Comparison of Depolarizing and Direct Current Systems on Iontophoretic Enhancement of Transport of Sodium Benzoate Through Human and Hairless Rat Skin

Numajiri, Sachihiko; Sakuraï, H.; Sugibayashi, Kenji; Morimoto, Yasunori; Omiya, Harumi; Takenaka, Haruyuki; Akiyama, Noriyoshi

doi:10.1111/j.2042-7158.1993.tb05662.x

Cited by 14 publications

(5 citation statements)

References 12 publications

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“…5) Since an optimal iontophoretic effect requires maximal ionization, 6,7) effective drug transport must minimize pH changes in the drug-containing solution. In order to overcome these disadvantages, systems using a silver or silver-silver chloride electrode 8,9) or pulsed direct current 10) have been investigated. However, there have been few reports demonstrating both safety and drug availability when iontophoretic systems were used in vivo.…”

mentioning

confidence: 99%

In Vivo Transdermal Delivery of Diclofenac by Ion-Exchange Iontophoresis with Geraniol

Kigasawa

Kajimoto

Watanabe

et al. 2009

Biological & Pharmaceutical Bulletin

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Iontophoresis is a promising method which utilizes an electric field to enhance the delivery of charged compounds across skin.1,2) Since drug administration is readily controlled by adjustment of the applied voltage or current, iontophoresis may become a useful technique for drug therapy at home. Conventional iontophoretic systems use direct current which frequently causes skin irritation due to change in pH 3) or continuous electrical polarization of the skin.4) Moreover, changes in pH alter the ionization of organic compounds which exist in a pH-dependent equilibrium between their ionized and nonionized states. 5) Since an optimal iontophoretic effect requires maximal ionization, 6,7) effective drug transport must minimize pH changes in the drug-containing solution. In order to overcome these disadvantages, systems using a silver or silver-silver chloride electrode 8,9) or pulsed direct current 10) have been investigated. However, there have been few reports demonstrating both safety and drug availability when iontophoretic systems were used in vivo.Recently, a novel iontophoretic device was developed by TTI ellebeau Inc. to improve the capabilities of current systems (Fig. 1). This novel system transfers an ionic drug from the drug solution into the skin through an ion-exchange membrane. The counter ions are transported from the drug solution to an electrode buffer compartment, and do not pass from the skin into the drug solution due to the presence of the ion-exchange membrane. In this way, the balance between cations and anions in the drug solution can be kept constant. It is assumed that changes in pH due to oxidation and reduction reactions at the anode and cathode do not affect the conditions of the drug-containing solution, because the drug solution chamber and the electrode chamber are separated by ion-exchange membrane. It is also assumed that insults to the skin are relatively minor compared with conventional devices since the influx of endogenous ions from the skin into the drug solution is prevented by the presence of the ion-exchange membranes.Transdermal delivery of non-steroidal anti-inflammatory drugs (NSAIDs) by iontophoresis would be advantageous since it would avoid hepatic first-pass metabolism and considerable gastrointestinal disturbances.11,12) However, as presently configured, iontophoretic delivery of anionic compounds, such as NSAIDs, is relatively inefficient because the negative charge on the surface of the skin electrostatically repels anionic drugs.13) Therefore, further improvements in iontophoresis systems are required for efficient transdermal delivery of anionic drugs. The purpose of this study was to examine transdermal delivery of the anionic pharmacologic agent diclofenac sodium, a widely used NSAID, by a novel iontophoretic system. Previously, in vitro iontophoresis of insulin was enhanced by pretreatment of skin with a chemical A novel iontophoretic system utilizing ion-exchange membranes is effective for selective transdermal delivery of ionized drugs. In the present stu...

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confidence: 99%

In Vivo Transdermal Delivery of Diclofenac by Ion-Exchange Iontophoresis with Geraniol

Kigasawa

Kajimoto

Watanabe

et al. 2009

Biological & Pharmaceutical Bulletin

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“…Numajiri et al compared the percutaneous absorption of sodium benzoate between direct current (DC) (0.1 mA/cm 2 ) and PDC (3 mA/cm 2 , rectangular waveform, 40 kHz and 30% duty cycle). 5) They reported that the amount of drug absorbed was almost equal and PDC was more suitable in terms of skin irritation. Zakzewski et al 6) and Bagniefski et al 7) also showed an equivalent absorption between DC and PDC.…”

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Evaluation of Skin Barrier Function Using Direct Current II: Effects of Duty Cycle, Waveform, Frequency and Mode.

