Skin penetration and tissue permeation after topical administration of diclofenac

Abstract

Objective: 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.

Methods: Articles relevant to this review were identified after a systematic search of Medline and Embase, using the key words “diclofenac”, "topical administration" and “osteoarthritis” in the search strategy.

Results: The sparse data available indicate that topical diclofenac can penetrate and permeate to deeper tissues, with a lower plasma to tissue ratio than oral diclofenac. The tissue diclofenac levels after topical delivery are sustained over time (at least several hours). However, there is not enough data to establish how diclofenac levels in the joint compare with IC₅₀ levels (50% of the maximum inhibition of prostaglandin synthesis) established following oral administration.

Conclusions: After topical application, diclofenac can penetrate the skin and permeate to deeper tissues, where it reaches a concentration that appears to be sufficient to exert a therapeutic effect. More robust methods are required for in vivo characterization to better estimate the clinical efficacy of topically applied drugs.

Keywords:

• Concentration
• joint
• skin penetration
• tissue permeation
• topical diclofenac

Transparency

Declaration of funding

There is no sponsorship or funding to declare from GlaxoSmithKline Consumer Healthcare or otherwise.

Author contributions: M.H. and M.B. were involved in the conception of the review, analysis and interpretation of the data, drafting of the manuscript and revising it critically for intellectual content, and final approval of the version to be published. Both authors are accountable for all aspects of the work.

Declaration of financial/other relationships

M.H. and M.B. have disclosed that they are salaried employees of GlaxoSmithKline Consumer Healthcare, who also paid for the services of the medical writer, Deborah Nock.

Acknowledgements

Thanks are given to Beata Coffey, Information Specialist at the Royal Society of Medicine Library, for her systematic review of the literature. The manuscript was drafted and edited by a professional medical writer, Deborah Nock (Medical WriteAway, Norwich, UK).