• Journal of Pharmaceutical Investigation
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• v.40 no.3
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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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• v.36 no.3
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• pp.185-192
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• 2006

The purpose of this study was to determine the effects of iontophoresis on transdermal delivery of procaine hydrochloride in healthy volunteers, as well as to the synergic effect of high voltage current or ultrasound on the efficacy of transdermal delivery of iontophoresis. Forty healthy volunteers were randomly assigned to four groups topical application group (TA), iontophoresis group (IT), pre-treatment of high voltage current stimulation with iontophoresis (HVS + IT), and pre-treatment of ultrasound application with iontophoresis (US + IT). All subjects received procaine iontophoresis on the forearm using direct current with 4 mA f3r 15 minutes. All subject was measured the duration of local anesthesia, pressure pain threshold, pain perception threshold using rectangular wave at 0.2 ms, 1 ms, 50 ms of rectangular current stimulation after procaine iontophoresis. For comparisons of the sensory characteristics and efficacy of iontophoresis between the groups, an one-way ANOVA and Kruskal-Wallis were used. The significant difference the duration of local anesthesia were found between the groups (p<0.001). The local anesthetic duration of IT, HVS+IT were significantly longer than TA. Meanwhile, the local anesthetic duration of US+IT was significantly longer than HVS+IT, IT and TA group (p<0.05). Also, the pressure pain threshold, pain perception threshold at 0.2 ms, 1 ms, 50 ms were significant difference between the groups (p<0.001). All sensory characteristics including pressure pain threshold, pain perception threshold of IT, HVS+IT was significantly increased than TA, whereas, US+1T was significantly increased HVS+1T, IT and TA (p<0.05). This study showed that the procaine iontophoresis have increase the duration of local anesthesia concomitantly pressure pain threshold and pain perception threshold of sensory nerve fibers such as $A-{\beta}$, $A-{\delta}$ and C fiber. This findings suggest that the iontophoresis enhanced the transdermal delivery of drug ions in vivo. The combination of ultrasound application and iontophoresis synergized the transdermal delivery of drug ions. It is suggests that an electric field, mechanical and heating property of ultrasound may contribute to synergic effect due to temporary changes of structure in the stratum corneum.

• Polymer(Korea)
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• v.33 no.3
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• pp.237-242
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• 2009

This study examined the transdermal delivery of alendronate across hairless mouse skin. The effects of iontophoresis, perforation with a microneedle, and a combination of a microneedle pretreatment and iontophoresis were evaluated in vitro test. Hydrogel patches were polymerized by UN polymerization to supply a hydrogel patch to the iontophoretic transdermal drug delivery system. The alendronate content in the iontophoretic delivery patch was $5.0\;mg/cm^3$. The amounts of alendronate that permeated across the hairless mouse skin when current densities of 0.25 and $0.50\;mA/cm^2$ were supplied to the iontophoretic alendronate patch were $0.80{\pm}0.03$ and $2.00{\pm}0.02{\mu}g$, respectively. After pretreatment with a microneedle, the amounts of alendronate that permeated across the hairless mouse skin increased to $70.65{\pm}0.37$ and $162.23{\pm}0.40{\mu}g$, respectively. The biocompatibility of the iontophoretic alendronate patch was examined according to the international standardization organization 10993.

• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.106-110
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• 2010

The pharmacokinetics and bioavailability of ambroxol, an expectoration improver and mucolytic agent, were studied to determine the feasibility of enhanced transdermal delivery of ambroxol from the ethylene-vinyl acetate (EVA) matrix system containing polyoxyethylene-2-oleyl ether as an enhancer in rats. The ambroxol-010 matrix system (15 mg/kg) was applied to abdominal skin of rats. Blood samples were collected via the femoral artery for 28 hrs and the plasma concentrations of ambroxol were determined by HPLC. Pharmacokinetic parameters were calculated using Lagran method computer program. The area under the curve (AUC) was significantly higher in the enhancer group ($1,678{\pm}1,413.3\;ng/ml{\cdot}hr$) than that in the control group $1,112{\pm}279\;ng/ml{\cdot}hr$), that is treated transdermally without enhancer, showing about 151% increased bioavailability (p<0.05). The average $C_{max}$ was increased in the enhancer group ($86.0{\pm}21.5\;ng$/ml) compared with the control group ($59.0{\pm}14.8\;ng$/ml). The absolute bioavailability was 13.9% in the transdermal control group, 21.1% in the transdermal enhancer group and 18.1% in the oral administration group compared with the IV group. The $T_{max}$, $K_a$, MRT and $t_{1/2}$ of ambroxol in transdermal enhancer group were increased significantly (p<0.01) compared to those of oral administration. As the ambroxol-EVA matrix containing polyoxyethylene-2-oleyl ether and tributyl citrate was administered to rats via the transdermal routes, the relative bioavailability increased about 1.51-fold compared to the control group, showing a relatively constant, sustained blood concentration. The results of this study show that ambroxol-EVA matrix could be developed as a transdermal delivery system providing sustained plasma concentration.

