• Journal of Pharmaceutical Investigation
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• 제29권1호
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• pp.29-36
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• 1999

Aceclofenac is an non-steroidal antiinflammatory drug which has been used in the treatment of rheumatoidal rthritis and osteo-arthritis. In order to decrease the gastric ulcerogenic effects and contol the plasma level of aceclofenac, we have developed the transdermal delivery system of aceclofenac plaster, which were formulated employing matrix polymers of acrylates and penetration-enhancers such as $Lauroglycol^{\circledR}$, $Transcutol^{\circledR}$, oleic acid and linoleic acid. Using Franz diffusion cells mounted with a rat skin, transdermal penetration characteristics of the formulations were evaluated by the HPLC assay of aceclofenac and diclofenac, an active metabolite, in the receptor compartment of pH 7.2 phosphate buffered solution. Skin penetration was increased when the content of aceclofenac increased, showing the flux $(J,\;{\mu}g/cm^2/hr)$ of 0.37 and 2.50 for 2% and 6.75% of the content, respectively. The flux$(J,\;{\mu}g/cm^2/hr)$ from plasters made of $Durotak^{\circledR}$ 87-2074, $Durotak^{\circledR}$ 87-2510 and $Durotak^{\circledR}$ 87-2097 were 2.50, 2.77 and 4.39, respectively. $Durotak^{\circledR}$ 87-2074 showed the lowest penetration due to the carboxylic acid group in the polymer, which might form a strong hydrogen bonding with a secondary amine of aceclofenac. Although both $Durotak^{\circledR}$ 87-2510 and $Durotak^{\circledR}$ 87-2097 are amine-resistant adhesives, $Durotak^{\circledR}$ 872510 showed lower penetration than $Durotak^{\circledR}$ 87-2097 because of the hydroxyl group in $Durotak^{\circledR}$ 87-2510, which might form a weak hydrogen bonding with aceclofenac. These results reveal that the functional group in acrylic polymers would greatly affect the release of aceclofenac from the matrix, which is the rate-limiting step in the penetration of aceclofenac through rat skins. The penetration of aceclofenac from plasters using different penetration-enhancers increased in the following order: Transcutol < linoleic acid < oleic acid. And the flux from the plasters containing oleic acid as a penetrationenhancer was 2.22 times greater than that of creams, which suggest that a newly deveolped aceclofenac plaster could be used in the treatment of rheumatoidal arthritis and osteo-arthritis as an advanced transdermal delivery system.

• 대한화장품학회지
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• 제31권1호
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• pp.43-49
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• 2005

최근, 민감성 피부가 증가함에 따라 화장품의 안전성이 매우 중요시되고 있으며, 특히 방부제는 화장품 사용에 따른 부작용을 일으킬 수 있는 주요 자극원의 하나로 알려져 있다. 하지만, 방부제의 세포 독성 피부 투과, 유/수 분배, 항균력 비교 및 이를 통한 피부 자극과의 상관성 분석에 관한 연구는 전무한 실정이다. 본 연구의 목적은 상기의 여러 factor를 고려하여 화장품에서 빈번히 사용되고 있는 방부제의 하나인 phenoxyethanol을 이용한 저자극 방부시스템 개발에 관한 것이다. MTT assay를 통하여 human norm기 fibroblast cell에 대한 독성을 평가해 본 결과, 세포 독성은 propylparaben>butylparaben>ethylparaben>methylparaben>triciosan>phenoxyethanol 순으로 확인되어 phenoxyethanol이 다른 방부제에 비해 낮은 세포 독성을 나타낸 반면, 피부 일차자극을 알아보기 위하여 수행한 인체 첩포시험에서는 triclosan, methylparaben에 비해 높은 피부 자극을 나타내었다. 5 ${\~}$ 8 주령의 웅성 무모생쥐의 피부를 적출하여 in vitro Franz diffusion cell system을 이용한 방부제의 피부 투과도를 측정하여 본 결과, 피부 투과도는 phenoxyethanol > methylparaben > ethylparaben > propylparaben > butylparaben > triclosan 순으로 확인되어 세포 독성이 낮은 phenoxyethanol의 높은 피부 자극이 높은 피부 투과도와 연관성이 큰 것을 확인하였다. 따라서, 본 연구에서는 비교적 독성이 낮은 phenoxyethanol의 피부 투과도를 감소시킬 수 있는 방법을 찾고자 하였으며, 연구 결과, 제형내 polarity가 낮은 oil을 사용할 경우 phenoxyethanol의 피부 투과가 현격히 감소하며, 피부 자극도 감소함을 알 수 있었다. Oil polarity에 따른 Phenoxyethanol의 유/수 분배 측정 결과, Polarity가 낮은 oil에서는 $70\%$ 이상의 Phenoxyethanol이 수상에 존재한 반면, polarity가 높은 oil에서는 약 $70 {\~} 90\%$의 phenoxyethanol이 유상에 존재하였다. 또한, 미생물에 대한 항균력도 phenoxyethanol이 수상에 많이 존재할수록 증가하는 경향을 나타내었다. 따라서, 제형 내 oil tomposition을 변화시킴으로써 phenoxyethanol의 사용량을 줄일 수 있을 뿐만 아니라, 피부 투과를 감소시켜 보다 피부 자극이 적은 저자극 방부시스템 개발이 가능하리라 보여 진다.

