• Journal of Pharmaceutical Investigation
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• v.41 no.6
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• pp.347-354
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• 2011

Repeated oral administration of loxoprofen can induce many side effects such as gastric disturbances and acidosis. Therefore, we considered alternative routes of administration for loxoprofen to avoid such adverse effects. The aim of this study was to develop an ethylene-vinyl acetate (EVA) matrix system containing a permeation enhancer for enhanced transdermal delivery of loxoprofen. The EVA matrix containing loxoprofen was fabricated and the effects of drug concentration, temperature, enhancer and plasticizer on drug release were studied from the loxoprofen-EVA matrix. The solubility of loxoprofen was highest at 40% (v/v) PEG 400. The release rate of drug from drug-EVA matrix increased with increased loading dose and temperature. The release rate was proportional to the square root of loading dose. The activation energy (Ea), which was measured from the slope of log P versus 1000/T, was 5.67 kcal/mol for a 2.0% loaded drug dose from the EVA matrix. Among the plasticizer used, diethyl phthalate showed the highest release rate of loxoprofen. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the greatest enhancing effect. In conclusion, for the enhanced controlled transdermal delivery of loxoprofen, the application of the EVA matrix containing plasticizer and penetration enhancer could be useful in the development of a controlled drug delivery system.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.230.1-230.1
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• 2003

In case of oral application of quinupramine, antidepressants, it may cause adverse effects such as diarrhea, nausea due to transient high blood concentration. Ethylene vinyl acetate (EVA) which is heat-processible, flexible, inexpensive material was used for transdermal drug delivery. The purpose of this study was to develop the new transdermal delivery system of quinupramine using EVA polymer matrix that can provide sustained release and avoid the side effects. The EVA matrix containing quinupramine was prepared by solvent-evaporation method. (omitted)

• Journal of Pharmaceutical Investigation
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• v.40 no.3
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• pp.167-173
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• 2010

Repeated oral administration of hydrochlorothiazide, a loop diuretic, due to transient high blood levels, may cause adverse effects such as gastric disturbance, nausea, high blood sugar, and hyper lipidemia. Transdermal administration could avoid some of these systemic side effects and gastric disorders. We have developed a matrix using ethylene-vinyl acetate (EVA), a heat-processible and flexible material, for transdermal delivery of hydrochlorothiazide. Drug solubility was highest at 40% PEG-400 volume fraction. Drug release increased as concentration increased with a linear relationship between the release rate and the square root of loading dose. Increasing temperature increased drug release from the EVA matrix. The activation energy, measured from the slope of log P versus 1000/T, was 11.9 kcal/mol for a 2.5% loading dose from EVA matrix. Diethyl phthalate had the highest plasticizing effects on the release of hydrochlorothiazide. To increase the skin permeation of hydrochlorothiazide from the EVA matrix, enhancers such as the saturated fatty acids, the unsaturated fatty acids, and the non-ionic surfactants were added to the EVA matrix, and skin permeation was evaluated using a modified Keshary-Chien diffusion cell fitted with intact excised rat skin. Polyoxyethylene 23-lauryl ether showed the highest enhancing effects. In conclusion, transdermal delivery of hydrochlorothiazide could be improved from an EVA matrix containing plasticizer and permeation enhancer.

• 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 the Korean Chemical Society
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• v.37 no.5
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• pp.527-536
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• 1993

The characteristics of the controlled drug release were studied for biodegradable transdermal drug delivery system. A biodegradable polymeric matrix was prepared from chitosan, silver sulfadiazine, and glycerine. The release behavior of silver sulfadiazine from chitosan matrix was consistent with the Higuchi's diffusion controlled model. The release time was delayed by increasing the content of silver sulfadiazine and thickness of the matrix, whereas decreased as glycerine concentration increased. The apparent constant (K) of release rate was proportional to the content of drug or glycerine and the thickness of chitosan matrix. These results indicated that chitosan matrix shows some potential as a drug delivery system for transdermal therapeutic application.

• Journal of Pharmaceutical Investigation
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• v.27 no.4
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• pp.303-311
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• 1997

