• 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.

• Journal of Pharmaceutical Investigation
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• v.23 no.3
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• pp.1-8
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• 1993

A simple and quick method based on the transient diffusion theory for predicting the steady state rate of penetration of a drug after transdermal drug administration was proposed. The amount of drug entering the stratum corneum was determined by 20 strippings with an adhesive tape. From the profile of the amount of drug as a function of the number of strippings, the quantity of drug on the surface of stratum corneum was extrapolated. Based on the amounts of drug entering the stratum corneum during two time intervals $(t_1\;and\;t_2)$ within 1 hour after the application, the diffusion and partition coefficient were determined. Once the diffusion coefficient of the drug in the stratum corneum and the partition coefficient (stratum corneum/vehicle) were determined from the present approach, the steady-state flux of penetration across the stratum corneum was calculated. The steady-state rates of penetration of ascorbic acid and estradiol across hairless mouse skin were evaluated from this approach and compared with those obtained from ill vitro penetration experiment using excised hairless mouse skin. The data confirmed that the proposed method can predict the steady-state rate of penetration of these drugs across the stratum corneum.

• Journal of Pharmaceutical Investigation
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• v.31 no.3
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• pp.181-184
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• 2001

The purpose of this study was to develop transdermal drug delivery system (TDDS) for the combination of physostigmine and procyclidine. The effects of various pressure sensitive adhesives (PSA) on the percutaneous absorption of procyclidine across hairless mouse skin were evaluated to select an appropriate PSA. In addition, the influences of various vehicles on the percutaneous absorption of procyclidine from PSA matrix across hairless mouse skin were evaluated using flow-through diffusion cell system at $37^{\circ}C$. Physostigmine did not have any influence on the permeation rate of procyclidine. The flux of procyclidine was the highest in silicone and PIB and was relatively lower in SIS, Acryl, and SBS adhesive matrices, however, their use was limited by the crystallization of the drug in the matrix. Among acrylic adhesives, the permeability of procyclidine was the highest from poly (ethylene oxide) grafted acrylic adhesive. Some enhancers show different enhancing effect depending on the drug, however, many of the tested enhancers showed enhancing effect for the permeation of both procyclidine and physostigmine to some extent. $Crovol^{\circledR}$ EP 40 showed the highest enhancing effect on the permeation of both compounds. The size of TDDS to provide required permeation rate was estimated to be $35\;cm^2$ based on available information.

• Journal of Pharmaceutical Investigation
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• v.35 no.1
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• pp.7-16
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• 2005

Gardeniae Fructus is consisted of geniposide and it's derivatives. For the purpose of treatment of skin disease, geniposide and hydrolyzed products (HP) of Gardeniae Fructus were studied on skin permeation and cross1inking with biological tissue. The hydrolyzed products (HP) and active ingredients of Gardeniae Fructus were identified and investigated about skin permeability. Genipin has provided low cytotoxic cross1inking reagents and formed stable and biocompatible crosslinked products. The permeation enhancing effects of geniposide and genipin under the hydrolyzed products of cream and hydrogel preparations were tested using Franz type diffusion cell and the skin of hairless mouse. The remaining proportions of geniposide and genipin were measured in the hydrolyzed products of cream and hydrogel preparations. The crosslinking of epidermic and endodermic tissue with genipin under the hydrolyzed prodcuts of cream and hydrogel preparation was observed using light microscopy. Increased absorption ratio of the skin of hairless mouse about genipin was higher than that of geniposide. Loads at break, tensile strengths and skin permeation rate of the hydrolyzed products (HP) of cream and hydrogel preparations were higher than the nonhydrolyzed products (NHP). The hydrolyzed products (HP) of cream and hydrogel of Gardeniae Fructus Extracts were proper preparations and crosslinking agents to increase the transdermal absorption with epidermic and endodermic tissue.

