• Journal of Pharmaceutical Investigation
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• v.33 no.1
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• pp.29-36
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• 2003

Clenbuterol, a selective ${\beta}_2-adrenergic$ receptor stimulant, has been introduced as a potent bronchodilator for patients with bronchial asthma, chronic obstructive bronchial disease, chronic bronchitis and pulmonary emphysema. The percutaneous permeation of clenbuterol was investigated in hairless mouse skin after application of 50/50 buffer(pH 10)/propylene glycol solvent mixture. The enhancing effects of various penetration enhancers such as terpenes, non-ionic surfactants, pyrrolidones, fatty acids and some other enhancers on the permeation of clenbuterol were evaluated using Franz diffusion cell. Among terpenes studied, 1,8-cineole was the most effective enhancer, which increased the permeability of clenbuterol approximately 39.33-fold compared with the control without penetration enhancer, followed by menthone with enhancement ratio of 23.57. Nonionic surfactants did not have significant enhancing effects. N-Lauryl-2-pyrrolidone increased the permeability of clenbuterol approximately 4.51-fold compared with the control. Lauric acid increased the permeability of clenbuterol approximately 35.57-fold with decreasing the lag time from 2.64 to 0.52 hr. Oleic acid, linoleic acid, linolenic acid and capric acid showed enhancement ratio of 22.62, 19.60, 17.45 and 16.51, respectively. $Labrafil^{\circledR}$ enhanced the permeability of clenbuterol 9.24-fold compared with that without enhancer.

• Archives of Pharmacal Research
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• v.26 no.11
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• pp.973-978
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• 2003

A polymeric film composed of Carbopol, Poloxamer and hydroxypropyl methylcellulose was prepared to develop a buccal patch and the effects of composition of the film on adhesion time, swelling ratio, and dissolution of the film were studied. The effects of plasticizers or penetration enhancers on the release of triamcinolone acetonide (TAA) were also studied. The hydrogen bonding between Carbopol and Poloxamer played important role in reducing swelling ratio and dissolution rate of polymer film and increasing adhesion time. The swelling ratio of the composite film was significantly reduced and the adhesion time was increased when compared with Carbopol film. As the ratio of Poloxamer to hydroxypropyl methylcellulose increased from 0/66 to 33/33, the release rate of TAA decreased. However, no further significant decrease of release rate was observed beyond the ratio of 33/33. The release rate of TAA in the polymeric film containing polyethylene glycol 400, a plasticizer, showed the highest release rate followed by triethyl citrate, and castor oil. The release rate of TAA from the polymeric film containing permeation enhancers was slower than that from the control without enhancers. Therefore, these observations indicated that a preparation of a buccal patch is feasible with the polymeric film composed of Cabopol, Poloxamer and hydropropyl methylcellulose.

• Archives of Pharmacal Research
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• v.25 no.3
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• pp.392-399
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• 2002

The effects of vehicles and penetration enhancers on the in vitro permeation of melatonin through dorsal hairless mouse skin were investigated. Propylene glycol laurate (PGL), isopropyl myristate (IPM), propylene glycol monolaurate (PGML) and propylene glycol monocaprylate (PGMC) showed high permeation fluxes and PGL, PGML and PGMC decreased lag time significantly. In both of the binary co-solvents of diethylene glycol monoethyl ether (DGME)-PGL and DGME-IPM, the highest fluxes were achieved at 20% of DGME, which were $10.5{\pm}1.5$ and $9.1{\pm}2.4{\;}{\mu\textrm{g}}/cm^2/h$, respectively. Among fatty acids used as a permeation enhancer, capric acid and oleic acid in DGME-PGL (80:20 v/v) showed relatively high enhancing effects. Capric acid also shortened the lag time of melatonin from $2.4{\pm}0.7{\;}to{\;}1.3{\pm}0.2{\;}h$. Oleic acid, however, failed to shorten the lag time. Therefore, for effective solution formulations in terms of permeation flux and lag time, capric acid-containing DGME-PGL (80 : 20 v/v) could be used to enhance the skin permeation of melatonin.

