• The Journal of Korean Physical Therapy
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• v.13 no.3
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• pp.719-726
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• 2001

Transdermal drug delivery offers various advantages over conventional drug delivery systems, such as avoidance gastrointestinal degradation and hepatic first-pass effect. encourages patient compliance. and possible sustained release of drugs. However, transdermal transport of drugs is low permeability of the stratum corneum, the superficial layer of the skin. Many physicochemical and biological factors influencing transdermal transport is described together with the corresponding experimental and clinical results. Phonophoresis is medical treatment with drugs introduced into the skin by ultrasound energy. Enhanced drug penetration is through to result from the biophysical alterations of skin structure by ultrasound waves. The frequency used for phonophoresis is usually from 20 kHz to 15MHz. Phonophoresis can be categorized in to three ranges: low-frequency range(below 1 MHz). therapeutic frequency range(1 to 3MHz), and high-frequency range(above 3 MHz). The depth of penetration of ultrasound into skin is inversely proportional to the frequency. Cavitation may cause mechanical stress. temperature elevation, or enhanced chemical reactivity causing drug transport. One theory is that ultrasound affects the permeation of the stratum corneum lipid structure as the limiting step in permeating through the skin. The range of indications for phonophoresis is wide. Aspecific classification of the range of indications is obtained by classification of pathological conditions. The continuous research is needed for many interesting issucs of phonophoretic transdermal delivory in new future.

• Journal of the Korean Society of Physical Medicine
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• v.9 no.2
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• pp.133-140
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• 2014

PURPOSE: The purpose of this study was to compare the effect of current density on penetration depth, tissue concentration and transdermal transport of methylene blue(MB) by iontophoretic transdermal delivery. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into 1 mA($0.11mA/cm^2$), 2 mA($0.22mA/cm^2$), 4 mA($0.44mA/cm^2$), and 8 mA($0.89mA/cm^2$) groups. These rats were exposed to anodic iontophoresis of 1% MB using a direct current for 15 minutes. The penetration depth were measured using light microscopy from cryosections of skin tissue. The tissue concentration and transdermal transport were measured using biochemical analysis from target skin tissues. The data were analyzed with one-way analysis of variance. RESULTS: The significant differences in the penetration depth, tissue concentration and transdermal transport were detected among the groups(p<.001). Post hoc comparisons of the penetration depth, tissue concentration and transdermal transport of he 2 mA, 4 mA, and 8 mA iontophoresis groups were greater than in the 1 mA iontophoresis group(p<.05). There was no significant difference, however, among 2 mA, 4 mA, and 8 mA iontophoresis group. CONCLUSION: There was no difference in the efficiency of iontophoresis from 2 mA($0.22mA/cm^2$) to 8 mA($0.89mA/cm^2$). Higher current density can cause skin injury and discomfort sensation. In general, $0.5mA/cm^2$ is proposed to be the maximum iontophoretic current which should be used on human. The appropriate current amplitude should be selected by considering the safety current density and the depth of the target tissue.

• Journal of Pharmaceutical Investigation
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• v.40 no.1
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• pp.23-31
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• 2010

In our previous work on levodopa delivery at pH 2.5 using iontophoresis, we found that cathodal delivery showed higher permeation than anodal delivery and electroosmosis plays more dominant role than electrorepulsion. In this work, we studied the transdermal transport of levodopa at very low pH (pH=1.0) where all levodopa molecules are cations, and evaluated some factors which affect the transdermal transport. The transport study at pH 2.5 was also conducted for comparison. The contribution of electrorepulsion and electroosmosis on flux was also evaluated. Using stable aqueous solution, the effect of electrode polarity, current density, current type and drug concentration on transport through skin were studied and the results were compared. We also investigated the iontophoretic flux from hydroxypropyl cellulose (HPC) hydrogel containing levodopa. In vitro flux study was performed at $33^{\circ}C$, using side-by-side diffusion cell. Full thickness hairless mouse skin were used. Current densities applied were 0.2, 0.4 or $0.6\;mA/cm^2$. Contrary to the pH 2.5 result, anodal delivery showed higher flux, indicating that electrorepulsion is the dominant force for the transport, overcoming the electroosmotic flow which is acting against the direction of electrorepulsion. Cumulative amount of levodopa transported was increased as the current density or drug concentration was increased. When amount of current dose was constant, continuous current was more beneficial than pulsed current in promoting levodopa permeation. Similar transport results were obtained when hydrogel was used as the donor phase. These results indicate that iontophoretic delivery of zwitterion such as levodopa is much complicated than that can be expected from small ionic molecules. The results also indicate that, only at very low pH like pH 1.0, electrorepulsion can be the dominant force over the electroosmosis in the levodopa transport.

