• YAKHAK HOEJI
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• v.45 no.5
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• pp.506-512
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• 2001

Ketoprofen (KP) was formulated as a transdermal patch using the percutaneous penetration enhancers sorbitan monmmleate(SMO), polyvinylpyrrolidone(PVP). The control patch without penetration enhancers showed a KP flux of 8.9$\pm$0.75$\mu\textrm{g}$/$\textrm{cm}^2$/h The flux was increased in proportion to the concentration of SMO added. Furthermore, lag times were decreased upon addition of SMO. Conversely; the skin flux of KP was decreased in proportion to the concentration of PVP added. Pharmacokinetic parameters including $C_{max}$, $T_{max}$, and AUC were increased when SMO was added. However, $C_{mas}$ significantly decreased by the addition of PVP. $T_{max}$ was not significantly different in 2%, 4%, and 8% PVP patches. Patches containing 4% PVP showed the highest AUC value (19.158$\mu\textrm{g}$.h/ml). We found that the effectiveness of the two percutaneous penetration enhancers for topical KP patches was similar, with the addition of appropriate amounts of HPC modifying both skin flux and lag time of KP in the patches. In conclusion, it is possible to manufacture KP patches exhibiting high AUC, high skin flux, and short lag time using percutaneous penetration enhancers of SMO and PVP.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.36 no.2
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• pp.115-120
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• 2010

The formidable barrier property of the stratum cornemum and the high hydrophilicity of active ingredient make it difficult to permeate through the skin and reach to its site of action. The aim of this study was to investigate the effect of chemical penetration enhancers on the skin permeation of a hydrophilic cosmetic active ingredient, such as arbutin. The enhancing effects of N-methyl-2-pyrrolidone (NMP) on the permeation of a hydrophilic cosmetic active ingredient were evaluated by using Franz diffusion cell. The study indicated that NMP has considerable influence on the skin permeability. NMP was not only the most effective enhancer but also increased the skin permeability of arbutin approximately 1.3~1.5 fold compared with control without penetration enhancer. The lag time did not change with NMP, which suggested no effect of NMP on skin lipid fluidity. This suggest that arbutin co-permeated with NMP. The results indicate NMP is effective enhancer of a hydrophilic cosmetic active ingredient in penetration, with potential applications for drug delivery system.

• Applied Chemistry for Engineering
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• v.16 no.1
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• pp.15-20
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• 2005

Many scientists have been interested in drug delivery system (DDS) which improves medical treatment for curing a disease. Transdermal drug delivery (TDD) that is one of the DDS offers several advantages over the traditional methods. For this reason, the study of TDD has been investigated in various field. In this paper, principle of transdermal delivery and penetration enhancers into the skin including in vitro and in vivo data have been studied.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.224.3-225
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• 2003

Purpose. To investigate the effect of different terpene enhancers on skin penetrations of prostaglandin El (PGE1) and its ethyl ester (PGE1-EE), a therapeutic agent for erectile dysfunction, external gel systems were formulated with the specific enhancers having different values in their lipophilicity (log P was ranged in 2.23-4.58). Methods. Topical gels containing PGEl (0.5 %) and PGEl-EE (0.1 %) were formulated with ethanol and propylene glycol as a vehicle, selective terpenes as a penetration enhancer, and HPC-H as a thickening agent. (omitted)

• Journal of Pharmaceutical Investigation
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• v.31 no.4
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• pp.225-232
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• 2001

The present study was carried out to observe the effect of liposome dispersed gel formulation (Lipogel) on topical delivery of ascorbyl palmitate (AsP). Neutral and negatively charged MLV liposomes containing AsP were prepared with dimyristoylphosphadtidylcholine (DMPC) and dicetyl phosphate (DCP), and dispersed to poloxamer gel matrix. In the hydrolysis study in rat's skin homogenates, AsP hydrolyzed to ascorbic acid (AsA) according to the first-order kinetics with the rate constant of $2.46{\times}10^{-2}\;min^{-1}$. In the passive skin penetration study using Franz diffusion cell, lipogel systems exhibited the greater values in the flux $(J_s)$ and the amount penetrated $(Q_p)$ compared to control hydrogels containing diethyleneglycol monoethyl ether $(Transcutol^{\circledR})$ as a solubilizing agent and a penetration enhancer for AsP. The total amount penetrated $(Q_{Total})$, which is expressed as a summation of $Q_P\;and\;Q_L$, for lipogel system was about 1.4 times higher in average than that of control hydrogel. However the amount localized in the skin $(Q_L)$ was similar in both formulations. As a result, lipogel system enhanced the skin penetration of AsP, possibly due to the increase in local concentration of AsP by preferential adsorption of liposome to the skin and the enhancing effect of phospholipid in liposome composition. Moreover it was expected that the penetrated AsP would generate AsA during skin penetration by the skin esterase. In conclusion, lipogel formulation was considered as a good candidate for topical delivery of AsP.

