The effect of iontophoresis and vehicle pH on the in-vitro permeation of lignocaine through human stratum corneum

Siddiqui, Ovais; Roberts, Michael S.; Polack, Alan E.

doi:10.1111/j.2042-7158.1985.tb04954.x

Cited by 84 publications

(31 citation statements)

References 5 publications

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“…We employed lidocaine (LC, pK a ϭ7.9) 15) and ketoprofen (KP, pK a ϭ4.0) 16) as model basic and acidic drugs, respectively. The drugs were dissolved in buffer solutions with several pHs so that we could evaluate the effect of the sugar esters on the percutaneous permeation of ionized and unionized drug species.…”

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confidence: 99%

Effect of Sucrose Fatty Acid Esters on Transdermal Permeation of Lidocaine and Ketoprofen

Okamoto

Sakai

Danjo

2005

Biological & Pharmaceutical Bulletin

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Skin has many advantages as a site for local and systemic drug administration. However, the barrier properties of the outermost layer, the stratum corneum, have limited the number of successful transdermal dosage forms developed thus far. One of the strategies for overcoming this problem is temporary local reduction of the barrier function of the stratum corneum with the aid of a percutaneous absorption enhancer.Sucrose fatty acid esters (sugar esters) are nonionic surfactants with sucrose as the polar head group and one or several fatty acid chains as the lipophilic moiety. Some of them are legally approved as food additives due to their high safety 1) and are registered as pharmaceutical excipients in Japan, USA, Canada, Australia, and New Zeeland.2) Sugar esters have low irritancy to the skin and eyes. 1) There have been several reports or patents about utilizing sugar esters as additives for drug formulations. Some sugar esters enhance gastrointestinal absorption of elastase 3) and blactam antibiotics.4) The nasal mucosal absorption of peptides such as calcitonin, 5) interferon, 6) and a-human atrial natriuretic polypeptide 7) are increased by sucrose laurate or sucrose stearate. Sucrose palmitate enhances the absorption of calcitonin from the oral mucosa 8) and gingiva 9) in rats. Ganem-Quintanar et al. examined the effect of sucrose stearate, oleate, palmitate, and laurate on the permeation of lidocaine hydrochloride through excised pig palate and cheek and reported that only sucrose laurate acted as an absorption enhancer.10) Some sugar esters act as percutaneous absorption enhancers. It has been reported that sucrose stearate and sucrose laurate increase percutaneous absorption of bromhexine in rats 11) and oestradiol in rabbits, 12) respectively. The percutaneous absorption of diltiazem and hydromorphone are also aided by some sugar esters. 13,14) Nakada et al. examined the effect of more than 10 sugar esters with HLB ranging 2 to 16 on the absorption of calcitonin from oral mucosa in rats.8) An enhancing effect was found for sugar esters with HLB values ranging from 11 to 16. However, the effect of the length of the fatty acid chain and HLB of sugar esters on their activity as percutaneous absorption enhancers has not been reported.In the present study, we selected six sugar esters with HLB 5-16 and evaluated their effect on percutaneous drug permeation in in vitro experiments using excised hairless mouse skin. We employed lidocaine (LC, pK a ϭ7.9) 15) and ketoprofen (KP, pK a ϭ4.0) 16) as model basic and acidic drugs, respectively. The drugs were dissolved in buffer solutions with several pHs so that we could evaluate the effect of the sugar esters on the percutaneous permeation of ionized and unionized drug species.It has been reported that sugar esters form micelles in water and in an organic solvent.17) The micelles would affect the thermodynamic properties of a penetrant in a vehicle. To examine the effect of sugar esters on skin permeability and to minimize the effect on vehicle or interaction wi...

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confidence: 99%

Effect of Sucrose Fatty Acid Esters on Transdermal Permeation of Lidocaine and Ketoprofen

Okamoto

Sakai

Danjo

2005

Biological & Pharmaceutical Bulletin

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“…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.…”

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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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“…Studies have shown that the iontophoretic delivery of local anesthetics is dependent upon the pKa and pH of the solution. 37,38 In addition, studies have demonstrated that the iontophoretic delivery of local anesthetics does not depend upon the concentration of the solution. 36 From our study, it appears that this phenomenon also holds true for EP.…”

Section: Discussionmentioning

confidence: 99%

Topical delivery of lidocaine in healthy volunteers by electroporation, electroincorporation, or iontophoresis: An evaluation of skin anesthesia

Wallace

2001

Regional Anesthesia and Pain Medicine

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The effect of iontophoresis and vehicle pH on the in-vitro permeation of lignocaine through human stratum corneum

Cited by 84 publications

References 5 publications

Effect of Sucrose Fatty Acid Esters on Transdermal Permeation of Lidocaine and Ketoprofen

Effect of Sucrose Fatty Acid Esters on Transdermal Permeation of Lidocaine and Ketoprofen

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

Topical delivery of lidocaine in healthy volunteers by electroporation, electroincorporation, or iontophoresis: An evaluation of skin anesthesia

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