• Journal of Pharmaceutical Investigation
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• 제40권3호
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• pp.167-173
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• 2010

Repeated oral administration of hydrochlorothiazide, a loop diuretic, due to transient high blood levels, may cause adverse effects such as gastric disturbance, nausea, high blood sugar, and hyper lipidemia. Transdermal administration could avoid some of these systemic side effects and gastric disorders. We have developed a matrix using ethylene-vinyl acetate (EVA), a heat-processible and flexible material, for transdermal delivery of hydrochlorothiazide. Drug solubility was highest at 40% PEG-400 volume fraction. Drug release increased as concentration increased with a linear relationship between the release rate and the square root of loading dose. Increasing temperature increased drug release from the EVA matrix. The activation energy, measured from the slope of log P versus 1000/T, was 11.9 kcal/mol for a 2.5% loading dose from EVA matrix. Diethyl phthalate had the highest plasticizing effects on the release of hydrochlorothiazide. To increase the skin permeation of hydrochlorothiazide from the EVA matrix, enhancers such as the saturated fatty acids, the unsaturated fatty acids, and the non-ionic surfactants were added to the EVA matrix, and skin permeation was evaluated using a modified Keshary-Chien diffusion cell fitted with intact excised rat skin. Polyoxyethylene 23-lauryl ether showed the highest enhancing effects. In conclusion, transdermal delivery of hydrochlorothiazide could be improved from an EVA matrix containing plasticizer and permeation enhancer.

• Journal of Pharmaceutical Investigation
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• 제30권4호
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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.

• The Korean Journal of Pain
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• 제9권1호
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• pp.178-182
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• 1996

Background: To evaluate the effect of prophylactic transdermal scopolamine in reducing nausea associated with postoperative epidural morphine. Methods: 30 healthy patients scheduled for cesarean section were given local anesthetics epidurally for surgical anesthesia. After delivery of the baby, transdermal scopolamine patch($Kimite^{(R)}$ Myung Moon Pharm. Co., Seoul, Korea) was applied to the study group(n=15) and placebo patch to the control group(n=15). Postoperative analgesia was provided soley with epidural morphine. Nausea was treated with metoclopramide. Results: During 24 hours postoperatively, the mean nausea score was significantly lower in the study group than in the control group. But the nausea incidence was not significantly different between the two groups. The mean number of times antiemetic drugs which were administered to patients were lower in the study group than in the control group($1.5{\pm}0.5$ vs $3.3{\pm}1.3$, p<0.05). Conclusion: Transdermal scopolamine patch provides antiemetic effect simply, continuously and safely, preventing nausea which could occur during administration of epidural morphine after cesarean section.

• 약학회지
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• 제47권2호
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• pp.120-124
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• 2003

Due to its profound intestinal first-pass metabolism, oral eperisone hydrochloride produces a very low bioavailability and a very short muscle relaxant activity. To improve the efficacy and compliance of eperisone, we designed a new dosage form, the transdermal patch and evaluated the muscle relaxant effects of this patch in rats. The muscle relaxant activity was assessed by measurement of forelimb grip strength and hanging test in rats. The transdermal patch of eperisone hydrochloride showed significant muscle relaxant activity at 0.5, 1.5 and 3 cm$^2$/200 g rat (1.39, 4.17 and 8.33 mg of eperisone hydrochloride/kg, respectively) in a dose-dependent manner and the effects were lasted over 24 hours. The oral eperisone hydrochloride showed significant activity at 12.5, 25 and 50 mg/kg in a dose-dependent manner but the activity was within 1 or 2 hours after administration. These results suggest that the eperisone hydrochloride is absorbed efficiently from transdermal patch and the patch can exert potent and long-lasting muscle relaxant activity. This transdermal patch will increase the efficacy and compliance in the clinical use of eperisone hydrochloride.

