• Biomolecules & Therapeutics
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• 제19권1호
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• pp.109-117
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• 2011

In this work, we have investigated the effect of polyoxyethylene alkyl ester nonionic surfactants on percutaneous permeation enhancement of a model drug, ketoprofen. We also investigated the mechanism involved in the enhancement using impedance and solubility measurement. Three groups of nonionic surfactants with different ethylene oxide content were studied. The permeation results showed that all surfactants enhanced the percutaneous absorption, irrespective of the molecular weight. The permeation results from PEG-45 monostearate (PEGMS45) were rather unexpected. Impedance and solubility results indicate that the mechanism involved in the enhancement of permeation by PEG-10 monooleate (PEGMO10) and PEGMS45 is rather different. The results from PEGMS45 suggest that it could be a potential candidate as a skin penetration enhancer with high molecular weight, which may poses less skin irritation and systemic side effect than the smaller surfactant molecules. Overall, this work provided some useful information on percutaneous transport enhancement and the mechanistic insights involved in skin permeation for these nonionic surfactants.

• 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.

• 약학회지
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• 제43권4호
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• pp.447-457
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• 1999

The purpose of this study is to prepare the adhesive type patch containing flurbiprofen, and to demonstrate the feasibility of flurbiprofen administration through the intact skin using adhesive type patch preparation. For this purpose, two pressure sensitive adhesives, Polyisobutylene(PIB) and $Gelva^{\circledR}737$, were selected from the chemical grade of polymers, and the adhesive type patches of flurbiprofen were prepared. The release rate of flurbiprofen from the PIB-based adhesive patch was higher than that from $Gelva^{\circledR}737$ based adhesive patch. The release rate of flurbiprofen from the PIB-based A-type patch with 1.0mm, 1.5mm or 2.0mm thicknesses followed the first order kinetics. In the skin permeation study, using male hairless mouse skin, a monophasic skin permeation profile was observed with 1% flurbiprofen loading dose. The inclusion of palmitic acid or SLS(0.25~0.5%) as an enhancer produced a remarkable enhancement in the skin permeation rate of flurbiprofen, and the percentile ratio of drug and enhancer appeared to be important for the effective enhancement. In the in vivo percutaneous absorption study, the plasma concentration of the optimal formulation was significantly (p<0.01) higher than that of the conventional cataplasma ($Bifen^{\circledR}$). These studies demonstrate a good feasibility of flurbiprofen administration through the intact skin using a transdermal patch, and show a possibility of the development of flurbiprofen patches.

• 한국응용과학기술학회지
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• 제28권2호
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• pp.170-177
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• 2011

Transdermal drug delivery(TDS) offers many important advantages. For instance, it is easy and painless, it protects the active compound from gastric enzymes, and it avoids the hepatic first-pass effect. Also, it is simple to terminate the therapy if any adverse or undesired effect occurs. But skin is a natural barrier, and only a few drugs can penetrate the skin easily and in sufficient quantities to be effective. Therefore, in recent years, numerous studies have been conducted in the area of penetration enhancement. The most commonly used transdermal system is the skin patch using various types of technologies. Compared with other method of dosage, it is possible to use for a long term. It is also possible to stop the drug dosage are stopped if the drug dosage lead to side effect. Polysaccharide, such as xanthan gum and algin were selected as base materials of TDS. Also, these polymers were characterized in terms of enhancers and drug contents. Among these polysaccharide, the permeation rate of Paroxetine such as lipophilic drug was the fastest in xanthan gum matrix in vitro. We used glycerin, PEG400 and PEG800 as enhancers. Since dermis has more water content(hydration) than the stratum corneum, skin permeation rate at steady state was highly influenced when PEG400 was more effective for lipophilic drug. Proper selection of the polymeric materials which resemble and enhance properties of the delivering drug was found to be important in controlling the skin permeation rate.

• 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)

• Journal of Pharmaceutical Investigation
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• 제28권3호
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• pp.165-169
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• 1998

The effect of various vehicles on the permeation of a model drug, ketoprofen in solution formulation was evaluated using a flow-through diffusion cell system at $37^{\circ}C$. To investigate the mechanism of permeation rate enhancement, the effects of pretreatment with various vehicles on the permeation of the drug were evaluated using 5 mg/ml solution and saturated solution. The order of permeation rate of ketoprofen across hairless mouse skin after pretreatment with various vehicles was similar to the case where the vehicles and the drug were coadministered except ethanol and oleic acid. The results indicate that the mechanism of enhancement can be direct action of the vehicles on the barrier property of the skin and/or carrier mechanism.

