• Journal of Pharmaceutical Investigation
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• v.25 no.3
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• pp.43-51
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• 1995

The in vitro skin permeability of 16 drugs with a wide span of lipophilicity (log P ranging from -0,95 to 4.40) was evaluated with an ethanol/panasate 800 (tricaprylin, P-800) (40/60) lipophilic binary vehicle and an ethanol/water (60/40) hydrophilic binary vehicle with lauric acid, The skin permeability of the drugs was enhanced by the use of the ethanol/P-800 (40/60) binary vehicle or the ethanol/water (60/40) binary vehicle with lauric acid; permeation rate was increased and lag time' was decreased. The relationship between lipophilicity and skin permeation rate of the drugs showed parabolic shapes with their peaks at much greater hydrophilic range compared with other past references. In the in vivo skin absorption of theophylline using abdominal rat skin, the ethanol/P-800 (40/60)-7% (w/w) ethycellulose gel produced a good feature as a sustained-release preparation, and the ethanol/water (60/40)-3 % (w/w) HPMC gel with lauric acid showed the highest BA value. The results suggest that the lipophilicity of a drug is a main factor for prediction of the skin permeability of the drug and that the ethanol/P-800 (40/60) binary vehicle and ethanol/water (60/40) binary vehicle with lauric acid would be good candidates for clinical transdermal application of hydrophilic drugs.

• Journal of Pharmaceutical Investigation
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• v.33 no.3
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• pp.163-169
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• 2003

In order to develop a film-forming transdermal drug delivery system, polyurethane (PU) based on poly(ethylene glycol) and poly(tetramethylene oxide) was synthesized and characterized. The synthesized PU was blended with Gantrez ES 225 (GT) to improve the adhesion property of film-forming agent to the skin. When film-forming gel formulation containing 3% ketoprofen (KP) was applied, transparent thin film was obtained within 5 minutes and adhered to the skin for 8 hours. In vitro percutaneous absortion studies were performed to determine the rate of ketoprofen absorption through guinea pig skin. A prominent effect of limonene on the skin permeability of ketoprofen was observed among the various skin permeation enhancers investigated. Considering mechanica properties of film and skin permeability of ketoprofen, 2% of limonene was optimal content in the film forming transdermal formulation.

• Journal of Pharmaceutical Investigation
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• v.33 no.2
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• pp.129-133
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• 2003

In order to evaluate the effects of vehicles and penetration enhancers on skin permeation of apomorphine, the skin permeation rates of apomorphine from vehicles of different composition were determined using Franz diffusion cells fitted with excised rat skins. Solubility of apomorphine in various solvents was investigated to select a vehicle suitable for the percutaneous absorption of apomorphine. The solvents used were propylene glycol (PG), $Transcutol^{\circledR},\;Labrasol^{\circledR},\;Labrafac hydro WL^{\circledR},\;Labrafil WL 2609 BS^{\circledR}$ and isopropyl alcohol. Even though permeation rates of apomorphine from each vehicle were low $(0.008-0.36\;{\mu}g/cm^2/hr)$, the combination of PG and $Labrafac^{\circledR}$ increased it significantly. The permeation rates of apomorphine from $PG/Labrafac^{\circledR}$ mixtures increased as the volume fraction of PG in the mixture increased. The maximum permeation rate of $18\;{\mu}g/cm^2/hr$ was achieved at 30% of PG, which decreased with further increase of PG fraction. A series of fatty acids, alcohols and monoterpenes were employed as penetration enhancers. Incorporation of each enhancer in the $PG/Labrafac^{\circledR}$ (30:70) mixture at the level of 10% improved the skin permeation significantly. The highest permeation rate, $117\;{\mu}g/cm^2/hr$, was attained with myristic acid.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.234.1-234.1
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• 2003

