• Journal of Pharmaceutical Investigation
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• v.32 no.2
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• pp.87-93
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• 2002

This study is to enhance drug penetration via skin and investigate anti-inflammation effect following adoption of ultrasound. For this goal gel containing triamcinolone was prepared and the skin penetration rate and the change effects of blood plasma ingredients and serum enzyme were investigated. Using Franz type diffusion cell and the skin of hairless mouse, the permeation enhancing effect of ultrasound was tested. After the injury by direct trauma, the blood test was performed by measuring WBC, lymphocyte, and neutrophyl, and by analyzing CPK and LDH. The ultrasound transducer whose technical specification is geometric area(GA) $1.4\;cm^2$, effective radiation area(ERA) $0.8\;cm^2$, and beam non-uniformity ratio(BNR) 6.0 max was used. The influence of frequency having an effect on skin permeation rate was higher in the case of using 1MHz and continuous treatment. The temperature of receptor phase was not influenced in skin permeation by phonophoresis. Skin permeation increase attended by intensity of ultrasound, the permeation of triamcinolone was accelerated at $2.5\;w/cm^2\;than\;1.0\;w/cm^2$. Following muscle injury phonophoretic group the number of WBC, neutrophil and lympholyte were decreased significantly as compared with both control group and ultrasound group. The result of variation of serum CPK and LDH activity conformed to the phonophoretic effect as same pattern with the variation of WBC, neutrophil and lymphocyte.

• 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.

• YAKHAK HOEJI
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• v.60 no.1
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• pp.36-45
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• 2016

This study was aimed to enhance the percutaneous absorption of tizanidine hydrochloride (TZ) across Strat-M$^{TM}$ artificial membrane and excised hairless mouse skin using various vehicles and chemical permeation enhancers. Solubility studies were performed using hydrophilic and lipophilic vehicles. To initially evaluate vehicle effects on skin permeation, Strat-M$^{TM}$ membrane was adopted using Franz-type diffusion cells loaded with 0.4 mg donor dose. Effects of fatty acids on the permeation of TZ from PG and PGMC were compared, and the effects of various hydrophilic vehicles in the presence of linoleic acid were studied using excised hairless mouse skin specimens. The mean solubility (mg/ml) of TZ in hydrophilic vehicles was higher: water > PG > DMSO > ethanol > PEG 200 > NMP > PEG 300 > PEG 400 > DGME, and solubilities in lipophilic vehicles such as PGMC, PGMC, IPM, Captex 200 and Captex 300 were much less than 1.0 mg/ml. Permeation rates through StratTM membrane from pure vehicles were in the rank order: PGMC ${\geq}$ LBF > DMSO ${\geq}$ NMP ${\geq}$ PGML ${\geq}$ PG ${\geq}$ PEG 200 ${\geq}$ DGME ${\geq}$ EtOH. However, permeation rates of TZ through hairless mouse skin from pure vehicles were very low, although PG showed the highest flux ($1.66{\pm}0.28{\mu}g/cm^2{\cdot}hr$). Therefore, PG was selected in further studies. Addition of enhancers (3 v/v%) into PG markedly increased the flux (${\mu}g/cm^2{\cdot}hr$): oleyl alcohol ($14.9{\pm}3.1$) ${\geq}$ oleic acid ($14.5{\pm}1.6$) ${\geq}$ linoleic acid ($13.7{\pm}1.3$) > capric acid ($4.4{\pm}0.6$) > caprylic acid ($2.1{\pm}0.4$). Among hydrophilic vehicles with linoleic acid, PG and DMSO revealed relatively higher permeation for TZ. Increase of donor dose in PG resulted in dose-dependent permeation fluxes. These results suggest that permeation properties of TZ from nonaqueous solutions are markedly different between Strat-$M^{TM}$ membrane and excised hairless mouse skin, and transdermal delivery of TZ would be feasible with a combination of PG and enhancers.

• 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.30 no.1
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• pp.27-32
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• 2000

Various release test methods have been applied for the evaluation of nicotine release in vitro from commercial patches. However, whether and how the release data reflect the permeation of nicotine across the skin, is not fully elucidated. To predict in vivo bioavailability from in vitro release tests, correlation between in vitro release and in vitro skin permeation was assessed in the present study. Release of nicotine from three commercial patches was measured for 24 hours under nine experimental conditions which were classified depending on the apparatus (i.e., paddle over disk, cylinder and reciprocating holder) and dissolution media (i.e., phosphate buffer pH 7.4, water and the 1 % phosphoric acid pH 1.5). In vitro permeation of nicotine from the patches across the human cadaver skin was also measured using a diffusion cell. The release of nicotine was better explained by the Higuchi's equation rather than by the first order rate equation. Correlation between the release rate and the in vitro skin permeation differed among the patches. However, in general, the cylinder method, in which water is used as a dissolution medium, showed the highest correlation among the nine release test conditions.

