Drug Permeation Across the Skin: Effect of Penetrant Hydrophilicity

Tojo, Kakuji; Chiang, Chin-Chih; Chien, Yie W.

doi:10.1002/jps.2600760208

Cited by 103 publications

(37 citation statements)

References 10 publications

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“…Due to a small area of the hole, we assume that the stratum corneum is peeled homogeneously over the opening of the hand piece. The skin treated by PEPITA was then excised to place in the in vitro side-by-side diffusion cell 7) for measuring the rate of penetration of a model drug, 17b-estradiol. We found previously that the model drug is negligibly bound in the skin.…”

Section: Methodsmentioning

confidence: 99%

Effect of Microdermabrasion on Barrier Capacity of Stratum Corneum

Fujimoto

Shirakami

Tojo

2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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Controlled microdermabrasion is a methodology which allows to slowly abrade the cutaneous surface, stratum corneum, up to the level desired in a non-traumatic way. The dermabrasion techniques of stratum corneum have been used for the treatment of stretch marks, wrinkles smoothing and acne scars.1) The controlled dermabrasion can also be applied to estimate the rate of drug penetration across the skin under in vivo conditions, 2,3) where the amount of the stratum corneum removed by each dermabrasion treatment must be precisely controlled. 2)A conventional method for peeling the stratum corneum is tape stripping; the human stratum corneum is reported to be completely removed by about 20 tape stripping. 4,5) The tape stripping is, however, time consuming and the amount of stratum corneum removed may vary in a complicated manner according to the pressure applied by subjects. For the in vivo evaluation of the rate of penetration, 2) therefore, the tape stripping technique requires quick and reproducible operation under controlled pressure on the adhesive tape. This is not practical to be carried out in a simple tape stripping operation.In order to overcome the difficulty associated with the tape stripping method, we have attempted to apply controlled microdermabrasion for removing the stratum corneum, quickly, simply and reproducibly. In the present microdermabrasion, the stratum corneum can be peeled partly or completely according to the number of treatment or the setting time of the probe of microdermabrasion on the skin surface. It is also possible to control precisely the amount of the stratum corneum removed by each treatment, and therefore we can avoid the damage of viable tissue due to over-treatment.In the present paper, we have investigated the relationship between the barrier capacity of the stratum corneum, which can be defined as the rate of drug penetration, and the operating conditions of microdermabrasion of the skin. The enhancement in the rate of penetration by skin treatment is measured as a function of the number of the treatment or the setting time of the probe for microdermabrasion. The rate of skin penetration following the treatment is also compared with those obtained in a conventional tape stripped skin. ExperimentalA microdermabrasion system, PEPITA (Fig. 1, Mattioli Engineering, Florence, Italy, Inter Face Co. Tokyo, Japan) was used for peeling the stratum corneum. It has been widely used in Europe and recently received FDA approval for use in the United States. PEPITA is a new device that allows the projection of a flow of inert corundum crystals on the skin through a controlled graduated vacuum.6) The fine corundum particles, being quickly in contact with the skin surface, abrade and remove the stratum corneum, either partly or completely, without damaging the deeper layer of the viable skin.Immediately after sacrificing the animal, a hand piece whose tip is pierced by a small elliptical hole (approximately 4.5ϫ9 mm) (Fig. 1) was placed on the surface of the dorsal skin of hairless mouse ...

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Section: Methodsmentioning

confidence: 99%

Effect of Microdermabrasion on Barrier Capacity of Stratum Corneum

Fujimoto

Shirakami

Tojo

2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…2) After the application of prednisolone-TTS (area, 2 cmϫ5 cmϭ10 cm 2 /patch; dose, about 3 mg/patch) to the shaved central abdominal skin of the rats, about 0.5 ml of blood was collected at 2, 4,6,8,12,18, and 24 h from the sampling port in the cannula and plasma was then obtained from the blood by centrifugation. During the experiment, the rats were free moving and allowed free access to food and water.…”

Section: In Vivo Application Of Prednisolone-tts In Rats and Tissue Smentioning

confidence: 99%

“…3,4) HPLC Assay of Prednisolone The prednisolone concentration in the in vivo experiment was determined under the following conditions. A semi-microcolumn HPLC system (Nanospace SI-1, Shiseido Co., Ltd.) was used as the HPLC system.…”

Section: In Vivo Application Of Prednisolone-tts In Rats and Tissue Smentioning

confidence: 99%

Drug Delivery to the Eye with a Transdermal Therapeutic System.