The effects of vehicles and penetration enhancers on the in vitro permeation of ketorolac tromethamine (KT) across excised hairless mouse skins were investigated. Among pure vehicles examined, propylene glycol monolaurate (PGML) showed the highest permeation flux, which was 94.3${\pm}$17.3 mg/cm$^2$/hr. Even though propylene glycol monocaprylate (PGMC) alone did not show high permeation rate, the skin permeability of DT was markedly increased by the addition of diethylene glycol monoethyl ether (DGME); the enhancement factors were 19.0 and 17.1 at 20 and 40% of DGME, respectively. (omitted)

• Archives of Pharmacal Research
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• v.27 no.3
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• pp.351-356
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• 2004

A transdermal preparation containing diclofenac diethylammonium (DDA) was developed using an O/W microemulsion system. Of the oils tested, lauryl alcohol was chosen as the oil phase of the microemulsion, as it showed a good solubilizing capacity and excellent skin permeation rate of the drug. Pseudoternary phase diagrams were constructed to obtain the concentration range of oil, surfactant and cosurfactant for microemulsion formation, and the effect of these additives on skin permeation of DDA was evaluated with excised rat skins. The optimum formulation of the microemulsion consisted of 1.16% of DDA, 5% of lauryl alcohol, 60% of water in combination with the 34.54% of Labrasol (surfactant)/ethanol (cosurfactant) (1:2). The efficiency of formulation in the percutaneous absorption of DDA was dependent upon the contents of water and lauryl alcohol as well as Labrasol: ethanol mixing ratio. It was concluded that the percutaneous absorption of DDA from microemulsions was enhanced with increasing the lauryl alcohol and water contents, and with decreasing the Labrasol:ethanol mixing ratio in the formulation.

• Journal of Pharmaceutical Investigation
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• v.31 no.3
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• pp.181-184
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• 2001

The purpose of this study was to develop transdermal drug delivery system (TDDS) for the combination of physostigmine and procyclidine. The effects of various pressure sensitive adhesives (PSA) on the percutaneous absorption of procyclidine across hairless mouse skin were evaluated to select an appropriate PSA. In addition, the influences of various vehicles on the percutaneous absorption of procyclidine from PSA matrix across hairless mouse skin were evaluated using flow-through diffusion cell system at $37^{\circ}C$. Physostigmine did not have any influence on the permeation rate of procyclidine. The flux of procyclidine was the highest in silicone and PIB and was relatively lower in SIS, Acryl, and SBS adhesive matrices, however, their use was limited by the crystallization of the drug in the matrix. Among acrylic adhesives, the permeability of procyclidine was the highest from poly (ethylene oxide) grafted acrylic adhesive. Some enhancers show different enhancing effect depending on the drug, however, many of the tested enhancers showed enhancing effect for the permeation of both procyclidine and physostigmine to some extent. $Crovol^{\circledR}$ EP 40 showed the highest enhancing effect on the permeation of both compounds. The size of TDDS to provide required permeation rate was estimated to be $35\;cm^2$ based on available information.

• Archives of Pharmacal Research
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• v.24 no.6
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• pp.578-583
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• 2001

To investigate the feasibility of developing a new tenoxicam plaster, the effects of vehicles and penetration enhancers on the in vitro permeation of tenoxicam from a pressure-sensititre adhesive (PSA) matrices across the dorsal hairless mouse skin were studied. Vehicles employed in this study were propylene glycol (PC)-oleyl alcohol (OAI), PG-oleic acid (OA), and diethylene glycol monoethyl ether (DCMI)-propylene glycol monolaurate (PCML) cosolvents with/without fatty acids. In this studys amines such as triethanolamine (TEA) and tromethamine (TM) were additionally used as a solubilized. Among PSAs used, $Duro-Tak^{\circledR}$87-2510 showed much higher release rate than either $Duro-Tak^{\circledR}$ 87-2100 or $Duro-Tak^{\circledR}$87-2196. The relatively high flux rate was obtained with the formulation of DCMI-PCML (40:60, v/v) with 3% OA and 5% TM, and the flux increased as a function of the dose;the initial flux up to 12 h was $4.98{\pm}1.38{\;}{\mu\textrm{g}}/{\textrm{cm}^2}/h$ at the tenoxicam dose of $50{\;} mg/70{\;}{\textrm{cm}^2}$. This flux was much higher than that of a commercial piroxicam patch ($Trast^{\circledR}$) ($1.24{\pm}0.73{\;}{\mu\textrm{g}}/$\textrm{cm}^2/hr$) with almost only one-third that of the commercial patch. Therefore, these observations indicated that these composition of tenoxicam plaster may be practically applicable.