• 대한임상독성학회지
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• 제11권1호
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• pp.49-52
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• 2013

Fentanyl, a synthetic, highly selective opioid ${\mu}$-receptor agonist, is 50 to 100 times more potent than morphine. The low molecular weight, high potency, great transdermal permeation rate and lipid solubility of fentanyl make it very suitable for transdermal administration. Durogesic is a novel matrix transdermal system providing continuous systemic delivery of fentanyl. In recently, there are many reports that misused or overused fentanyl transdermal patches result in severe intoxication of fentanyl. We present a case of fentanyl toxicity with misused durogesic transdermal patch and discuss the safe and appropriate application of the patches. In conclusion, fentanyl patches should be used in opioid tolerant patients and prescribed at the lowest possible dose and titrated upward as needed. All patients and their caregivers should be educated safe application of fentanyl patches and advised to avoid exposing the patches application site to direct external heat sources, such as heating pads, or electric blankets, heat lamps, sauna, hot tubs, and others. In addition, concomittant medications that affect fentanyl's metabolism should be avoided.

• Journal of Pharmaceutical Investigation
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• 제24권1호
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• pp.17-24
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• 1994

The antiinflammatory and antirheumatic activities of a 3% ketoprofen gel (ID-GEL) were evaluated using carrageenan-induced paw edema method and adjuvant-induced arthritis method, respectively, after its transdermal administration of 50 mg on rat paws in reference to existing transdermal preparations containing 3% ketoprofen and other nonsteroidal antiinflammatory drugs (NSAIDs). The % inhibition of carrageenan-induced edema by ID-GEL was 56.2-65.0%, close to the maximum inhibition obtainable with this model, while the % inhibition by existing 3% ketoprofen gels and other NSAID transdermal preparations were 33.8-47.7% and 18.7-29.2%, respectively. ID-GEL had a pronounced antirheumatic activity in both preventive and curative studies with adjuvant-induced arthritis in rats in respect with the inhibition of edema, arthritis score and weight gain, in reference to existing 3% ketoprofen gel.

• 한국응용과학기술학회지
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• 제33권4호
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• pp.667-675
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• 2016

Nanoemulsions are actively used in several applications for pharmaceutical, cosmetic and chemical industries. In this study, we propose the use of microfluidizer known as high pressure homogenizer to prepare lipid nanoemulsion as a potent cosmetic delivery carrier. The lipid nanoemulsions were prepared by O/W emulsion with hydrogenated lecithin and different type of oils. Effects of oil type on the stability of the lipid nanoemulsion were investigated with Dynamic Light Scattering (DLS) and Zeta-potential. Arbutin was used as model drug for transdermal administration through hairless mouse skin. Transdermal arbutin delivery using the lipid nanoemulsions was studied with HPLC method.

• Journal of Medicine and Life Science
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• 제18권2호
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• pp.31-34
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• 2021

The pharmacokinetic properties of transdermal nicotine patches (TNPs) are different from those of other routes of nicotine administration; further, acute nicotine poisoning by TNPs may present with different clinical features. In the present report, we describe the case of a 23-year-old woman who was admitted to emergency department (ED) at Jeju National University Hospital with loss of consciousness. Five hours before the ED visit, she used multiple TNPs to attempt suicide. Initially, nausea and vomiting occurred, and the symptoms worsened over time. We immediately removed the TNPs, and the application sites were gently washed with sterile water. The patient's level of consciousness gradually improved, and she fully recovered an altered mental status 5 hours later. Her initial urinary cotinine level was 324 ng/mL. Physicians should be aware that acute nicotine poisoning by TNPs can cause various toxic symptoms.

• Biomolecules & Therapeutics
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• 제17권3호
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• pp.305-310
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• 2009

The aim of this study was to determine if a meloxicam hydrogel could be administered in vivo via phonophoretic transdermal delivery using pulsed ultrasound by examining its anti-hyperalgesic effects in a rat carrageenan inflammation model. Carrageenan (1%) was injected into the plantar surface of the right hindpaw, and meloxicam hydrogel was administered via phonophoretic transdermal delivery. Changes in the mechanical and thermal hyperalgesia, as well as swelling, showed that phonophoretic delivery of meloxicam exhibited significantly better anti-hyperalgesic and anti-inflammatory effects than pulsed ultrasound. Topical and systemic application of meloxicam hydrogel using phonophoresis showed similar anti-hyperalgesic effects. These findings suggest that the transdermal administration of a meloxicam hydrogel using phonophoresis by pulsed ultrasound might be useful for treating acute inflammation.

• Journal of Pharmaceutical Investigation
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• 제24권1호
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• pp.11-16
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• 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.