• The Journal of Korean Physical Therapy
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• 제23권6호
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• pp.77-84
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• 2011

Purpose: The objectives of this study were to determine the enhancing effect of iontophoresis method as it transdermally deliver methylene blue (MB) using visual examination, in terms of penetration depth and tissue distribution in the skin, and to determine the effect of application duration on the efficacy of iontophoresis. Methods: Twenty-four male Sprague-Dawley rats were randomly divided into 5-, 10-, 20-, and 40-minute groups. These rats were exposed to either topical or anodic iontophoresis of 1% MB using a direct current of $0.5mA/cm^2$ for 5, 10, 20, and 40 minutes. Using cryosections of rat tissues, the penetration depth of MB was measured using light microscopy. Results: Significant differences in the penetration depth (F=54.20, p<0.001) were detected among the four groups. Post hoc comparisons of the penetration depth of MB data pooled across groups showed no significant difference between all topical application groups and 5-minute iontophoresis group, but did reveal a significant difference in the penetration depth between all topical application groups and 5-minute iontophoresis group versus 10-minute group, between the 10-minute and 20-minute group, and between the 20-minute and 40-minute iontophoresis group (p<0.05). Conclusion: The results demonstrate that iontophoresis enhances transdermal delivery of MB across stratum corneum of skin barrier by visual examination. Furthermore, the penetration depth of iontophoretic transdermal delivery of MB was dependent on the application duration. The duration of iontophoresis is one of the important factor in the efficacy of iontophoresis application.

• Toxicological Research
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• 제17권4호
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• pp.317-323
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• 2001

The skin penetration rate of methidathion in vitro and pharmacokinetics of methidathion in vivo were studied with male Sprague-Dawley rats by dermal treatment. The in vitro skin penetration rates for Sprague-Dawley rats of methidathion technical (50 mg, 100 ${mu}ell$) and emulsifable concentrate (EC,40mg, 100${mu}ell$) were determined as 18.4 $\mu\textrm{g}$/c $m^2$/h (RSD : 6.5) and 18.5 $\mu\textrm{g}$/c $m^2$/h (RSD : 3.2), respectively. Dose-related systemic exposure (AUC) was observed in rats after dermal treatment. The corresponding AUC, $T_{max}$, $C_{max}$, and $T_{1}$2/ of methidathion in plasma were 1.5$\mu\textrm{g}$.hr/ml, 6 h, 0.10 $\mu\textrm{g}$/ml, and 16 h, for 116mg/kg doses, 3.2 $\mu\textrm{g}$. hr/ml, 8 h, 0.12 $\mu\textrm{g}$/ml, and 23 h, for 232 mg/kg doses and 10 $\mu\textrm{g}$. hr/ml, 12 h, 0.32 $\mu\textrm{g}$/ml, and 20 h, for 1,160 mg/kg doses respectively. The urinary excretion of methidathion, estimated wing an equation derived from the in vitro skin penetration study was 0.24~0.35% of the absorbed dose. The concentration of methidathion in kidney was higher than that in liver. Dose-dependent absorption and excretion of methidathion without saturation was observed under in vivo experimental condition.n.n.

• 비파괴검사학회지
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• 제4권2호
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• pp.7-14
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• 1985

An experiment to investigate the rate of change of phase angle of eddy current output signal caused by outer surface defect of nonferromagnetic tube by variation of standard depth of penetration and variation of percent of tube wall penetration was carried out. The results of the experiment show that the phase angle of defect signal is increased with decreasing the standard depth of penetration or the depth of defect. The results also show that the phase angle is decreased with increasing the skin effect of eddy current, and that the resolution is decreased with decreasing the depth of defect.