• Journal of Pharmaceutical Investigation
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• v.26 no.1
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• pp.43-53
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• 1996

The objective of this study was to determine whether 4-phenylazobezyloxycarbonyl-Pro-Leu-Gly-Pro-D-Arg (Pz-peptide), an enhancer of hydrophilic solute permeability in the intestine, could elevate the paracellular permeability of hydrophilic drugs across cornea and conjunctiva in the rabbit. The in-vitro penetration of hydrophilic drugs (mannitol, atenolol) and lipophilic drug (propranolol) across the rabbit cornea and conjunctiva was studied either in the presence or absence of 3 mM Pz-peptide. Drug penetration was evaluated using the modified Ussing chamber. The conjunctiva was more permeable than the cornea to all drugs. Pz-peptide showed enhanced effects on the drug transport across cornea and conjunctiva in a concentration dependent manner. Effects or ion transport inhibitor on the mannitol penetration were then investigated. Mannitol penetration was not changed by serosal addition of $100\;{\mu}M$ ouabain, suggesting that $Na^+/K^+$ ion tranporter was not involved in the Pz-peptide induced elevation of paracellular drug permeability. Furthermore, effects of Pz-peptide and EDTA on the transport of atenolol and propranolol into the ocular tissues or blood circulation after its administration into both eyes were investigated. EDTA showed enhanced effect on propranolol transport into the ocular tissues, but Pz-peptide did not show significant difference. Systemic absorption of propranolol by the addition of EDTA or Pz-peptide was not changed. On the other hand, EDTA and Pz-peptide elavated the atenolol transport into the ocular tissues. The transport of atenolol into the blood circulation was also enhanced by the addition of EDTA, but no effect was observed by the addition of Pz-peptide. The above findings suggest that Pz-peptide would be used as an paracellular pathway enahncer of hydrophilic drugs into the eye, without affecting the systemic absortion of topically applied opthalmic drugs.

• Journal of Pharmaceutical Investigation
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• v.39 no.1
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• pp.19-21
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• 2009

This study was performed to examine the possibility of increasing the level of furosemide permeation from the ethylene-vinyl acetate (EVA) matrix through the skin by incorporating various enhancers in the EVA matrix. The effects of the enhancers on the level of furosemide permeation through the skin were evaluated using Franz diffusion cells with intact excised rat skins. The enhancers examined were the fatty acids (saturated, unsaturated), the pyrrolidones, the propylene glycol derivatives, the glycerides and the non-ionic surfactants. Among the enhancers used, polyoxyethylene-2-oleyl ether (a non-ionic surfactant) showed the best enhancement. The polyoxyethylene 2-oleyl ether as a permeation enhancer could be used for development of furosemide-EVA transdermal matrix system.

• Journal of Pharmaceutical Investigation
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• v.40 no.1
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• pp.33-38
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• 2010

Sibutramine is a serotonin-norepinephrine reuptake inhibitor indicated for the management of obesity in conjunction with a reduced calorie diet. The oral administration of sibutramine is followed by its dose-related side effects. In this study, sibutramine was formulated into drug in adhesive (DIA) patches in an attempt to overcome these problems. The effects of different formulation variables including pressure-sensitive adhesive (PSA), loading amount of drug, thickness of matrix and enhancer on the skin permeation of the drug were evaluated using excised hairless mouse skin. In the acrylic adhesive with carboxyl functional group, low release of sibutramine was observed due to the strong interaction between carboxyl group of adhesive and amine group of sibutramine. The acrylic adhesive without functional group provided good adhesion force and allowed high drug loading. Changing drug load as well as thickness of the matrix was found to alter permeation rate. $Crovol^{(R)}$ PK40 and $Crovol^{(R)}$ A40, were found to be effective enhancers for sibutramine. The optimized patch contained 20% sibutramine, and 5% $Crovol^{(R)}$ A40 as permeation enhancer, in $80\;{\mu}m$ thick Duro-$Tak^{(R)}$ 87-9301 matrix.

• Journal of Pharmaceutical Investigation
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• v.38 no.2
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• pp.87-92
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• 2008

Wood vinegar is well known as a softening agent affecting on the stratum corneum that is easy to penetrate into the skin. In this study, we prepared mixed ursolic acid hydrogel with wood vinegar(1, 2, 5%) as a penetration enhancer. The accumulation of ursolic acid in the skin from hydrogels was evaluated in vitro hairless mouse skin and skin moisturizing effect of them was evaluated using the corneometer and the tewermeter. And the role of stratum corneum as a protective barrier was evaluated as well. The hydrogels were retained about 40% of water retention capacity 2hrs and had better effect on the stripped skin than full-thickness skin. The accumulation of ursolic acid through stripped skin from hydrogels with wood vinegar was not change compared to normal skin, which indicated the action site of wood vinegar and the accumulation site of ursolic acid would be stratum corneum. From these result, we could find wood vinegar seems to be a good enhancer for active materials with anti-wrinkle and anti aging effect such as ursolic acid, and can be a developed topical delivery system maintaining excellent water retention capacity.

• Journal of Pharmaceutical Investigation
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• v.29 no.2
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• pp.111-115
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• 1999

We have studied the transdermal flux of prostaglandin $E_1$ $(PGE_1)$ from a hydrogel patch through hairless mouse skin, to test the possibility of developing a transdermal delivery system. Karaya gum patch containing $PGE_1$ was prepared by casting method. $PGE_1$ was stable in the patch for 10 weeks. The effect of current application, enhancer (propylene glycol monolaurate : PGML), adhesive and patch thickness on the flux was studied using side-by-side diffusion cell. Passive flux of $PGE_1$ was negligible. Cathodal delivery increased the flux about 20 fold. As the concentrations of PGML increased, flux increased. When 5% PGML was used as the enhancer, maximum flux by cathodal iontophoresis was $55\;{\mu}g/cm^2\;hr$. It increased about 2 folds to $100\;{\mu}g/cm^2\;hr$, when the amount of PGML used was 9%. Large increase in flux and the decrease in time to reach maximum flux were observed when the skin was pretreated with neat PGML (maximum flux obtained was about $200\;{\mu}g/cm^2\;hr$). Use of adhesive decreased the flux significantly. To the contrary of our expectation, increase in current density decreased the flux. These flux data together with the stability data indicate that, though the onset of sufficient delivery occur after 1-2 hours of application, therapeutic amount of $PGE_1$ can be delivered through skin using iontophoresis and penetration enhancer.