• Journal of Pharmaceutical Investigation
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• v.41 no.1
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• pp.9-17
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• 2011

The objective of this work is to study transdermal delivery of calcitonin using iontophoresis and to evaluate various factors which affect the transdermal transport. We have studied the effect of polarity, current density, drug concentration, penetration enhancers (isopropyl myristate [IPM] and ethanol) and laser treatment on transdermal flux and the results were compared. We also investigated the iontophoretic flux from microemulsions containing calcitonin together with oleic acid (OA) or IPM. In vitro flux study was performed at $33^{\circ}C$, using side-by-side diffusion cell and full thickness hairless mouse skin. Anodal delivery at pH 3.0 was much larger than cathodal and passive delivery, due to the positive charge of calcitonin. Cumulative amount delivered (CUM) by cathodal or passive delivery was close to zero for 10 hours. The pretreatment of skin by neat IPM markedly increased the CUM anodically. CUM increased as the current density, drug concentration or the duration of IPM treatment increased. Microemulsion containing IPM or oleic acid was prepared and the phase diagram was constructed. CUM also increased when IPM was incorporated into a microemulsion. OA microemulsion showed similar enhancing effect to IPM microemulsion. The delivery of calcitonin from 70% (v/v) ethanol aqueous solution showed a large increase in flux. Laser treatment of skin before flux experiment exhibited about 2 fold increase in total calcitonin amount transported for 12 hours, when compared to that delivered by IPM microemulsion. Based on these results, we have evaluated the possibility of delivering enough amount of calcitonin to reach the therapeutic level. The data suggest that it is highly possible to deliver clinically effective amount of calcitonin using iontophoresis patch with small area (<10 $cm^2$).

• Journal of Pharmaceutical Investigation
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• v.40 no.2
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• pp.91-100
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• 2010

The objective of this work is to study transdermal delivery of donepezil hydrochloride (DH) using iontophoresis and to evaluate various factors which affect the transdermal transport. After the flux study using 4 kinds of hydrogel, hydrogel containing 8% poly(ethylene oxide) (PEO) was chosen as the hydrogel for further studies. Under experimental condition, DH was stable. We have studied the effect of polarity, current density, drug concentration and current profile on transdermal flux and compared the results. In vitro flux study was performed at $33^{\circ}C$, using side-by-side diffusion cell and full thickness hairless mouse skin. DH is positively charged at pH 7.4, and anodal delivery was much larger than cathodal and passive delivery at all current densities studied (0.2, 0.4 and 0.6 mA/$cm^2$). Cathodal delivery showed higher flux than passive flux. Flux increased as the concentration of DH in hydrogel increased. Pulsatile application of current showed smaller flux value than the application of continuous current. Based on these results, we have evaluated the possibility of delivering enough amount of DH to reach the therapeutic level. The maximum cumulative amount of DH transported for 12 hours was 455 ${\mu}g/cm^2{\cdot}hr$ when the amount of DH in the hydrogel was 3 mg/mL and the current density was 0.4 mA/$cm^2$. If the patch size is 10 $cm^2$, then we can deliver 4.6 mg for 12 hours. Because the daily dosage of DH is 5 mg, it seems possible to deliver clinically effective amount of DH using iontophoresis. This study also provides some information about the role of electrorepulsion and electroosmosis during the transport through skin.

• Journal of Pharmaceutical Investigation
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• v.29 no.4
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• pp.337-341
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• 1999

We have studied the stability and transdennal flux of prostaglandin $E_1\;(PGE_1)$ from various donor solutions through hairless mouse skin. Stability in HEPES buffer or in propylene glycol (PG) solution where enhancer (oleic acid (OA), propylene glycol monolaurate (PGML), transcutol (TC), ethanol (EtOH))s dissolved was investigated. $$PGE_1 was not stable in HEPES buffer. The concentration of $$PGE_1 decreased continuously for 7 days, and the degradation rate constant was $0.0028\;h^{-1}$, assuming first order reaction. The effect of current or penetration enhancer on the degradation was minimal. Percutaneous transport from HEPES buffer by passive or iontophoretic delivery without enhancer was close to nil. When OA or PGML was used together with PG, both passive and iontophoretic flux increased. PGML showed better enhancing effect than OA. Flux by cathodal delivery was about 2 times larger than that by passive delivery. Flux by anodal delivery was lower than that by passive delivery. TC and EtOH also increased the transdermal flux, but the effect was not as good as that observed when OA or PGML was used. These stability and flux data provide important information on how to formulate the patch, which will be the next step of this work, and on the polarity of current to use during iontophoresis.