• Journal of Environmental Health Sciences
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• v.43 no.1
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• pp.77-86
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• 2017

Objectives: The purpose of this study was to compare permeation characteristics in three skin types using oil-soluble benzoic acid and water-soluble caffeine after method condition optimization based on OECD guideline 428. Methods: A Franz diffusion cell, a reliable alternative method for skin permeation, was used. One-milliliter samples were taken and immediately replaced with fresh solution in the receptor chamber at regular time intervals (1, 2, 4, 7, 10 and 24 hr). The amount of test substances was measured by LC-MS/MS. Results: The permeation rate increased dose-dependently, and the permeation orders were $KeraSkin^{TM}$ > hairless mouse full skin > human cadaver epidermis for skin types, and benzoic acid solution > caffeine solution > benzoic acid cream > caffeine cream for type of test materials. Conclusion: According to the definitions of Marzulli, benzoic acid and caffeine would be classified as 'fast' and 'moderate' compared with the permeation of other chemical species. The setting conditions and permeation characteristics performed in this study are expected to contribute to future permeation studies.

• YAKHAK HOEJI
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• v.44 no.6
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• pp.595-600
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• 2000

Transdermal delivery of ketorolac tromethamine, a potent non-narcotic analgesic, through human cadaver skin was investigated in vitro. A mixture of ethanol/water (40/60) containing 0, 1, 3, 5, and 8 (w/v)% L-menthol were used as a vehicle and penetration enhancer respectively. The permeation of ketorolac through human cadaver skin from saturated drug solution was evaluated at $37^{\circ}C$ with modified Franz diffusion cell. The in vitro skin flux and lag time were $1.23\;{\pm}\;0.11\;{\mu}g/cm^2{\cdot}hr$ and $5.56\;{\pm}\;0.34\;hr$, respectively. The cumulative amount of penetrated ketorolac containing L-menthol in ethanol/water (40/60) binary system was increased by the following order; 3%, 5%, 8%, 1%, 0%, and the lag time was decresed by the following order; 3%, 5%, 8%, 0%, 1%. The results suggested that a potential use of 3% L-methol is an effective penetration enhancer of ketorolac tromethamine through the human cadaver skin.

• Journal of The Korean Society of Clinical Toxicology
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• v.3 no.2
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• pp.122-125
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• 2005

Paraquat, is a widely used for its great effect as a herbicide. But the mortality rate by paraquat intoxication is known to be very high. It is thought to act by changing form to superoxide and peroxide free radical. Almost paraquat intoxication is through ingestion. A few intoxication of paraquat is through skin absorption. But there was no known death case through skin absorption. We experienced a case of a expired patient by paraquat intoxication through skin abrasion and scratching wound. A 75-year-old man was visited emergency room after motorcycle accident during transporting paraquat. He has multiple abrasion and scratching wound on extremities, and pelvic bone fracture. There was no evidence of ingestion of paraquat. But serum/urine gramoxone level was all positive. In spite of wound irrigation and hemoperfusion, his condition was been gone form bed to worse. 2 days after, multiple organ failure and the respiratory arrest were developed and he was expired. Paraquat intoxication through skin wound is extremely dangerous and death by that could possibly happen