Abstract
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, Kp; lag time, TL, 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 Kp 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 ∼0% ionization (Kp=3.5cm/h) and ketoprofen had the highest flux (J=16 µg/h·cm2) of the NSAIDs assayed. Ketorolac would provide the plasma concentrations at steady state that would be nearest to the therapeutic concentration (Ct/Css=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.
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