Kanebako¹,

Inagi²,

Takayama

2002

Biological & Pharmaceutical Bulletin

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The aim of this study was to evaluate the reduction in skin barrier function caused by pulsed iontophoresis by measuring resistance in the short term. Experiments under direct current (DC) and pulsed direct current (PDC) conditions were carried out using rat abdominal skin in vivo. The resistance was measured every 62.5 m ms and analyzed using a two-compartment model consisting of surface and skin resistance. Moreover, the initial value and the rate constant of surface resistance were calculated with the non-linear approximation program. Using this method, effects of duty cycle, waveform, frequency and mode on the skin barrier function were examined. The barrier function decreased with increasing duty cycle. With regard to waveforms, the influence on the skin barrier function was greatest in the order of sine, rectangular, saw and triangular waveforms. A frequency of less than 100 Hz reduced the barrier function. Considering the reduction in barrier function and skin polarization, the PDC of a rectangular waveform (around 75% as duty cycle and less than 100 Hz as frequency) or sine waveform was most suitable. In addition, the difference in the amount of drug delivered by DC and by PDC was discussed.

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“…There are reports on the efficiency in the substances delivery through the skin by pulsed direct current (PDC), without causing burning and discomfort risk when compared to CDC. On the other hand, some authors have found greater, smaller or equal efficacy between CDC and PDC for substances delivery into the skin by iontophoresis [ 16 – 19 ].…”

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Pulsed direct and constant direct currents in the pilocarpine iontophoresis sweat chloride test

et al. 2014

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BackgroundThe classic sweat test (CST) is the golden standard for cystic fibrosis (CF) diagnosis. Then, our aim was compare the production and volume of sweat, and side effects caused by pulsed direct current (PDC) and constant direct current (CDC). To determine the optimal stimulation time (ST) for the sweat collection. To verify the PDC as CF diagnosis option.MethodsProspective study with cross-sectional experimental intervention. Experiment 1 (right arm): PDC and CDC. ST at 10 min and sweat collected at 30 min. Currents of 0.5; 0.75; 1.0 and 1.5 mA and frequencies of 0, 200, 1,000 and 5,000 Hz applied. Experiment 2 (left arm): current of 1.0 mA, ST at 5 and 10 min and sweat collected at 15 and 30 min with frequencies of 0; 200; 1,000 and 5,000 Hz applied Experiments 1 and 2 were performed with current density (CD) from 0.07 to 0.21 mA/cm2. Experiment 3: PDC was used in typical CF patients with two CFTR mutations screened and or with CF diagnosis by rectal biopsy and patients with atypical CF.Results48 subjects (79.16% female) with average of 29.54 ± 8.87 years old were enrolled. There was no statistical difference between the interaction of frequency and current in the sweat weight (p = 0.7488). Individually, positive association was achieved between weight sweat and stimulation frequency (p = 0.0088); and current (p = 0.0025). The sweat production was higher for 10 min of stimulation (p = 0.0023). The sweat collection was better for 30 min (p = 0.0019). The skin impedance was not influenced by ST and sweat collection (p > 0.05). The current frequency was inversely associated with the skin impedance (p < 0.0001). The skin temperature measured before stimulation was higher than after (p < 0.0001). In Experiment 3 (29 subjects) the PDC showed better kappa index compared to CDC (0.9218 versus 0.5205, respectively).ConclusionsThe performance of the CST with CDC and PDC with CD of 0.14 to 0.21 mA/cm2 showed efficacy in steps of stimulation and collection of sweat, without side effects. The optimal stimulation time and sweat collection were, respectively, 10 and 30 min.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2466-14-198) contains supplementary material, which is available to authorized users.

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Comparison of Depolarizing and Direct Current Systems on Iontophoretic Enhancement of Transport of Sodium Benzoate Through Human and Hairless Rat Skin

Cited by 14 publications

References 12 publications

In Vivo Transdermal Delivery of Diclofenac by Ion-Exchange Iontophoresis with Geraniol

In Vivo Transdermal Delivery of Diclofenac by Ion-Exchange Iontophoresis with Geraniol

Evaluation of Skin Barrier Function Using Direct Current II: Effects of Duty Cycle, Waveform, Frequency and Mode.

Pulsed direct and constant direct currents in the pilocarpine iontophoresis sweat chloride test

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