Pradal J, et al. - Given the dependency of the therapeutic effect of topical nonsteroidal anti-inflammatory drugs (NSAIDs) on the drug’s ability to penetrate and permeate the skin and subsequently inhibit cyclo-oxygenase (COX) isoforms responsible for pain and inflammation, researchers here analyzed the skin absorption of representative commercially available topical diclofenac- and ibuprofen-based formulations in addition to published potency values with the aim to assess formulations with superior anti-inflammatory activity. Twelve commercially available topical NSAIDs (6 diclofenac-based and 6 ibuprofen-based) were evaluated in vitro for their cumulative absorption and flux profiles using human skin in static Franz diffusion cells. They applied each formulation as a single dose. They calculated a modified index of topical anti-inflammatory activity (mITAA) using in vitro permeation parameters and published COX-2 inhibition values. The calculated index suggested superiority of diclofenac in terms of anti-inflammatory activity. Differences in absorption and thus in anti-inflammatory activity seemed to be attributable to the differences beyond drug concentration, including excipients, drug salt form, and dosage form. For anti-inflammatory activity, they identified both absorption and COX-2 inhibition potency as important, however, their priority depends upon the products being compared—with the same NSAID, absorption determines superiority; with different NSAIDs, superiority is decided by the balance between absorption and COX-2 potency. They emphasize considering these findings when making a choice concerning a topical NSAID for treating patient pain and inflammation.