A Review of Selected Investigational Nonsteroidal Antiinflammatory Drugs of the 1980s

Marsh, Charles C.; Schuna, Arthur A.; Sundstrom, Walter R.

doi:10.1002/j.1875-9114.1986.tb03445.x

Cited by 38 publications

(18 citation statements)

References 98 publications

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“…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.…”

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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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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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“…DFS has 60% oral bioavailability and an excretion half-life of 1.1-1.8 h with high protein binding [Marsh et al, 1986;Todd and Sorkin, 1988]. With it's short plasma half-life and multiple dosing regimen, it has the propensity of systemic accumulation leading to side effects or at times severe systemic toxicity in the central nervous system, gastrointestinal system, and cardiovascular system when used in the long-term treatment of various arthritic conditions [Wilkens, 1985;Marsh et al, 1986]. About 2% of patients discontinue therapy because of adverse effects [Small, 1989].…”

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confidence: 99%

Formulation and comparative evaluation of controlled release diclofenac tablets prepared by matrix‐embedding technique, membrane barrier technique, and combination of the two

Sajeev

Saha

2001

Drug Development Research

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The need for controlled release formulations of diclofenac sodium (DFS) tablets is well recognized. In this study, controlled release tablets of DFS were formulated using ethyl cellulose as retardant by matrix-embedding technique, the membrane barrier technique, and a combination of the two. Tablets of all the formulations were found to be of good physical quality with respect to appearance, drug content uniformity, hardness, weight variation, friability, and coat thickness uniformity. In vitro release rate studies showed that increasing the proportion of ethyl cellulose extended the release of DFS. In the case of polymer-coated tablets, an increase in the thickness of the coat (by increasing the concentration of the coating solution or by increasing the number of coats applied) controlled and extended the release. The release pattern was found to follow Higuchi's square root kinetics in matrix-embedded tablets and zeroorder kinetics in polymer-coated tablets. However, for an ideal controlled release formulation of watersoluble drugs like DFS, a combination of both matrix-embedding and the membrane barrier technique was found to be a better proposition for extended release beyond 12 h. Such formulations exhibited dual control: matrix-embedding controlled the release rate in the initial 3-4 h of release and membrane coat-controlled the release profile after that. At pH 6.8, the release rate was higher, probably due to increased solubility of DFS and/or increased swelling of ethyl cellulose at higher pH. However, reduction in the granule size in matrix-embedded tablets provided a more controlled and extended release due to more tortuosity and compaction. All the formulations were found to be highly stable and possessed reproducible release kinetics across the batches. Drug Dev. Res. 53:1-8, 2001.

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“…Indomethacin is also reported to decrease EP2 prostanoid receptor expression in colon cancer cells (7). When administered orally as an immediate release formulation, it results in side effects and toxicities due to systemic accumulation of the drug (8). Therefore, a colon-specific formulation of indomethacin would achieve high local concentrations of drug in the colon with reduced systemic absorption, and thereby maximize therapeutic efficacy of the drug in the treatment of this disease.…”

Section: Introductionmentioning

confidence: 99%

Design and in vitro evaluation of formulations with pH and transit time controlled sigmoidal release profile for colon-specific delivery

et al. 2009

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A Review of Selected Investigational Nonsteroidal Antiinflammatory Drugs of the 1980s

Cited by 38 publications

References 98 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

Formulation and comparative evaluation of controlled release diclofenac tablets prepared by matrix‐embedding technique, membrane barrier technique, and combination of the two

Design and in vitro evaluation of formulations with pH and transit time controlled sigmoidal release profile for colon-specific delivery

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