AbstractPurposeTopical nonsteroidal anti‐inflammatory drug formulations are used commonly to treat musculoskeletal pain and inflammation. Drug properties and formulation composition are the primary determinants of the transdermal drug delivery rate. The ex vivo transdermal flux through human skin of three topical diclofenac formulations was compared.MethodsThe formulations tested were hydrogel 1% diclofenac sodium and two emulsion gels (1.16%/2.32% diclofenac diethylamine, equivalent to 1%/2% diclofenac sodium). Human abdominal skin obtained during unrelated surgical procedures was stored at −20 °C until use. Skin specimens were thawed, prepared and placed in Franz diffusion cells (stratum corneum facing donor cell). The test formulation (~200 mg) was applied to the donor cell skin surface, and the receptor compartment was periodically sampled over 48 hours. The drug concentration in the receptor medium was determined by a validated HPLC method. Raman spectral imaging was performed to visualize the location and distribution of diclofenac.ResultsAfter 5 hours, the cumulative amount of hydrogel diclofenac transiting the skin was about 10 times that of the emulsion gel 1.16% (P=0.0004) and about twice that of the emulsion gel 2.32% (P=0.022). Similar results were seen after 9 hours. Raman spectroscopy showed that the hydrogel formulation was a homogeneous mixture of its various components, including diclofenac. The emulsion gels were non‐homogeneous, with diclofenac in close proximity to the lipophilic (paraffin) phase.ConclusionsThe transdermal transit of diclofenac from the hydrogel demonstrated a faster onset and a greater absorption rate than either emulsion gel formulation, suggesting that the hydrogel formulation may have a faster onset of action in underlying tissues vs. the emulsion gel products.