The skin penetration of 10 nonsteroidal antiinflammatory drugs (NSAIDs) was investigated after application in the lipophilic vehicle light mineral oil. The skin permeabilities and maximum fluxes, which were calculated from the concentration decreases of the applied solutions in the steady state phases, were correlated with physicochemical parameters, mainly the vehicle solubilities and the partition coefficients of the model drugs according to the Fickian diffusion laws. The objective of the study was to characterize the barrier function of the stratum corneum and the viable epidermis and to predict their influences on the skin permeabilities and the maximum fluxes of the NSAIDs by model equations. The permeability of the human skin for NSAIDs applied in a lipophilic vehicle is a function of their hydrophilicity, while the maximum flux is primarily dependent on their vehicle solubilities. The viable epidermis was found to represent the decisive resistance to the drug transport.

The statistical distribution of the skin permeability of ten non‐steroidal anti‐inflammatory drugs (NSAIDs), previously determined in‐vivo in 24 healthy volunteers, was investigated. Graphical evaluation using histograms and quantile diagrams of the residuals as well as the calculated results obtained from the Kolmogoroff‐Smirnow tests and analyses of variance, suggest the log‐normal distribution to be the most suitable approximation.

The maximum cutaneous fluxes of 12 nonsteroidal anti-inflammatory drugs (NSAIDs), determined in a preceding study from the lipophilic vehicle light mineral oil in vivo on 24 healthy volunteers, were related to data concerning their intrinsic activities. From the multiplication of the relative intrinsic activities with the relative maximum fluxes, both related to indometacin (CAS 53-86-1) as standard, the percutaneous activities result as parameters for the prediction of the efficacy of cutaneous preparations with NSAIDs. According to the results of the calculations, the percutaneous activities of ibuprofen (CAS 15687-27-1) and nabumetone (CAS 42924-53-8) from lipophilic vehicles are remarkable because of their very high maximum fluxes. NSAIDs with still high percutaneous activities are ketoprofen (CAS 22071-15-4), naproxen (CAS 22204-53-1), piroxicam (CAS 36322-90-4) and diclofenac (CAS 15307-86-5). In contrast, the systemically highly effective NSAIDs indometacin and acemetacin (CAS 53164-05-9) show rather low percutaneous activities, when applied in lipophilic vehicles. Especially nabumeton and also tenoxicam (CAS 59804-37-4), both not yet commercially used cutaneously, can be recommended for lipophilic skin preparations.