• Archives of Pharmacal Research
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• 제24권6호
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• pp.572-577
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• 2001

The feasibility of skin penetration was studied for aspalatone (AM, acetylsalicylic acid maltol ester), a novel antithrombotic agent. In this studys hairless mouse dorsal skins were used as a model to select composition of vehicle and AM. Based on measurements of solubility and partition coefficient, the concentration of PC that showed the highest flux for AM across the hairless mouse skin was found to be 40%. The cumulative amount permeated at 48 h, however, appear inadequate, even when the PC concentration was employed. To identify a suitable absorption enhancer and its optimal concentration for AM, a number of absorption enhancers and a variety of concentration were screened for the increase in transdermal flux of AM. Amongst these, linoleic acid (LOA) at the concentration of 5% was found to have the largest enhancement factor (i.e., 132). However, a further increase in AM flux was not found in the fatty acid concentration greater than 5%, indicating the enhancement effect is in a bell-shaped currie. In a study of the effect of AM concentration on the permeation, there was no difference in the permeation rate between 0.5 and 1% for AM, below its saturated concentration. At the donor concentration of 2%, over the saturated condition, the flux of AM was markedly increased. A considerable degradation of AM was found during permeation studies, and the extent was correlated with protein concentrations in the epidermal and serosal extracts, and skin homogenates. In rat dorsal skins, the protein concentration decreased in the rank order of skin homogenate > serosal extract > epidermal extract. Estimated first order degradation rate constants were $6.15{\pm}0.14,{\;}0.57{\pm}0.02{\;}and{\;}0.011{\pm}{\;}0.004{\;}h^{-1}$ for skin homogenate, serosal extract and epidermal extract, respectively. Therefore, it appeared that AM was hydrolyzed to some extent into salicylmaltol by esterases in the dermal and subcutaneous tissues of skin. taken together, our data indicated that transdermal delivery of AM is feasible when the combination of PC and LOA is used as a vehicle. However, since AM is not metabolically stable, acceptable degradation inhibitors may be nervessary to fully realize the transdermal delivery of the drug.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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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)

• 약학회지
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• 제44권6호
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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.

• 대한화장품학회지
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• 제47권2호
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• pp.133-138
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• 2021

본 연구에서는 기능성 미백물질인 나이아신아마이드(NI)의 피부 투과율을 개선시키기 위해 NI를 고형지질 나노입자(solid lipid nanoparticles, SLNs))에 봉입하고 피부 투과율을 평가하였다. NI는 이중 에멀션 가온용융 유화법으로 SLNs 내에 효과적으로 봉입할 수 있었으며, 평균 입자 크기는 263.30 ~ 436.93 nm이었고 제타전위는 -34.77 ~ -57.60 mV인 안정한 입자를 제조하였다. NI의 피부 투과 연구를 위해 인체 표피 조직에서 유래된 피부각질세포로 만든 3차원적 인공피부(SkinEthic^TM RHE)을 사용하였다. NI의 피부 투과 및 침적 실험 결과 모든 SLNs 제형이 NI의 피부 투과 및 침적율을 개선시켰으며, SLNs을 적용하였을 때가 그렇지 않을 때 보다 투과율은 약 5.4 ~ 7.6 배, 침적율은 9.5 ~ 20.8 배 개선되었을을 확인하였다. 따라서, 본 연구에서 제조된 고형지질나노입자는 기능성 미백물질인 나이아신아마이드의 피부 투과율을 개선하기에 충분한 결과를 보여 주었다.

• Journal of Pharmaceutical Investigation
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• 제31권4호
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• pp.217-224
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• 2001

To develop a novel transdermal delivery system of loxoprofen (LP), a potent antiinflammatory and analgesic agent, the effects of various vehicles and penetration enhancers on the skin permeation of LP from solution formulations were investigated. The permeation rate of LP through excised guinea pig skin was measured using a side-by-side permeation system at $32^{\circ}C$. The solubilities of LP in various vehicles were determined by the equilibrium solubility method, and partition coefficients $(P_c)$ were determined. The solubility of LP increased in the rank order of water & isopropyl myristate (IPM) & glyceryl dicaprylate/dicaprate & propylene glycol dicaprylate/caprate & propylene glycol laurate (PGL) & polyethylene glycol 400 & diethylene glycol monoethyl ether (DGME) & ethanol. n-Octanol-water $P_c$ value was 15.5. Among pure vehicles tested, IPM and PGL showed highest fluxes of $89.9{\pm}5.0$ and $45.4{\pm}0.3\;{\mu}g/cm^2/hr$ from saturated solutions, respectively. However, it was not possible to demonstrate any correlation between the solubility of LP and its permeation rate, indicating the change in the barrier property of the skin and/or carrier mechanisms by vehicles tested. The addition of DGME to IPM or PGL markedly increased the solubility of LP, but the permeation rate did not decrease when the concentration of DGME in the cosolvent was increased upto 40%. The addition of linoleic acid (3%) in the cosolvent slightly increased the permeation rate, but others such as lauroyl sarcosine, fatty alcohols and fatty acids tested did not show enhancing effect. In conclusion, the DGME-IPM or DGME-PGL cosolvent system proved to be a good vehicle to enhance the skin permeation of LP.