• Journal of Pharmaceutical Investigation
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• v.37 no.3
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• pp.167-171
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• 2007

Itraconazole is one of the most potent antifungal agents available in the market today. However, the low bioavailability due to its poor-water solubility calls for an alternative formulation to the current oral type. A topical itra-conazole-containing formulation may be of use for several reasons including the opportunity to reduce adverse events and generate high local tissue levels, more rapid drug delivery, and lower systemic exposure. The purpose of the present study was to investigate the vehicles for topical skin delivery of itraconazole. The effect of formulations on the hairless mouse skin permeation and deposition of itraconazole was determined using Franz diffusion cells at $37^{\circ}C$. Benzyl alcohol in micro-emulsion significantly increased the solubility of itraconazole, thereby increasing the skin permeation rate. However, lipo-some formulation showed the lowest solubility and permeation rate of itraconazole. Although the solubility of itraconazole in hydrogel formulation was lower than that in microemulsion, skin permeation rate was significantly higher probably due to its adhesive property. Therefore, microemulsion-based hydrogel formulation is expected to synergistically increase the skin permeation rate and skin deposition of itraconazole.

• YAKHAK HOEJI
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• v.42 no.1
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• pp.39-45
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• 1998

Kojic acid, antimelanogenic agent, has been widely used in cosmetics to lighten the skin color. However, it has skin irritancy and instability against pH, temperature and light. To overcome these problems and optimize the molecular structure of kojic acid (KA), a prodrug, kojic acid monostearate(KMS), has been synthesized to modify the topical drug delivery in the point of sustained release of the parent drug via enzymatic hydrolysis during skin absorption. The prodrug was tested for enzymatic hydrolysis with cytosolic fraction of hairless mouse, skin. From the in vitro skin permeation study through hairless mouse skin, we found that KMS was retained in the skin and generated KA continuously by the skin esterase cleavage. In addition, topical formulations of o/w type creams and polyolprepolymer-containing cream were further tested for whitening effects using in vivo yellow skin guinea pig model.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.24 no.3
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• pp.38-44
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• 1998

The skin permeation and the skin primary irritation of two UV filters from caprylic capryl triglyceride (oil), oil in water (O/W) and water in oil (W/O) emulsions, were evaluated. We selected octyl moth-oxycinnamate (OMC) broadly used in cosmetics and polymeric sunscreen agent (PSA, average MW: 2,000) synthesized by the coupling reaction of 2-ethylhexyl 4-hydroxycinnamate with poly vinylbenzyl chloride, as model UV filters. For in vitro skin permeation experiments, Franz diffusion cells (effective diffusion area:1.766cm) and the excised skin of female hairless mouse aged 8 weeks were used. Oil or emulsion containing UV filters was applied in the donor compartment. The skin primary irritation was evaluated with fe-male guinea pigs (8-10 weeks,350-400 g). In oil and emulsions, the skin permeability and the skin primary irritation of PSA were lower than those of OMC. The skin permeability of UV filters was lower when they were in oil-in-water emulsion (OIW) than water-in-oil emulsion (W/O). We suggest that O/W system would be more useful when compared with W/O system, and PSA could be a good candidate for a future sunscreen agent for reducing the skin irritation.

• KSBB Journal
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• v.26 no.6
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• pp.505-512
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• 2011

Psolarea corylifolia extract that contains bakuchiol is known to have anti-microbial, anti-inflammatory and anti-scarring effects. In this study, a vesicles such as liposome, niosome, and transfersome were produced to encapsulate P. corylifolia extract and measured their stability and physiochemical property. The skin permeation and partitioning of P. corylifolia extract in the vesicles were elucidated in nude mouse skin by using Franz diffusion cells after topical application for 24 h. After storage at 25, 40, $70^{\circ}C$, and light, the stability of bakuchiol incorporated into the vesicles was maintained for 30 days. The optimal concentration of P. corylifolia extract entrapped into the vesicles was found to be 5~10%. From the physicochemical studies, after storage at 4, 25, and $40^{\circ}C$, the viscosity and particle size of the vesicles remained in 30~80 cP and the nanosize range for 6 months, respectively. From the permeation experiments, niosome showed a higher amount of bakuchiol permeated through the mouse skin compared to liposome and transfersome after 24 h. From these results, niosome and transfersome could be a good bioavailability enhancement system (BAES) for P. corylifolia extract to improve the skin permeation and stability.

• Archives of Pharmacal Research
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• v.28 no.2
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• pp.243-248
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• 2005

To improve the skin permeability of piroxicam, a new oil-in-water microemulsion containing $0.5\%$ piroxicam was developed. Among various oils investigated for their suitability as an oil phase for the microemulsion system, oleic acid showed both excellent solubility and skin permeation enhancing effect for piroxicam. Microemulsion existence ranges were identified through the construction of the pseudo-ternary phase diagram. The effect of the content of oleic acid and the ratio of the surfactant/cosurfactant on skin permeation of piroxicam were evaluated with excised rat skins. The optimum formulation with the highest skin permeation rate ($47.14\;{\mu}g/cm^2/h$) consisted of $0.5\%$ piroxicam, $10\%$ oleic acid, $60\%$ Labrasol/ethanol (1:5) and water.