• Archives of Pharmacal Research
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• v.25 no.1
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• pp.86-92
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• 2002

The enhancement of paracellular transport of heparin disaccharide using several absorption enhancers across Caco-2 cell monolayers was tested . The cytotoxicity of these enhancers was also examined. The enhancing effects by Quillaja saponin, diponin glycyrrhizinate, $18{\beta}-glycyrrhetinic$ acid, sodium caprate and taurine were determined by changes in transepithelial electrical resistance (TEER) and the amount of heparin disaccharide transported across Caco-2 cell monolayers. Among the absorption enhancers, $18{\beta}-glycyrrhetinic$ acid arid taurine decreased TEER and increased the permeability of heparin disaccharide in a dose-dependent and time-dependent manner with little or negligible cytotoxicity. Our results indicate that these absorption enhancers can widen the tight junction, which is a dominant paracellular absorption route of hydrophilic compounds . It is highly possible that these absorption enhancers can be applied as pharmaceutical excipients to improve the transport of macromolecules and hydrophilic drugs having difficulty in permeability across the intestinal epithelium.

• Journal of Pharmaceutical Investigation
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• v.33 no.2
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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 the Korean Applied Science and Technology
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• v.29 no.4
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• pp.552-560
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• 2012

Drug delivery technologies are patent protected formulation technologies that modify drug release profile, absorption, distribution, and elimination for the benefit of improving product efficacy and safety, as well as patient convenience and compliance. 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 stop if the drug dosage lead to side effect. Polysaccharide, such as karaya gum and locust bean gum(LBG)/water-soluble chitosan oligomer(WSCO) were selected as base materials of TDS. Also, these polymers were characterized in terms of enhancers, tacrine contents. Among these polysaccharide, the permeation rate of karaya gum matrix was fastest in tacrine such as lipophilic drug in vitro. We used glycerin, PEG 400, and PEG 800 as enhancers. Therefore, transdermal absorption of tacrine could be improved by changing vehicle composition or by using penetration enhancers. Especially it would be anticipated that the high permeation efficacy could be obtained by using vehicle that has enhancing effect for itself and by adding enhancers to it.

• Proceedings of the PSK Conference
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• 2000.04a
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• pp.214.1-214.1
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• 2000

• 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)

• Journal of Pharmaceutical Investigation
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• v.37 no.3
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• pp.173-177
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• 2007

The purpose of this study was to investigate the effect of salt formation on the percutaneous absorption of meloxicam through hairless mouse skin from a pressure sensitive adhesive (PSA) matrix. In addition, the influences of enhancers on the permeation of meloxicam or meloxicam-ethanolamine (MX-EA) salts across the hairless mouse skin were evaluated using a flow-through diffusion cell system. The salt formation of meloxicam resulted in lower permeation rate than the parent drug. $Span^{(R)}$ 80 provided the highest enhancing effect for meloxicam and meloxicam monoethanolamine salt. The maximum amount of the drug that can be loaded without retarding permeation rate was different depending on the compound. No relationship was found between the fluxes of meloxicam or MX-EA salts from saturated solutions and those from PSA matrices containing the same enhancer.

• Journal of Pharmaceutical Investigation
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• v.31 no.2
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• pp.107-112
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• 2001

In order to reduce the systemic side effects and gastrointestinal irritation after its oral adminitration, ketoprofen was formulated as water-soluble packs. The effects of fatty acids and fatty alcohols on the penetration of ketoprofen through excised rat skins were evaluated. The role of stratum corneum as a protective barrier was also investigated. Fatty acids and fatty alcohols were generally effective in promoting ketoprofen penetration. The flux of ketoprofen through rat skin was maximized when oleic acid or lauryl alcohol was used as an enhancer. As the concentration of fatty acids and fatty alcohols varied from 0% to 10%, the amounts of ketoprofen penetrated were in direct proportion to that of fatty acids but those had no relationship with that of fatty alcohols. The penetration of ketoprofen through stripped skin was enhanced compared to normal skin irrespective of enhancer type, which indicated that the action site of enhancers would be stratum corneum.

• Archives of Pharmacal Research
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• v.24 no.6
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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.

• Journal of Pharmaceutical Investigation
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• v.29 no.2
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• pp.137-143
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• 1999

Ketoprofen together with various permeation enhancers was incorporated into a novel soft hydrogel which is semi-solid in a container and to form a thin film within a few minutes after applying on the skin. The effect of various enhancers on the skin permeation of ketoprofen from a soft hydrogel was investigated using in vitro and in vivo method. In vitro rat skin permeation of ketoprofen from soft hydrogel was conducted using modified Keshary-Chien diffusion cells. In vivo ketoprofen absorption was also investigated in rats, and the results were compared with that of commercial products. Anti-inflammatory activities were determined using carrageenan-induced paw edema method and adjuvant-induced arthritis method in rats. The anti-inflammatory activity of ketoprofen soft hydrogel formulation with that of commercial products were compared. In vitro as well as in vivo studies showed that $HPE-101^{\circledR}$ was the most effective skin permeation enhancer among those used in this study. Addition of an adhesive (polyisobutylene) in the soft hydrogel decreased skin permeation of ketoprofen. Paw edema and anti-arthritis tests showed that soft hydrogel containing $HPE-101^{\circledR}$ was more effective than the commercial products, which was consistent with the in vivo absorption experiment results.