• Journal of Pharmaceutical Investigation
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• v.34 no.4
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• pp.275-281
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• 2004

We have studied the effect of polarity, current density, current duration, crosslinking density, swelling ratio, and permeation enhancers on the transdermal flux of ketoprofen from acrylamide hydrogel. Hydrogel was prepared by free radical crosslinking polymerization of acrylamide. Drug loading was made just before transport experiment by soaking the hydrogel in solution containing drug. In vitro flux study using hairless mouse skin was performed at $36.5^{\circ}C$ using side-by-side diffusion cell, and the drug was analysed using HPLC/UV system. The result showed that, compared to passive flux, the total amount of drug transported increased about 18 folds by the application of $0.4\;mA/cm^2$ cathodal current. Anodal delivery with same current density also increased the total amount of drug transported about 13 folds. It seemed that the increase in flux was due to the electrorepulsion and the increase in passive permeability of the skin by the current application. Flux increased as current density, the duration of current application and loading amount (swelling duration) increased. As the cross linking density of the hydrogel increased, flux clearly decreased. The effect of hydrophilic enhancers (urea, N-methyl pyrrolidone, Tween 20) and some hydrophobic enhancers (propylene glycol monolaurate and isopropyl myristate) was minimal. However, about 3 folds increase in flux was observed when 5% oleic acid was used. Overall, these results provide some useful information on the design of an optimized iontophoretic delivery system of ketoprofen.

• Proceedings of the PSK Conference
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• 2001.04a
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• pp.228.1-228.1
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• 2001

• 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.

• 한국생물공학회:학술대회논문집
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• 2005.10a
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• pp.816-820
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• 2005

Polysaccharide-based dressings have increasingly become viable alternatives to somewhat less biocompatible and often problematic cotton or viscose gauzes traditionally used for wound dressings. Polysaccharide which is particularly abundunt in Agaricus blazei Murill is known as the bioactive materials. Polysaccharide extracted from Agaricus blazei Murill enhances the recovery of the damaged epidermal tissue and the production of epithelial cell growth factors which are necessary to heal the burn and wound on the epidermal tissue. In this study, the biopolymer delivery system of polysaccharide extracted from Agaricus blazei Murill into epidermal tissue was elucidated using the skin permeating enhancer in vitro. The enhancing effects of various penetration enhancers and some other enhancers on the permeation of ${\beta}-glucan$ were evaluated using Franz diffusion cell. Permeation of polysaccharide in nomal and burn skin was compared. Polysaccharide was studied for the burn and wound healing activity in the epidermal tissue on rats.

• Biomolecules & Therapeutics
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• v.5 no.4
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• pp.357-363
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• 1997

The effects of formulation variables of topical lotion on the skin permeation of ketoprofen were evaluated using excised rat skins. The formulation variables were the amounts of poloxamer 407, drug and ethanol, and penetration enhancers. The Keshary-Chien diffusion cells were used for the diffusion study. The flux of ketoprofen linearly decreased as the concentration of poloxamer increased from 5% to 15% in the preparation, and linearly increased as the amount of drug increased. Penetration enhancers such as fatty acids and fatty alcohols showed markedly enhancing effects at the level of 5%. Among them, the highest flux was shown in linolenic acid. From these results, optimum formula containing 3% ketoprofen, 5% poloxamer 407, 40% ethanol and 5% linolenic acid having the flux of 537.6 $\mu$g/$\textrm{cm}^2$/hr were noted.

• Journal of Environmental Health Sciences
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• v.26 no.2
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• pp.91-96
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• 2000

We investigated characters of transdermal therapeutic system(TTS) and the skin permeability of that with applying drug delivery system(DDS). Natural gums were selected as material of TTS. The permeation of natural gums ointment containing drug in rat skin using diffusion cell model. Permeation properties of materials were investigated for water soluble drug such as riboflavin in vitro. We used glycerin, PEG 600 and oleic acid as enhancers. Since dermis has more hydration than the stratum corneum, skin permeation rate at steady state was highly influenced when glycerin was used in riboflavin. The permeation rate of content enhancer and drug was found to be faster than that of content riboflavin only. These results showed that skin permeation rate of drug across the composite was mainly dependent on the property of ointment base and drug. All the gum ointment tested showed good safety. Proper selection of the materials which resemble and enhance properties of the delivering drug was found to be important in controlling the skin permeation rate.

• 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)