Proliposomal patch of clenbuterol, ${\beta}_2-agonist$ bronchodilator, was prepared and its feasibility as a novel transdermal drug delivery system was examined. Proliposomal granules containing clenbuterol was prepared by a standard method using sorbitol and lecithin with (Rx 2) or without cholesterol (Rx 1). The porous structure of sorbitol in the proliposomes was maintained allowing tree flowability of the granules. Following contact with water, the granules were converted probably to liposomes almost completely within several minutes. It indicates that proliposomes may be hydrated, when they are applied on the skin under occlusive condition in vivo, by the sweat to form liposomes. Clenbuterol release from Rx 1 and Rx 2 proliposomes to pH 7.4 isotonic phospate buffer (PBS) across cellulose membrane (mol. wt. cut-off of 12000-14000) was retarded significantly compared with that from the mixture of clenbuterol powder and blank proliposomes. Interestingly, proliposomes prepared with lecithin and cholesterol (i.e., Rx 2 proliposomes) showed much more retarded release of clenbuterol than proliposomes prepared only with lecithin (i.e.. Rx 1 proliposomes), indicating that clenbuterol release from proliposomes can be controlled by the addition of cholesterol to the proliposomes. Proliposomal patches were prepared using PVC film as an occlusive backing sheet, two sides adhesive tape (urethane, 1.45 mm thickness) as a reservoir for proliposome granules and Millipore MF-membrane (0.45 mm pore size) as a drug release-controlling membrane. Rx 1 or Rx 2 proliposomes containing 4.6 mg of clenbuterol were loaded into the reservoir of the patch. Clenbuterol release from the patches to pH 7.4 PBS was determined using USP paddle (50 rpm)-over-disc release method. Clenbuterol release from the proliposomal patches was much more retarded even than from a matrix type clenbuterol patch (Boehringer Ingelheim ltd). Being consistent with clenbuterol release from the proliposomal granules, the release from the patches was highly dependent on the presence of cholesterol in the proliposomes : Patches containing Rx 2 proliposomes showed several fold slower drug release than patches containing Rx 1 proliposomes. When the patch containing Rx 1 proliposomes was applied on to the back of a hair-removed rat, clenbuterol concentration in the rat blood was maintained during 6-72 hrs. Transdermal absorption of clenbuterol from the patch was accelerated when the patch was prehydrated with 50 ml of pH 7.4 PBS before topical application. Above results indicate that sustained transdermal delivery of clenbuterol is feasible using proliposomal patches if the cholesterol content and pore size of the release rate-controlling membrane of patches, for example, are appropriately controlled.

• Journal of Pharmaceutical Investigation
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• v.25 no.3
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• pp.53-59
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• 1995

Ethinylestradiol (EE)-containing matrix was fabricated with ethylene-vinyl acetate(EVA) copolymer to control the release of the drug, Effect of addition of PEG 400 as receptor solution, the stripping of skin and Azone pretreatment on skin on the permeation of EE through the excised mouse skin was also studied. The permeation rate of EE through the excised mouse skin was affected by the PEG 400 volume fraction. The Azone pretreatment on skin didn't affect on the steady state flux, however, the lag time was shortened. The permeation rate of EE through the stripped skin was much larger than that through the whole skin. It showed that the stratum corneum acts as a barrier of skin permeation. The fact that there is little difference in EE permeation between the intact skin and the stripped skin with EVA membrane shows the permeation of EE through the mouse skin is mainly controlled by the membrane.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.131-131
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• 1995

제제설계 및 컴퓨터 최적화기법을 응용하여 고형으로 바뀌는 Gel화 시간이 가장 짧은 기본처방을 구하고, Indomethacin을 주 약물로하여 약물방출에 영향을 줄 수 있는 PVA, PEG 및 Ethanol 을 독립변수로, 약물방출속도를 종속변수로 하여 중심 합성계획법에 따라 실험을 행하여 최적처방을 구한다. 최적처방에 의한 Soft Hydrogel 을 제조하여 약물방출속도 및 Rheometer 에 의한 유동특성을 측정하였다.

• Polymer(Korea)
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• v.37 no.3
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• pp.347-355
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• 2013

In this study, the porous cellulose hydrogel as a carrier to enhance the skin delivery of quercetin and its glycoside, rutin known as flavonoid antioxidants was prepared and its properties were investigated. The optimum cellulose hydrogel for quercetin and rutin was made by the reaction of 2 wt% cellulose with 12% ECH. In the release test of the hydrogel containing the flavonoids, the release of quercetin was diffusion-controlled at $10{\sim}500{\mu}M$, but rutin was released by the erosion of hydrogel system at $10{\sim}50{\mu}M$. Both the encapsulation efficiency and release amount of rutin in hydrogel were higher than quercetin. However, in skin permeation experiment using Franz diffusion cell, quercetin showed higher skin permeation capacity than rutin. The hydrogel containing flavonoids showed remarkable transdermal permeation than the control group. These results suggest that porous cellulose hydrogel is potential drug delivery system to enhance transdermal permeation of water-insoluble flavonoid antioxidants.

• Archives of Pharmacal Research
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• v.27 no.7
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• pp.763-768
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• 2004

To investigate the feasibility of developing a new quercetin transdermal system, a preformulation study was carried out. Therefore, the effects of vehicles and pressure-sensitive adhesives (PSA) on the in vitro permeation of quercetin across dorsal hairless mouse skin were studied. Among vehicles used, propylene glycol monocaprylate (PGMC) and propylene glycol mono-laurate were found to have relatively high permeation flux from solution formulation (i.e., the permeation fluxes were 17.25$\pm$1.96 and 9.60$\pm$3.87 $\mu\textrm{g}$/$\textrm{cm}^2$/h, respectively). The release rate from PSA formulations followed a matrix-controlled diffusion model and was mainly affected by the amount of PSA and drug loaded. The overall permeation fluxes from PSA formulations were less than 0.30 $\mu\textrm{g}$/$\textrm{cm}^2$/h, which were significantly lower compared to those obtained from solution formulations. The lower permeation fluxes may be due to the decrease of solubility and diffusivity of quercetin in the PSA layer, considering the fact that the highest flux of 0.26 $\mu\textrm{g}$/$\textrm{cm}^2$/h was obtained with the addition of 0.2％ butylated hydroxyanisole in PGMC-diethyl-ene glycol monoethyl ether co-solvents (80-85 ： 15-20, v/v). Taken together, these observations indicate that improvement in the solubility and diffusivity of quercetin is necessary to realize fully the clinically applicable transdermal delivery system for the drug.