• Archives of Pharmacal Research
• /
• v.18 no.4
• /
• pp.224-230
• /
• 1995

Recently, many attempts have been made to use hydrogels of various polymers as delivery systems of various drugs and bioactive materials to prolong and control their phamacological activities. In this study, we have evaluated the physico-chemical properties of methacrylic acid-methyacrylic acid methyl ester copolymer 9Eudispert mv)m a acrylic resin hydorgel, and its application to transdermal delivery system. In the dissolution tests, the release rate of salicylic acid (SA) and sodium salicylate (SOd. SA) were faster than lidocain (LD) and lidocain-HCl(LD-HCl). As the concentration of Eudispert mv polymer increased, the extensibility of Eudispert mu hydrogel decreased, whereas the swelling ratio increased. The more NaOH and polymer concentration increased, the more osmotic pressure linearly increased. The skin permeation of Sod. SA, an acidic model drug, was remarkably enhanced by Eudispert mv hydrogel. All fatty acids, except for Sod. glycolate, dramatically increased the skin permeation flux in Eudispert mu hydrogel containing LD-Hcl, a basic model drug. Consequently, it is suggested that Eudispert mv hydrogel may be used as potential transdermal delivery vehicle.

• Archives of Pharmacal Research
• /
• v.29 no.5
• /
• pp.412-417
• /
• 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 Pharmaceutical Investigation
• /
• v.28 no.1
• /
• pp.43-50
• /
• 1998

Niosomes are vesicles formed from synthetic non-ionic surfactants, offering an alternative to chemically unstable and expensive liposomes as a drug carrier. Non-ionic surfactant and cholesterol mixture film leads to the formation of vesicular system by hydration with sonication method. The formation of niosome was ascertained by negative staining of TEM. The entrapment efficiency of niosomal suspension was gradually increased with increasing the ratio of cholesterol to surfactant. It was found that the niosome with 6 : 4 (polyoxyethylene 2-cetyl ether: cholesterol) ratio was more stable than those with other ratios. The topical application of acyclovir(ACV) in the treatment of herpes simplex virus type 1(HSV-1) skin disease has a long history. There are an increasing number of reports, however, in which topical ACV therapy is not as effective as oral administration. Lack of efficacy with topical ACV has been hypothesized to reflect the inadequate delivery of drug to the skin. We investigated the permeation of niosome containing $[^{3}H]ACV$ in hairless mouse skin using Franz diffusion cell model. Permeation coefficient(P) of aqueous ACV was $6.7{\times}10^{-4}\;(cm/hr)$ and that of ACV in niosome was $23.4{\times}10^{-4}\;(cm/hr)$, suggesting about 3.5 times increase in the transdermal permeation.

• Journal of Pharmaceutical Investigation
• /
• v.30 no.4
• /
• pp.283-288
• /
• 2000

The purpose of the present study was to investigate the topical bioavailability of retinol (vitamin A) after its transdermal administration. For this purpose, we developed the convenient HPLC method to measure the retinol concentration in the biological fluids such as plasma and skin tissues. The low detection limit was $0.1\;{\mu}g/ml$ using a gradient HPLC system of UV detection. The initial plasma concentration of retinol was about $20\;{\mu}g/ml$ after its i.v. bolus administration (4.32 mg/kg). The half life $(t_{1/2{\alpha}})$ in the distributive phase was 1.3 min, while retinol was slowly disappeared in the post-distributive phase. On the other hand, the maximum plasma concentration $(C_{max})$ was about 776 ng/ml after appling to rat skin at a dose of 43.2 mg/kg. Furthermore, the concentration of retinol in the skin tissues was about 600 ng/g tissue at 12 hr after its transdermal administration. In conclusion, the initial plasma concentration of retinol was comparable with the skin concentration after its cutaneous absorption, followed by being decreased with the passage of the time.

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

• Journal of Pharmaceutical Investigation
• /
• v.27 no.4
• /
• pp.303-311
• /
• 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
• /
• v.29 no.1
• /
• pp.29-36
• /
• 1999

Aceclofenac is an non-steroidal antiinflammatory drug which has been used in the treatment of rheumatoidal rthritis and osteo-arthritis. In order to decrease the gastric ulcerogenic effects and contol the plasma level of aceclofenac, we have developed the transdermal delivery system of aceclofenac plaster, which were formulated employing matrix polymers of acrylates and penetration-enhancers such as $Lauroglycol^{\circledR}$, $Transcutol^{\circledR}$, oleic acid and linoleic acid. Using Franz diffusion cells mounted with a rat skin, transdermal penetration characteristics of the formulations were evaluated by the HPLC assay of aceclofenac and diclofenac, an active metabolite, in the receptor compartment of pH 7.2 phosphate buffered solution. Skin penetration was increased when the content of aceclofenac increased, showing the flux $(J,\;{\mu}g/cm^2/hr)$ of 0.37 and 2.50 for 2% and 6.75% of the content, respectively. The flux$(J,\;{\mu}g/cm^2/hr)$ from plasters made of $Durotak^{\circledR}$ 87-2074, $Durotak^{\circledR}$ 87-2510 and $Durotak^{\circledR}$ 87-2097 were 2.50, 2.77 and 4.39, respectively. $Durotak^{\circledR}$ 87-2074 showed the lowest penetration due to the carboxylic acid group in the polymer, which might form a strong hydrogen bonding with a secondary amine of aceclofenac. Although both $Durotak^{\circledR}$ 87-2510 and $Durotak^{\circledR}$ 87-2097 are amine-resistant adhesives, $Durotak^{\circledR}$ 872510 showed lower penetration than $Durotak^{\circledR}$ 87-2097 because of the hydroxyl group in $Durotak^{\circledR}$ 87-2510, which might form a weak hydrogen bonding with aceclofenac. These results reveal that the functional group in acrylic polymers would greatly affect the release of aceclofenac from the matrix, which is the rate-limiting step in the penetration of aceclofenac through rat skins. The penetration of aceclofenac from plasters using different penetration-enhancers increased in the following order: Transcutol < linoleic acid < oleic acid. And the flux from the plasters containing oleic acid as a penetrationenhancer was 2.22 times greater than that of creams, which suggest that a newly deveolped aceclofenac plaster could be used in the treatment of rheumatoidal arthritis and osteo-arthritis as an advanced transdermal delivery system.

• 한국생물공학회:학술대회논문집
• /
• 2003.10a
• /
• pp.72-72
• /
• 2003

• Proceedings of the PSK Conference
• /
• 2001.04a
• /
• pp.228.1-228.1
• /
• 2001

• Journal of Pharmaceutical Investigation
• /
• v.24 no.1
• /
• pp.11-16
• /
• 1994

In order to reduce the systemic side effects and gastrointestinal irritation of ketoprofen after its oral administration, it was formulated as a 3% ketoprofen gel (ID-GEL) with Pluronic F-127. The pharmacokinetic characteristics of ID-GEL was evaluated following its transdermal application on the dorsal skin of rats at the dose of 9 mg/kg in reference to those of existing 3% ketoprofen gels. Even though the maximum concentration of 810 ng/ml was reached at 6 hrs postdose, the plasma concentration was kept almost constant until 24 hrs postdose, which suggested that ketoprofen was released continuously from the gel during this period. The bioavailability of ID-GEL was two times higher than those of existing 3% ketoprofen gels, based on the calculated area under the plasma concentration-time curves after the percutaneous administration.