• The Journal of Korean Physical Therapy
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• v.23 no.6
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• pp.77-84
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• 2011

Purpose: The objectives of this study were to determine the enhancing effect of iontophoresis method as it transdermally deliver methylene blue (MB) using visual examination, in terms of penetration depth and tissue distribution in the skin, and to determine the effect of application duration on the efficacy of iontophoresis. Methods: Twenty-four male Sprague-Dawley rats were randomly divided into 5-, 10-, 20-, and 40-minute groups. These rats were exposed to either topical or anodic iontophoresis of 1% MB using a direct current of $0.5mA/cm^2$ for 5, 10, 20, and 40 minutes. Using cryosections of rat tissues, the penetration depth of MB was measured using light microscopy. Results: Significant differences in the penetration depth (F=54.20, p<0.001) were detected among the four groups. Post hoc comparisons of the penetration depth of MB data pooled across groups showed no significant difference between all topical application groups and 5-minute iontophoresis group, but did reveal a significant difference in the penetration depth between all topical application groups and 5-minute iontophoresis group versus 10-minute group, between the 10-minute and 20-minute group, and between the 20-minute and 40-minute iontophoresis group (p<0.05). Conclusion: The results demonstrate that iontophoresis enhances transdermal delivery of MB across stratum corneum of skin barrier by visual examination. Furthermore, the penetration depth of iontophoretic transdermal delivery of MB was dependent on the application duration. The duration of iontophoresis is one of the important factor in the efficacy of iontophoresis application.

• Journal of Pharmaceutical Investigation
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• v.38 no.1
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• pp.31-38
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• 2008

The objective of this work is to study transdermal delivery of levodopa using iontophoresis and evaluate various factors which affect the transdermal transport. Levodopa is unstable in aqueous solution, and, in order to establish a stable condition for levodopa for the duration of experiment, we investigated the stability of levodopa in aqueous solutions of different pHs with/without the addition of dextrose or the application of current. Using stable aqueous solution, we have studied the effect of pH, polarity and penetration enhancer (ethanol) on transdermal flux and compared the results. We also investigated the iontophoretic flux from hydroxypropyl cellulose (HPC) hydrogel. In vitro flux study was performed at $33^{\circ}C$, using side-by-side diffusion cell. Full thickness hairless mouse skin and rat skin were used for this work. Current densities applied were 0.4 or $0.6mA/cm^2$ and current was off after 6 hour application. Stability study showed that levodopa solution with a pH 2.5 or 4.5 maintained the initial concentration of levodopa for 24 hours with the addition of 5% dextrose. However, at pH 9.5, levodopa was unstable and 30 to 40% of levodopa degraded within 24 hours, even with the addition of 5% dextrose. Hydrogel swollen with dextrose added levodopa solution maintained about 97% of the initial concentration of levodopa for 13 days, when stored in $4^{\circ}C$. The application of current did not affect the stability of levodopa in hydrogel. Flux study from levodopa solution with pH 2.5 showed that cathodal delivery of levodopa was higher than passive or anodal delivery. When the pH of the donor solution was 4.5, anodal delivery of levodopa was higher than passive or cathodal delivery. These results seem to indicate that electroosmosis plays more dominant role than electrorepulsion in the flux of levodopa at pH 2.5, and the reverse situation applies for pH 4.5. The passive flux was unexpectedly high for the ionized levodopa. Similar to the results from aqueous solution, cumulative amount of levodopa transported trom HPC hydrogel by cathodal delivery was significantly higher than passive or anodal delivery. The treatment of 70% ethanol cotton ball by scrubbing increased passive, anodal and cathodal flux, with the largest increase for anodal flux. These results indicate that iontophoretic delivery of zwitterion such as levodopa is much complicated than that can be expected from small ionic molecules with single charge. The results also indicate that the balance between electroosmosis and electrorepulsion plays a very important role in the transport through skin.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.232.2-232.2
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• 2003

Transdermal iontophoresis is a physical enhancement technique to facilitate the delivery of primarily charged molecules across the skin. Principal mechanism of iontophoresis is electrorepulsion experienced by the charged solutes under the application of a potential gradient. In this work, we have investigated several factors (concentration of NADPH, current density) that can affect the iontophoretic flux. We also studied the stability of NADPH in aqueous solution with/without various antioxidants such as butylated hydroxy toluene (BHT). (omitted)

• Bulletin of the Korean Chemical Society
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• v.28 no.9
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• pp.1535-1538
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• 2007

The work presented in this paper represents a study of the rate and extent of transdermal penetration of three synthetic hexapeptides consisting only of glycine (Gly) and phenylalanine (Phe) as the constituent amino acids and they include Phe-Gly-Gly-Gly-Gly-Gly (Pep-1), Phe-Phe-Gly-Gly-Gly-Gly (Pep-2), and Phe-Phe-Phe- Gly-Gly-Gly (Pep-3). The present study demonstrated the extent to which the peptides having a high metabolic stability were transdermally transported from the various vehicles. The results of this study appear to indicate that minor differences in the lipophilicity of the synthetic hexapeptides have a slight influence on the rate and extent of transport. In the presence of terpene permeation enhancers, together with ethanol (i.e., menthone/ EtOH, carveol/EtOH or cineole/EtOH), the peptides were more rapidly penetrated through the skin and among the terpenes tested, cineole was the most effective for all three peptides. The maximum enhancement ratio of approximately 2 was achieved by cineole in 50% ethanol solution.