• Archives of Pharmacal Research
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• v.27 no.3
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• pp.351-356
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• 2004

A transdermal preparation containing diclofenac diethylammonium (DDA) was developed using an O/W microemulsion system. Of the oils tested, lauryl alcohol was chosen as the oil phase of the microemulsion, as it showed a good solubilizing capacity and excellent skin permeation rate of the drug. Pseudoternary phase diagrams were constructed to obtain the concentration range of oil, surfactant and cosurfactant for microemulsion formation, and the effect of these additives on skin permeation of DDA was evaluated with excised rat skins. The optimum formulation of the microemulsion consisted of 1.16% of DDA, 5% of lauryl alcohol, 60% of water in combination with the 34.54% of Labrasol (surfactant)/ethanol (cosurfactant) (1:2). The efficiency of formulation in the percutaneous absorption of DDA was dependent upon the contents of water and lauryl alcohol as well as Labrasol: ethanol mixing ratio. It was concluded that the percutaneous absorption of DDA from microemulsions was enhanced with increasing the lauryl alcohol and water contents, and with decreasing the Labrasol:ethanol mixing ratio in the formulation.

• Archives of Pharmacal Research
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• v.29 no.5
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• pp.412-417
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• 2006

Triamcinolone acetonide (TA) is a corticosteroid that is used in the systemic and topical treatment of many inflammatory diseases. In this study, a phonophoretic drug delivery system was designed to enhance the TA permeability and the influence of ultrasound was examined. In order to establish the transdermal delivery system for TA, a hydrophilic carbopol gel containing TA was prepared after adopting phonophoresis. A permeation study through mouse skin was performed at $37^{\circ}C$ using a Franz diffusion cell, and the ultrasound treatment was carried out for 10 h. The level of TA permeation through the skin was evaluated under various ultrasound conditions including the frequency (1.0, 3.0 MHz), intensity (1.0, $2.5W/cm^2 $), and duty cycle (continuous, pulse mode) using a 0.5% TA gel. The highest permeation was observed under the ultrasound treatment conditions of low frequency, high intensity, and in continuous mode.

• Journal of the Korean Society for Aeronautical & Space Sciences
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• v.36 no.6
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• pp.587-593
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• 2008

Transdermal and topical drug delivery with minimal tissue damage has been an area of vigorous research for years. Our research team has initiated the development of an effective method for delivering drug particles across the skin (transdermal) for systemic circulation, and to localized (topical) areas. The device consists of a laser ablation based micro-particle acceleration system that can be integrated with endoscopic surgical techniques. We have successfully delivered 3μm size cobalt particles into gelatin models that represent soft tissue with remarkable penetration depth.

• Biomolecules & Therapeutics
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• v.16 no.3
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• pp.226-230
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• 2008

Monoolein-based cubic liquid crystalline systems were formulated for the local delivery of oregonin and hirsutanonol for the treatment of atopic dermatitis. The liquid crystalline phase and its nanodispersion containing drugs were prepared. The skin permeation and deposition properties of the drugs were examined in normal and delipidized rat skin. The proportion of oregonin (%) deposited in normal skin after topical administration of the drugs in the form of aqueous solution, cubic phase or cubic nanodispersions were $1.53\;{\pm}\;0.46$, $3.62\;{\pm}\;0.17$ and $5.13\;{\pm}\;0.73$, and those of hirsutanonol were $2.46\;{\pm}\;0.02$, $5.44\;{\pm}\;0.27$ and $17.28\;{\pm}\;2.19$, respectively. The greater lipophilicity and thus greater skin affinity of hirsutanonol than oregonin contributed the greater amount of skin deposition. The monoolein-based liquid crystalline phases significantly increased the amount of both drugs permeated and deposited. Approximately 3.2, 2.1 and 3.0 times greater amount of oregonin, and 3.4, 2.1 and 2.2 times greater amount of hirsutanonol were deposited in delipidized skin after administration of each drug in the form of aqueous solution, cubic phase and cubic nanodispersions system, respectively, because of lowered barrier function of the delipidized skin. In this study, the effects of drug property, vehicles type and skin condition on skin deposition and permeation properties of drug were examined and concluded that monoolein-based liquid crystalline systems would be a promising formulation for the local delivery of drugs.

• Journal of Pharmaceutical Investigation
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• v.28 no.2
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• pp.87-92
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• 1998

Kojic acid (KA) is an antimelanogenic agent which has been widely used in cosmetics to whiten the skin color. However, it has the drawbacks of the skin irritancy and the instability against the pH, temperature, and light. In order to overcome these problems, various topical gels and multiple emulsion creams which can control the release of active ingredient, KA, were formulated employing cream bases of mineral oil with caprylic capric triglyceride and hydrophilic polymers such as chitosan, carbopol. and pluronics. Using Franz diffusion cells mounted with a synthetic cellulose membrane (MWCO 12,000), drug release characteristics of the formulations were evaluated by the HPLC assay of KA concentration in the receptor compartment of pH 7.4 phosphate buffered saline solution. Drug release from chitosan-based gels (ChitoGel) obeyed to the first order kinetics with a rapid release especially in the initial period. However, pluronic-based gels (PluGel) and carbopol-based gels (CarboGel) revealed controlled release of drug to some extent, followed by the square root-time kinetics. Moreover, the release of KA was further controlled with the W/O/W multiple emulsion creams (MultiCream), showing the apparent zero order release kinetics by virtue of dynamic ratecontrolling membrane of the oil layer. The flux $(J,\;{\mu}g/cm^2/hr)$ of ChitoGel. CarboGel. PluGel. and MultiCream in the initial period of 6hr were 73.30, 28.67. 24.04 and 7.72, respectively. On the other hand, the skin irritancy score of ChitoGel and MultiCream were observed as 2.5 and 2.3 respectively, in the rabbit skin irritation test. Although there were insignificant differences at p<0.05 between those formulations, it was possible to conclude that the W/O/W multiple emulsion creams containing KA might be a good candidate for an antimelanogenic drug delivery system due to the controlled release of acidic drug molecules.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.247.2-247.2
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• 2003

