levels) excised from adult hairless female mice and fractions of receptor fluid were collected over a 24-hour period. Transfer of radioactivity to the receptor fluid was minimal, only 0.07 to 0.34% of the applied radioactivity. Two to 20% of the radioactivity was found in the skin, and the lowest dose applied had the highest percentage of the dose in the skin. Washing the skin with solvent 24 hours after application removed 77-92% of the applied dose. In this study, decaDBE did not easily penetrate the skin, but inferences to dermal absorption in humans based on these limited results may not be appropriate. 

Octyidodecanol has been used in the preparation of oil/ water microemulsions investigated as the vehicle for the dermal administration of drugs having no or low skin penetration. Octyidodecanol has also been evaluated as a solvent for naproxen when applied topically. ... 

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. 

After leaving the solution to rest for 24 hours and filtering it, UV exposure was what made it effective Solutions not exposed to UV did not appear to work. The skin was also prepared by UV exposure, and the solution was applied five times, leaving each coat to dry before the next application. Urkov then applied an occlusive mask. This mask allowed the superficial layers to hyperhydrate by blocking transepi-dermal water loss (TEWL). The hyperhydration dissolved the salicylic acid that would have precipitated on the skin without occlusion and could not have penetrated, as only the acids in solution can readily penetrate the skin barrier. He then applied zinc stearate powder (which is antiseptic and anti-inflammatory). The erythema subsided in 5-6 days and exfoliation was superficial. The solution can be kept in the fridge for 10 days. 

Lip Eyelid formula is a phenol peel that I first developed to increase dermatological safety and to achieve results without any occlusion on the sensitive skin of the eyelids. The same solution was then applied to the wrinkles around the mouth and then to the whole face, but with 24 hours occlusion in these two indications. It is an oil solution of phenol at over 60%. Four different oils are used in the various stages of the product s preparation. The aim of the oily formulation is to slow down the penetration of the phenol through the skin and to improve dermal and epidermal maceration. It limits the toxicity of phenol by saturating the biochemical hepatic detoxification pathways more slowly. 

Grissom, R.E., Monteiro-Riviere, N.A., and Guthrie, EE. (1987). A method for preparing mouse skin for assessing in vitro dermal penetration of xenobiotics, Tox. L tt., 36 251-258. 

Zhu S J, Yu D G and Zhu L-M. Preparation, sustained-release and trans-dermal penetration properties of drug-loaded hollow fibers. The 2nd IEEE International Conference on Bioinformatics and Biomedical Engineering (iCBBE2008), 18 May 2008, Shanghai, China. DOI 10.1109/ ICBBE.2008.674. 

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... 

The cosmetics and transdermal drug delivery fields are also expected to further benefit from the formulation of microemulsions from mild sugarbased surfactants. Lehmann et al. have studied the effect of such a microemulsion on dermal and corneal irritation, and hydrocortisone incorporation [105]. A microemulsion containing commercially available sucrose esters, isopropyl myristate, and propylene glycol and water was prepared as a water continuous system, and 16.5% hydrocortisone was loaded into the anhydrous base mixture. The formulation spread well on the skin due to the low surface tension of the system at 26 mN/m. While the microemulsion provided greater drug penetration, it also resulted in irritation and barrier compromise. The authors make the point that the formulation may be better suited to drugs that do not induce an irritation themselves. 

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