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

AIMS: The 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. METHODS: Diclofenac (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 performed immediately after the final doses from both treatments on day 4, and 48 h later. Plasma samples were taken simultaneously. RESULTS: The 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. CONCLUSIONS: Owing 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.