• Archives of Pharmacal Research
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• v.18 no.4
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• pp.224-230
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• 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
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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 Adhesion and Interface
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• v.4 no.1
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• pp.43-50
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• 2003

점착제는 경피흡수제제(transdermal drug delivery system, TDDS)의 중요한 구성요소 중의 하나이다. TDDS용 점착제는 일반적인 점착제의 역할 외에도 부착되는 피부에 적합해야 하고, 이것에 포함되는 약물 및 첨가제들과 양립하면서 약물의 전달을 효과적으로 지속해야한다. 본 총설에서는 흔히 사용되는 TDDS용 점착제인 polyisobutylenes, polyacrylates, silicones와 최근에 개발된 제품들을 소개한다.

• The Journal of Korean Physical Therapy
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• v.15 no.2
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• pp.182-195
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• 2003

This study investigated the effects of triamcinolone acetonide by iontophoretic transdermal drug delivery on anti-inflammatory action into the rats and which had carrageenan-induced hyperalgesia and edema in the feet, trauma-induced tissue damage in the thigh. Each group was treated under the fellowing conditions. 1. Group I : Control group 2. Group II : Application of direct current 3. Group III : Application of 0.1$\%$ triamcinolone acetonide solution 4. Group IV : Iontophoresis of 0.1$\%$ triamcinolone acetonide solution The degree of anti-inflammation was evaluated by the paw withdrawal latency, the change in volume of foot the change of paw edema, histological change in rats. 1. In paw withdrawal latency, group IV showed the most significant therapeutic effect than the other groups at 0, 3, 6 and 9 hours(p < 0.001). 2. In paw edema experiment in the foot, group IV showed the most significant effect than group I at 0, 3, 6 and 9 hours. It meant that there was effective anti-inflammatory reaction in group I (p < 0.001). 3. In the light microscopic observation, group IV showed the most significant reduction of haemorrhage, hyperemia and infiltrative inflammation. From the results, the iontophoresis with triamcinolone acetonide is more effective than using each groups. It is one of the effective physical agent which delivered large molecular weight drug into the body. The continuous study is needed for many interesting issues of iontophoretic transdermal drug delivery in new future.

• The Journal of Korean Physical Therapy
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• v.18 no.4
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• pp.41-50
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• 2006

Purpose: The purpose of this study was to determined that the efficacy and comfort of iontophoretic transdermal delivery of lidocaine by comparison of local anesthetic duration, sensory threshold, pain threshold and pain tolerance levels according to four different cleansing regimes. Methods: Forty healthy volunteers were randomly assigned to four groups; oil cleansing group, lotion cleansing group, solution cleansing group and alcohol cleansing group. All subjects were received lidocaine iontophoresis on the forearm using direct current with 4 mA for 10 minutes. All subjects were measured the duration of local anesthesia after lidocaine iontophoresis, also evaluated the sensory threshold, pain threshold and pain tolerance level during iontophoresis. For comparisons of the efficacy and the sensory characteristics of iontophoresis within the groups, an one-way ANOVA was used. Results: The duration of local anesthesia were found significant difference between groups (p<0.001). The anesthetic duration in solution and alcohol cleansing groups were significantly longer than oil and lotion cleansing group by post hoc (p<0.05). Statistically significant difference were noted in respect to all sensory characteristics such as sensory threshold, pain threshold and pain tolerance between groups (p<0.001). The sensory threshold in solution and alcohol cleansing group were significantly lower than oil and lotion cleansing group by post hoc using Duncan multiple range test (p<0.05). The pain threshold and pain tolerance in solution and alcohol cleansing group were significantly higher than oil and lotion cleansing group by post hoc (p<0.05). Conclusion: These results demonstrated that cleansing regimes have affected the efficacy and discomfort of iontophoretic transdermal delivery of lidocaine. These findings indicate that cleansing agents without oil ingredient contributed to more comfort, and more successful achievement of the iontophoretic transdermal delivery.

• Journal of Pharmaceutical Investigation
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• v.35 no.5
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• pp.329-332
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• 2005

HPMC-based novel gel formulations for the transdermal delivery of testosterone (TS) were developed, and the effect of various skin permeation enhancers was studied in vitro and in vivo. In vitro hairless mouse skin permeation of TS from the gel was investigated using Keshary-Chien diffusion cells for 8 hours at $37^{\circ}C$. In vivo plasma concentration profiles of TS after applying the gel on the abdominal skin of rat were determined using a commercial radioimmunoassay kit. Hairless mouse skin permeation of TS increased with the addition of permeation enhancers both in vitro and in vivo. Combination of diethanolamine (2%) and N-methylpyrrolidone (NMP, 6%) was the most effective among tested. Plasma concentration of TS significantly increased for at least 24 hours with the addition of diethanolamine and NMP. These results suggest the feasibility of the development of a HPMC-based gel formulation for the transdermal delivery of TS.