A comparative study of the transdermal penetration of a series of nonsteroidal antiinflammatory drugs

The transdermal absorption of a series of nonsteroidal antiinflammatory drugs (NSAIDs): indomethacin, ketoprofen, diclofenac, piroxicam, tenoxicam, ketorolac, and aceclofenac) was studied in vitro with human skin. The purpose of the study was to determine the permeation parameters (permeability rate constant, K-p; lag time, T-L, and flux, J) as measures of the intrinsic transdermal permeabilities of these drugs to predict their potential for formulation in a transdermal therapeutic system (TTS). A linear correlation was established between the intrinsic log K-p values and the intrinsic partition coefficients (r = 0.863, p = 0.012, n = 7). Diclofenac had the highest value of in vitro transdermal penetration at similar to 0% ionization (K-p = 3.5 cm/h) and ketoprofen had the highest flux (J = 16 mu g/h.cm(2)) of the NSAIDs assayed. Ketorolac would provide the plasma concentrations at steady state that would be nearest to the therapeutic concentration (C-t/C-ss = 26). Also, considering the whole permeation profile in vitro, ketorolac would be the most suitable candidate of the series studied to be formulated as a TTS.