Favourable dermal penetration of diclofenac after administration to the skin using a novel spray gel formulation

Abstract

AimsThe study was designed to evaluate the relative bioavailability of diclofenac in plasma, subcutaneous adipose and skeletal muscle tissue after repeated topical administration using MIKA Diclofenac Spray Gel (4%), a novel formulation, and after oral dosing using VOLTAREN " 50 mg enteric coated tablets. MethodsDiclofenac (48 mg) was administered topically three times daily for 3 days onto a defined area of the thigh of 12 healthy males. After a 14-day wash out period, subjects were orally treated with 50 mg diclofenac three times daily for 3 days. In vivo microdialysis in subcutaneous and muscle tissues was per formed immediately after the final doses from both treatments on day 4, and 48 h later. Plasma samples were taken simultaneously. ResultsThe relative bioavailability of diclofenac in subcutaneous adipose and skeletal muscle tissue was substantially higher after topical compared with oral dosing (324% and 209%, respectively) whereas relative plasma bioavailability was 50-fold lower. Plasma C max values were approximately 250-fold lower after topical compared with oral drug administration (i.e. median values = 4.89 ng mL -1 ; 95% CI: 3.37-7.68 and 1240 ng mL -1 ; 95% CI: 787-1389 ng mL -1 ). Both treatments were well tolerated. ConclusionsOwing to its favourable penetration characteristics and low systemic availability, MIKA Diclofenac Spray Gel 4% is a rational alternative to oral diclofenac formulations for the treatment of inflammatory soft tissue conditions.

Microdialysis Sampling for Investigations of Bioavailability and Bioequivalence of Topically Administered Drugs: Current State and Future Perspectives

“…Also felbinac (transdermal therapeutic system) and diclofenac (spray gel), two topical drugs for treatment of muscle inflammation, have been examined using MD. Based on the high drug concentrations found in the skin and subcutaneous tissues, respectively, both administration modalities were shown to be possible alternatives to orally administered nonsteroidal anti-inflammatory drugs for superficial muscle inflammation [91,117] . Ketoprofen penetration kinetics following application as a transdermal therapeutic system (with the target being intra-articular inflammation) has been measured in the skin as well as in the knee joint by MD.…”

Assessment of Topical Bioequivalence Using Dermal Microdialysis and Tape Stripping Methods

“…4 The mean oxytetracycline HCl profiles in the dermis for the test and the reference in 10 healthy volunteers (Microdialysis results). (24)(25)(26)(27)(28)(29)(30)(31). However, topical BE studies using MD in humans are limited (32)(33)(34)(35)(36).…”

Topical and Regional Treatment for Osteoarthritis

“…The skin appears to act as a 'reservoir' from which the drug is distributed to deeper tissues (30). Only 3-7% of the applied dose is systemically absorbed (29) and mean plasma concentrations are typically 5% or less of the level reached following oral administration (31,32). Low systemic absorption is evidenced further by the lack of symptom relief in other joints distant to the site of application (33).…”