• 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.29 no.4
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• pp.343-348
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• 1999

The purpose of this study is to prepare the controlled release adhesive patch containing naproxen. Pressuresensitive adhesive (PSA)-type patch was fabricated by casting of polyisobutylene (PIE.) and mineral oil in toluene. Membrane-controlled release (MCR)-type patch was prepared by the attachment of the controlled release membrane on the PSAtype patch. The membrane was mainly composed of Eudragit, polyethylene glycol(PEG) and glycerin. The drug release profile and skin permeation test with various patches were evaluated in vitro. The release of naproxen from PIE-based PSAtype patch with various loading doses fitted Higuchi's diffusion equation. However, the permeation of naproxen through hairless mouse skin from PSA-type patch followed zero-order kinetics. In MCR-type patch, thickness of controlled release membrane affected on the drug release rate highly. In the composition of membrane, the release rate was decreased as the ratio of Eudragit increased. The drug release from the MCR-type patch followed zero order kinetics. The permeation of naproxen through hairless mouse skin from MCR-type patch showed lag time for the intial release period and didn't fit the zero-order kinetics

• Toxicological Research
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• v.30 no.4
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• pp.283-289
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• 2014

Tea flavonoids and polyphenols are well known for their extraordinary antioxidant activity which is considered important for anti-aging processes in animals. This study evaluated the anti-wrinkle effects of three different kinds of tea (Camellia sinensis) water extracts (CSWEs) including green, white, and black teas using a photoaged hairless mouse model. Data showed that the CSWE-treatment greatly improved skin conditions of mice suffering from UVB-induced photoaging, based on the parameters including the skin erythema index, moisture capacity, and transepidermal water loss. In addition, the wrinkle measurement and image analysis of skin replicas indicated that CSWEs remarkably inhibited wrinkle formation. In histological examination, the CSWE-treated mice exhibited diminished epidermal thickness and increased collagen and elastic fiber content, key signatures for skin restoration. Furthermore, the reduced expression of MMP-3, a collagen-degradative enzyme, was observed in the skin of CSWE-treated animals. Interestingly, comparative data between green, white, and black tea indicated that the anti-wrinkle activity of white tea and black tea is equally greater than that of green tea. Taken together, these data clearly demonstrated that CSWEs could be used as an effective anti-wrinkle agent in photoaged animal skin, implying their extended uses in therapeutics.

• Archives of Pharmacal Research
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• v.24 no.6
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• pp.578-583
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• 2001

To investigate the feasibility of developing a new tenoxicam plaster, the effects of vehicles and penetration enhancers on the in vitro permeation of tenoxicam from a pressure-sensititre adhesive (PSA) matrices across the dorsal hairless mouse skin were studied. Vehicles employed in this study were propylene glycol (PC)-oleyl alcohol (OAI), PG-oleic acid (OA), and diethylene glycol monoethyl ether (DCMI)-propylene glycol monolaurate (PCML) cosolvents with/without fatty acids. In this studys amines such as triethanolamine (TEA) and tromethamine (TM) were additionally used as a solubilized. Among PSAs used, $Duro-Tak^{\circledR}$87-2510 showed much higher release rate than either $Duro-Tak^{\circledR}$ 87-2100 or $Duro-Tak^{\circledR}$87-2196. The relatively high flux rate was obtained with the formulation of DCMI-PCML (40:60, v/v) with 3% OA and 5% TM, and the flux increased as a function of the dose;the initial flux up to 12 h was $4.98{\pm}1.38{\;}{\mu\textrm{g}}/{\textrm{cm}^2}/h$ at the tenoxicam dose of $50{\;} mg/70{\;}{\textrm{cm}^2}$. This flux was much higher than that of a commercial piroxicam patch ($Trast^{\circledR}$) ($1.24{\pm}0.73{\;}{\mu\textrm{g}}/$\textrm{cm}^2/hr$) with almost only one-third that of the commercial patch. Therefore, these observations indicated that these composition of tenoxicam plaster may be practically applicable.

• 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%.