• Journal of Pharmaceutical Investigation
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• v.27 no.4
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• pp.271-277
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• 1997

Because omeprazole(OMP) is very unstable in aqueous condition, $OMP-{\beta}-CD$, the inclusion complex of OMP and ${\beta}-cyclodextrin({\beta}-CD)$ was made and physicochemical properties of it were compared with those of OMP. Skin permeability of OMP and $OMP-{\beta}-CD$ in propylene glycol vehicle and the reciprocal action of ${\beta}-CD$ with various enhancers were examined through hairless mouse. Adhesive patches were prepared with polyisobutylene and the skin permeability and stability of OMP were investigated. The inclusion complex showed higher solubility and lower partition coefficient than OMP itself. DMSO, 1-methyl 2-pyrrolidone and sodium cholate had an enhancing effect. However ethanol and polysorbate 80 hardly showed the enhancing effect of OMP. When sodium lauryl sulfate and sodium cholate as enhancer were added in patch, the former case showed higher permeability of OMP.

• YAKHAK HOEJI
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• v.44 no.6
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• pp.595-600
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• 2000

Transdermal delivery of ketorolac tromethamine, a potent non-narcotic analgesic, through human cadaver skin was investigated in vitro. A mixture of ethanol/water (40/60) containing 0, 1, 3, 5, and 8 (w/v)% L-menthol were used as a vehicle and penetration enhancer respectively. The permeation of ketorolac through human cadaver skin from saturated drug solution was evaluated at $37^{\circ}C$ with modified Franz diffusion cell. The in vitro skin flux and lag time were $1.23\;{\pm}\;0.11\;{\mu}g/cm^2{\cdot}hr$ and $5.56\;{\pm}\;0.34\;hr$, respectively. The cumulative amount of penetrated ketorolac containing L-menthol in ethanol/water (40/60) binary system was increased by the following order; 3%, 5%, 8%, 1%, 0%, and the lag time was decresed by the following order; 3%, 5%, 8%, 0%, 1%. The results suggested that a potential use of 3% L-methol is an effective penetration enhancer of ketorolac tromethamine through the human cadaver skin.

• YAKHAK HOEJI
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• v.43 no.4
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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.

• Proceedings of the SCSK Conference
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• 2003.09b
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• pp.464-478
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• 2003

Free radicals and reactive oxygen species (ROS) caused by UV exposure or other environmental facts play critical roles in cellular damage and aging. The extract of tinged autumnal leaves of maple tree(Acer palmatum) has proven to be a powerful antioxidant. The Acer palmatum extract is very effective on the stabilization of biological membranes( containing unsaturated fatty acid). We studied photoprotective effect of the extract against UVB-induced cytotoxicity in human keratinocytes. The extract improved cell viability comparing to control after UVB irradiation. In the determination test of pro inflammatory cytokines the extract decreased expression of interleukin 1 a and 6, which play an important role in inflammation and skin erythema caused by UV. We also studied property of varying cosmetic formulations on the percutaneous absorption of the extract. After 24 hour in vitro penetration study, the content of the extract was more highly detected in skin residue part. This result showed the extract had relatively high compatibility of skin in our emulsion system. On human skin, after appling the product containing the extract we obtained a good result of antiwrinkle effect by skin visiometer. In conclusion, the Acer palmatum extract is a photoprotective and very effective in stressed and aged skin care. And we can predict the extract mainly affects on the skin cell and tissue in our emulsion system.

• 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.

• Archives of Pharmacal Research
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• v.26 no.8
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• pp.644-648
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• 2003

To investigate the feasibility of developing a new ondansetron transdermal system, the effects of vehicles and penetration enhancers on the in vitro permeation of ondansetron hydrochloride (OS) from a pressure-sensitive adhesive (PSA) matrices across dorsal hairless mouse skin were studied. Vehicles employed in this study consisted of various ratios of propylene glycol monocaprylate (PGMC)-diethylene glycol monoethyl ether (DGME) co-solvents and PGMC-propylene glycol (PG) co-solvents with 3% oleic acid. $Duro-Tak^\circledR$ 87-2100 and $Duro-Tak^\circledR$ 87-2196 were used as PSAs. The concentration of DGME in PGMC-DGME co-solvent system affected the release rate; as the concentration of DGME increased, the release rate decreased. The cumulative release amount of OS increased as the ratio of PSA to drug solution decreased. The permeation flux was also primarily affected by the amount of PSAs; as the amount decreased, the permeation flux increased. The overall fluxes from matrix formulations were significantly lower when compared to those obtained from solution formulations. The ratio of PG to PGMC did not affect permeation flux, while the lag time decreased significantly from $5.14\pm3.31 to 0.31\pm0.12$ h as the PG increased from 40% to 60%.

• Journal of Environmental Health Sciences
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• v.42 no.3
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• pp.205-212
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• 2016

Objectives: The objective of this study was to evaluate the distribution of blood lead concentrations of residents in the areas surrounding an industrial complex. Methods: During the three-month period from August to October 2012, informed consent was obtained from a total of 417 residents in Gwangyang and Yeosu. We collected blood samples from all subjects, and their demographic characteristics were acquired using a questionnaire. The blood samples were analyzed using an atomic absorption spectrometer and data analysis was conducted using IBM SPSS version 21.0. Results: The geometric mean concentration of blood lead in all subjects was $1.85{\mu}g/dL$. The highest (p<0.01) blood lead concentrations were in the current drinking group ($2.24{\mu}g/dL$). Blood lead concentrations in the smoking group ($0.59{\mu}g/dL$) were significantly (p<0.05) higher than those in the non-smoking group ($0.24{\mu}g/dL$). Risk assessment was performe using the Korean National Environmental Health Survey (KNEHS) as a reference. The hazard indices of blood lead in males and females were 0.65 and 0.52, respectively Conclusion: We provided baseline data for reference values of toxicity and heavy lead concentrations. Our results might be useful for further evaluation of risks due to exposure to heavy metals via oral, air, and percutaneous routes.