To increase skin permeability of LMWH (Low Molecular Weight Heparin), ultradeformable liposomes were developed. Ultradeformable liposomes were developed by Egg phosphatidylcholine (Egg-PC) and edge activator. Entrapment efficiency, vesicle size and zeta potential of vesicles were determined and characterized for deformability and stability. Transepidermal permeation of LMWH was compared to saturated aqueous control in vitro. The steady-state flux and its maximum time were calculated from the flux curves. (omitted)

• Journal of Pharmaceutical Investigation
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• v.38 no.2
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• pp.87-92
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• 2008

Wood vinegar is well known as a softening agent affecting on the stratum corneum that is easy to penetrate into the skin. In this study, we prepared mixed ursolic acid hydrogel with wood vinegar(1, 2, 5%) as a penetration enhancer. The accumulation of ursolic acid in the skin from hydrogels was evaluated in vitro hairless mouse skin and skin moisturizing effect of them was evaluated using the corneometer and the tewermeter. And the role of stratum corneum as a protective barrier was evaluated as well. The hydrogels were retained about 40% of water retention capacity 2hrs and had better effect on the stripped skin than full-thickness skin. The accumulation of ursolic acid through stripped skin from hydrogels with wood vinegar was not change compared to normal skin, which indicated the action site of wood vinegar and the accumulation site of ursolic acid would be stratum corneum. From these result, we could find wood vinegar seems to be a good enhancer for active materials with anti-wrinkle and anti aging effect such as ursolic acid, and can be a developed topical delivery system maintaining excellent water retention capacity.

• Archives of Pharmacal Research
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• v.29 no.12
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• pp.1187-1192
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• 2006

The aims of this study were to encapsulate arbutin (AR) in liposome to enhance the skin-whitening activity, and to investigate the effect of liposome formulation on the entrapment efficiency (EE%), skin permeation rate and skin deposition. The liposomes were prepared by a film dispersion method with several different formulations and were separated from the solution by using the gel-filtration method. The physical (size distribution, morphology) and chemical (drug entrapment efficiency, hairless mouse skin permeation and deposition) properties of liposomes were characterized. The entrapment efficiency in all liposome formulations varied between 4.35% and 17.63%, and was dependent on the lipid content. The particle sizes of liposomes were in the range of $179.9{\sim}212.8\;nm$ in all liposome formulations. Although the permeation rate of AR in the liposome formulations decreased compared with AR solution, the deposition amount of AR in the epidermis/dermis layers increased in AR liposomal formulation. These results suggest that liposomal formulation could enhance the skin deposition of hydrophilic skin-whitening agents, thereby enhancing their activities.

• Journal of Pharmaceutical Investigation
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• v.36 no.5
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• pp.305-308
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• 2006

Poloxamer-based hydrogel formulation for the topical delivery of ascorbic acid(AsA) was prepared and the effect of limonene on AsA skin permeation and localization was evaluated. In vitro rat skin permeation study, the AsA skin permeation of limonene-containing hydrogel was about 3 to 5 fold higher than control hydrogel. However the amount of permeated AsA was independent to the concentration of limonene. On the other hand the localized amount of AsA after 2 h increased proportion to the content of limonene. The increase in the ratio of localized AsA($Q_L$) to permeated AsA($Q_P$) was attributed to the limonene's ability of making polar pathway within stratum corneum by interacting on lipid domain of the skin and the AsA's hydration effect on the stratum corneum and effect on the protein domain of the skin.

• Journal of Pharmaceutical Investigation
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• v.39 no.6
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• pp.437-443
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• 2009

To develop a topical bioadhesive formulation of clotrimazole for enhanced transdermal delivery, hydroxypropyl methylcellulose gel containing permeation enhancer was formulated and permeation studies were carried out. The release characteristics of the drug from the gel formulation were examined according to the receptor medium, drug concentration, and temperature. The rate of drug release from the gel increased with increasing drug concentration and temperature. The activation energy (Ea) of drug permeation, which was calculated from the slope of log P versus 1/T plots, was 14.41kcal/mol for a 1%(w/w) loading dose. The enhancer, such as saturated, unsaturated fatty acids, pyrrolidones, propylene glycol derivatives, glycerides, and non-ionic surfactants, were incorporated onto the gels to increase the amount of drug permeation into the skin. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the highest level of enhancement. These results show that clotrimazole gels containing polyoxyethylene 2-oleyl ether could be used for the enhanced transdermal delivery of clotrimazole.