• Journal of Pharmaceutical Investigation
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• 제33권2호
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• pp.79-84
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• 2003

The effects of various pressure sensitive adhesives (PSA) and enhancers on the percutaneous absorption of tulobuterol were investigated. The permeation rate of tulobuterol through hairless mouse skin from various adhesives was evaluated using a flow-through diffusion cell system at $37^{\circ}C$. The permeability of tulobuterol was variable depending on the physicochemical property of the PSA. The permeation rate of tulobuterol from polyethylene oxide grafted acrylic adhesive matrix was higher than that from other PSA matrices. The flux of tulobuterol was $4.37{\pm}0.34\;{\mu}g/hr/cm^2$ from polyethylene oxide grafted acrylic adhesive matrix. When the effects of various enhancers on the percutaneous absorption of tulobuterol from grafted acrylic adhesive were evaluated, Plurol $oleique^{\circledR}$ showed higher flux than all other enhancers tested.

• Journal of Pharmaceutical Investigation
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• 제25권3호spc1호
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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.

• 한국응용과학기술학회지
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• 제36권3호
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• pp.853-865
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• 2019

본 연구에서는 경피 흡수가 어려운 주름 개선 펩티드인 GHK, GHK-Cu, Pal-GHK 리포좀 및 여기에 피부 투과 펩티드인 아르지닌 올리고머 R4(tetra-D-arginine), R6(hexa-D-arginine)를 첨가한 리포좀으로 경피 투과도를 측정하여 그 결과를 다음 6가지 구분으로 분석하였다. (1) 주름 개선 펩티드만 함유한 GHK, GHK-Cu, Pal-GHK lioposome의 경우; 24시간 최종 누적 경피 투과율은 6.05%, 7.4%, 8.83%를 보였다. (2) GHK에 약물 전달 펩티드 아르지닌 올리고머 R4, R6를 첨가한 리포좀의 경우; 24시간 최종 누적 경피 투과율은 13.63%, 7.68%를 나타냈다. (3) GHK-Cu에 R4, R6를 첨가한 리포좀의 경우; 24시간 최종 누적 경피 투과율은 15.46%, 8.64%로 나타났다. (4) Pal-GHK에 R4, R6를 첨가한 리포좀의 경우; 24시간 최종 누적 경피 투과율은 16.9%, 10.67%를 보였다. (5) GHK, GHK-Cu, Pal-GHK에 각각 R4를 첨가한 리포좀의 경우; 24시간 최종 누적 경피 투과율은 13.63%, 15.46%, 16.9%를 나타냈다. (6) GHK, GHK-Cu, Pal-GHK에 각각 R6를 첨가한 리포좀의 경우; 24시간 최종 누적 경피 투과율은 7.68%, 8.64%, 10.67%로 나타났다. 본 실험을 통해 구리이온(Cu2+)과 팔미트산에 의해 GHK의 피부 흡수가 증가하고, 피부 투과 펩티드에 의해 주름 개선 펩티드의 피부 흡수가 증진되며, GHK, GHK-Cu, Pal-GHK에는 R4가 R6보다 높은 효과를 보이는 것을 알 수 있었다. 이를 통하여 GHK, GHK-Cu, Pal-GHK의 피부 흡수를 증가를 위한 최적의 조건을 제시하여 그 효능을 극대화할 수 있는 방안을 제시함으로써 주름 개선 기능성 화장품에서의 폭넓은 활용과 응용을 제안한다.

• 분석과학
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• 제21권3호
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• pp.222-228
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• 2008

생체피부에서의 잠재지문 현출에는 많은 제한점이 있다. 살아있는 피부는 계속적인 발한을 하고 지방친화성이 있어 흡수 및 확산에 의해 지문변화를 초래하기 때문이다. 본 연구는 사람피부에 존재하는 잠재지문의 효과적 현출방법을 알아보기 위하여 살아있는 생체피부와 피부유사 돼지피부를 이용하여 수행되었다. 피부지문현출제로는 흑색, 형광 분말 및 자석분말 그리고 Cyanoacrylate fuming을 이용하였으며 전사법으로는 전사지(lifting paper), 유리, 사진현상용 glossy paper를 이용하여 피부로부터 전사한 후 현출하였다. 살아있는 피부에 존재하는 즉시지문일 경우에는 흑색분말인 S-powder, Cyanoacrylate fuming법 및 훈증후 흑색 또는 형광분말로의 재처리에 의해 현출이 가능하였고 자석분말로의 현출로는 지문이나 배경피부에 과도하게 흡착되는 경향을 볼 수 있었으며 유류에 따라 지문이 사라짐을 알 수 있었다. 사체유사 돼지피부에서는 6시간 유류된 지문에서도 $25^{\circ}C$, 40%에서 1분간의 Cyanoacrylate fuming법 이후 흑색분말로의 재현출하였을 때 잠재지문의 현출이 가능함을 알 수 있었으며 현출된 지문영상에 다양한 스펙트럼을 이용한 감식영상의 효과적 조사파장에 대한 결과를 얻을 수 있었다.