Isowaki

Ohtori

Matsuo

et al. 2003

Biological & Pharmaceutical Bulletin

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“…This suggests that flux increases in these compounds are driven by increased diffusivity. It is well recognised that diffusivity is independent of solute lipophilicity when the vehicle does not alter the properties of the stratum corneum (107,141). However, this may not be the case when the vehicle does affect the stratum corneum.…”

Section: Penetration and Solubility Datamentioning

confidence: 99%

“…Physicochemical properties including molecular size, melting point, lipophilicity, solubility and hydrogen bonding acceptor ability have been considered to be important in determining permeation flux (89,140). affecting the partitioning between the stratum corneum lipids and other stratum corneum components; (c) increasing its solubility in the stratum corneum lipids (141). Accordingly, skin absorption depends upon the physiochemical properties of the solutes (69), so that lipophilic compounds penetrate more easily than hydrophilic compounds and lower MW more easily than high MW (69).…”

Section: Introductionmentioning

confidence: 99%

Targeted skin delivery of topically applied drugs by optimised formulation design

Abd¹

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Early research concentrated on the relationship between a solute's physicochemical properties and its skin permeation, mostly from simple solutions. Relatively less is known about how vehicles, particularly complex ones, might also affect skin permeation by altering the properties of the skin, although this is an area that has attracted much interest. Key requirements for topical delivery is understanding the relationships between drug-vehicle, drug-skin or drug -vehicle -skin interaction. In this project, understanding this relationship was crucial to designing novel formulations able to deliver drugs with different lipophilicity topically or systemically. The first aim was to explore the impact of various solution compositions on skin permeation of some model drugs. I compared in vitro maximum penetration fluxes (Jmax) and solubilities of the vehicles (Sv) and of the stratum corneum (SSC) and derived diffusivities (D*) for four drugs (caffeine, minoxidil, lidocaine and naproxen) having a range of lipophilicities. I used a range of solvent vehicles that were hypothesised to affect the skin to differing degrees to evaluate vehicle effects on permeability parameters.If neither the vehicle nor the solute alters the properties of the skin, maximum (or saturated) solute flux is independent of both the vehicle composition and the solute's saturated solubility in that vehicle. These findings were confirmed in this study for all four drugs used.The permeation of caffeine, minoxidil, lidocaine and naproxen were found to be selectively enhanced by vehicles containing specific excipients that were hypothesised to alter the properties of the skin. The greatest effects were seen on flux and diffusivity by the eucalyptol (EU) and oleic acid (OA) vehicles on the more hydrophilic compounds, caffeine and minoxidil. We concluded that enhanced solute fluxes were mainly driven by increased diffusivity in the stratum corneum.I also examined the extent of skin permeation enhancement of the hydrophilic drug caffeine and lipophilic drug naproxen applied in nanoemulsions incorporating skin penetration enhancers. Infinite doses of fully characterised oil-in-water nanoemulsions containing the skin penetration enhancers oleic acid or eucalyptol as oil phases and caffeine (3%) or naproxen (2%) were applied to full-thickness skin and human epidermal membranes in Franz diffusion cells, along with aqueous control solutions. Caffeine and naproxen fluxes were determined over 8 h. Solute solubility in the formulations and in the stratum corneum, as well as the uptake of product components into the stratum corneum were measured.The nanoemulsions significantly enhanced the skin penetration of caffeine and naproxen compared to aqueous control solutions. The maximum flux enhancement of caffeine was III associated with a synergistic increase in both its solubility in the stratum corneum and skin diffusivity. Enhanced skin penetration in these systems is largely driven by uptake of formulation excipients containing the active compounds into th...

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Drug Permeation Across the Skin: Effect of Penetrant Hydrophilicity

Cited by 103 publications

References 10 publications

Effect of Microdermabrasion on Barrier Capacity of Stratum Corneum

Effect of Microdermabrasion on Barrier Capacity of Stratum Corneum

Drug Delivery to the Eye with a Transdermal Therapeutic System.

Targeted skin delivery of topically applied drugs by optimised formulation design

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