• Journal of Pharmaceutical Investigation
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• v.37 no.3
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• pp.149-158
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• 2007

To investigate the permeability of lidocaine, percutaneous absorption studies were performed using excised hairless mouse skin and the penetration of lidocaine via the skin was determined. To increase the skin permeation of lidocine, the effects of $Labrasol^{(R)}$, $Labrafil^{(R)}$, $Labrafac^{(R)}$ and $Transcutol^{(R)}$ were investigated. The skin permeation of lidocaine was increased when $Labrasol^{(R)}$ and $Transcutol^{(R)}$ were used as permeation enhancer. To evaluate the influence of ultrasound, various factors such as application modes (continuous mode and pulsed mode), frequency (1.0 and 3.0 MHz) and intensity (1.0, 1.5 and 2.0 w/$cm^2$) were investigated with lidocaine hydrogel. The pronounced effect of ultrasound on the skin permeation of lidocaine was observed at all ultrasound energy levels. The influence of frequency having an effect on skin permeation rate was higher in the case of using 1 MHz, 2.0 w/$cm^2$ and continuous treatment. As the intensity of ultrasound increased, the permeation of lidocaine was accelerated. The in vivo anesthetic effects were evaluated by two aspects as mechanical threshold and electrical threshold. Six healthy volunteers consented to the randomized, double-blind, and cross-over designed study in each group. In each subject, 3 groups were adapted such as K group (ultrasound with gel base only), L group (lidocaine gel) and B group (ultrasound with lidocaine gel). In conclusion, lidocaine was potent anesthetic which could be block pain threshold effectively. And ultrasound could accelerate the skin penetration of lidocaine. The phonophoretic delivery system could be a good candidate for lidocaine as a local anaesthetic to improve the skin permeation and in vivo anaesthetic effect.

• KSBB Journal
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• v.31 no.4
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• pp.256-262
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• 2016

The need for natural cosmetic ingredients has been increasing over the world nowadays. Agarose, a natural polymer from red seaweeds, has high hydrophilic character and a function of scaffolder. As skin moisturizer, agarose is adequate for percutaneous absorption. While, blueberry fruits extract possesses rich procyanidins and anthocyanins which show health benefits, anti-oxidant effect, anti-aging and anti-melanogenesis. Stability, sensory preference, skin trouble of the emulsion formula are important for cosmetic product development. In this study, we manufactured an emulsion formula for skin moisturizers using the two ingredients and tested emulsion stability and skin trouble. Total phenolic contents of the blueberry fruits extract were evaluated as well as tyrosinase inhibitory and collagenase inhibitory activities. $IC_{50}$ values of blueberry fruits extract for anti-tyrosinase and anti-collagenase activities were 168 and $112{\mu}g/mL$, respectively using gallic acid as a control ($64.8{\mu}g/mL$). The stability (pH and viscosity) of the formula containing 2% blueberry fruits extracts and 0.1% agarose was measured at five different temperatures (room temp., $25^{\circ}C$, $55^{\circ}C$, $45^{\circ}C$, $55^{\circ}C$) under the sun light at 2 day intervals for 12 days. There has been little pH change at the different temperatures. According to the sensory evaluation, there was no significant flavor, discoloration and physical changes of the formula at $25-65^{\circ}C$. These results suggest that emulsion formula containing blueberry extract and agarose could be used as a candidate for lotion and essence products.

• Journal of Pharmaceutical Investigation
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• v.30 no.4
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• pp.247-252
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• 2000

The advantages of transdermal administration are avoiding hepatic first pass effect, minimizing inter- and intra-patient variation, maintaining steady-state plasma level to provide long-term therapy from a single dose, and allowing a rapid termination of drug input. Clenbuterol, a selective ${\beta}_2-adrenergic$ receptor stimulant, has been introduced as a potent bronchodilator for patients with bronchial asthma, chronic obstructive bronchial disease. For the development of transdermal systems containing clenbuterol, two limiting factors - long lag time and low flux - must be overcome. In this study, we attempted to select optimal formulation for preparation of clenbuterol patch using hairless mouse skin and flow-through diffusion cell. The flux of clenbuterol increased as the percent of clenbuterol dose dependently in the concentration range of 5-15%. Based on this result, we fixed the concentration of clenbuterol as 15%. The effect of various penetration enhancers on percutaneous absorption of clenbuterol through hairless mouse skin was investigated. Labrafil was the most effective enhancer, which increased the permeability of clenbuterol approximately 4-fold compared with the control without penetration enhancer. Optimal enhancer concentration was 3%. The effect of various adhesives on penetration of clenbuterol was also investigated. Among the adhesives studied, MA-31 was the most effective adhesive. Furthermore, the clenbuterol patch composed of 15% clenbuterol, 3% Labrafil and 82% MA-31, which gave most excellent penetration of drug in in vitro penetration study, maintained therapeutic plasma levels in in vivo study using S.D. rats. These studies demonstrated a good feasibility of clenbuterol administration through the intact skin using a transdermal patch, and show a possibility of the development of clenbuterol patches.