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      Journal of Pain Research (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on reporting of high-quality laboratory and clinical findings in all fields of pain research and the prevention and management of pain. Sign up for email alerts here.

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      Visualization of Epidermal Reservoir Formation from Topical Diclofenac Gels by Raman Spectroscopy

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          Abstract

          Purpose

          This work investigated whether topical pain relief diclofenac gels can form a diclofenac reservoir in the epidermal and dermal layers of human skin.

          Methods

          Excised human skin samples were treated with three topical diclofenac gels ex vivo and examined using Raman microscopy of transversally microtomed sections. The relative diclofenac concentration in the skin layers was calculated as the ratio of the integrated areas of bands characteristic of diclofenac (~445 cm −1) and skin (Amide I). A customized masking algorithm ensured that only diclofenac-specific signal was mapped in the resulting Raman images.

          Results

          A heterogenous spatial distribution of diclofenac was clearly visible in both the epidermis and the dermis in all samples, with a markedly higher diclofenac relative content and number of pixels above the detection limit in the epidermis compared to the dermis.

          Conclusion

          The Raman images evidenced that the studied topical gels deliver diclofenac through the stratum corneum skin barrier and form a drug depot localized in the epidermis. The data are in line with earlier clinical findings that this depot acts like a true reservoir and enables sustained drug release.

          Most cited references13

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          Modeling the human skin barrier--towards a better understanding of dermal absorption.

          Many drugs are presently delivered through the skin from products developed for topical and transdermal applications. Underpinning these technologies are the interactions between the drug, product and skin that define drug penetration, distribution, and elimination in and through the skin. Most work has been focused on modeling transport of drugs through the stratum corneum, the outermost skin layer widely recognized as presenting the rate-determining step for the penetration of most compounds. However, a growing body of literature is dedicated to considering the influence of the rest of the skin on drug penetration and distribution. In this article we review how our understanding of skin physiology and the experimentally observed mechanisms of transdermal drug transport inform the current models of drug penetration and distribution in the skin. Our focus is on models that have been developed to describe particular phenomena observed at particular sites of the skin, reflecting the most recent directions of investigation. Copyright © 2012 Elsevier B.V. All rights reserved.
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            Systemic bioavailability of topical diclofenac sodium gel 1% versus oral diclofenac sodium in healthy volunteers.

            Systemic bioavailability and pharmacodynamics of topical diclofenac sodium gel 1% were compared with those of oral diclofenac sodium 50-mg tablets. In a randomized, 3-way crossover study, healthy volunteers (n = 40) received three 7-day diclofenac regimens: (A) 16 g gel applied as 4 g to 1 knee 4 times daily (4 g on surface area 400 cm(2)), (B) 48 g gel applied as 4 g per knee 4 times daily to 2 knees plus 2 g gel per hand applied 4 times daily to 2 hands (12 g on 1200 cm(2)), and (C) 150 mg oral diclofenac applied as 50-mg tablets 3 times daily. Thirty-nine participants completed all 3 regimens. Systemic exposure was greater with oral diclofenac (AUC(0-24), 3890 +/- 1710 ng x h/mL) than with topical treatments A (AUC(0-24), 233 +/- 128 ng x h/mL) and B (AUC(0-24), 807 +/- 478 ng x h/mL). Oral diclofenac inhibited platelet aggregation, cyclooxygenase-1 (COX-1), and COX-2. Topical diclofenac did not inhibit platelet aggregation and inhibited COX-1 and COX-2 less than oral diclofenac. Treatment-related adverse events were mild and limited to application site reactions with diclofenac sodium gel 1% (n = 4) and gastrointestinal reactions with oral diclofenac (n = 3). Systemic exposure with diclofenac sodium gel 1% was 5- to 17-fold lower than with oral diclofenac. Systemic effects with topical diclofenac were less pronounced.
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              Skin penetration and tissue permeation after topical administration of diclofenac.

              Topical delivery of drugs is an alternative to oral administration, often with similar efficacy but potentially a more favorable tolerability profile. However, topical formulations need to be able to penetrate the skin and permeate to the target areas in quantities sufficient to exert a therapeutic effect. Many factors can affect this process, including the physicochemical properties of the drug, the formulation used, and the site and mode of application. It is believed that measurement of drug concentrations at the sites of action may be an indicator of their likely efficacy. This review addresses these issues, with reference to topically administered diclofenac in osteoarthritis.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                JPR
                jpainres
                Journal of Pain Research
                Dove
                1178-7090
                02 July 2020
                2020
                : 13
                : 1621-1627
                Affiliations
                [1 ]Department of Chemistry, Rutgers University , Newark, NJ 07102, USA
                [2 ]Charles River Laboratories Edinburgh Ltd ., Tranent, East Lothian, UK
                [3 ]GSK Consumer Healthcare S.A ., Nyon 1 1260, Switzerland
                Author notes
                Correspondence: Mila Boncheva Bettex GSK Consumer Healthcare S.A ., Route de l’Etraz 2, Case Postale 1279, Nyon1260, SwitzerlandTel +41 79 700 9281 Email mila.x.boncheva-bettex@gsk.com
                Author information
                http://orcid.org/0000-0001-6972-8508
                http://orcid.org/0000-0001-6677-6627
                http://orcid.org/0000-0001-5849-7927
                Article
                253069
                10.2147/JPR.S253069
                7342390
                32753939
                a4aaaaee-4d16-410d-8ecc-a25081e6bfa1
                © 2020 Zhang et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 13 April 2020
                : 09 June 2020
                Page count
                Figures: 5, Tables: 1, References: 19, Pages: 7
                Categories
                Original Research

                Anesthesiology & Pain management
                diclofenac,drug permeation,epidermal reservoir,raman microscopy,skin depot,topical pain relief

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