Absorption through human skin of ibuprofen and flurbiprofen; effect of dose variation, deposited drug films, occlusion and the penetration enhancer N-methyl-2-pyrrolidone.
The penetration of ibuprofen and flurbiprofen, non-steroidal anti-inflammatory agents, was investigated from drug films deposited by acetone evaporation on cadaver skin in an open cell 'in-vivo mimic' design. Increased dosage did not produce a proportional increase in the permeation and maximizing the skin-drug contact did not increase penetration: both factors indicate that absorption from deposited drug films was dissolution rate-limited. Occlusion of the skin did not increase the dissolution rate of the deposited drug film, but did elevate the penetration of drug already present within the skin at the time of occlusion. The diffusion coefficients for both drugs were calculated by two methods, yielding 1.8 +/- 1.3 X 10(-11) cm2 s-1 and 1.0 +/- 0.56 X 10(-11) cm2 s-1 for ibuprofen and 1.9 +/- 0.59 X 10(-11) cm2 s-1 and 0.77 +/- 0.23 X 10(-11) cm2 s-1 for flurbiprofen. Increasing the acetone-skin contact time from 2 min to 2 h did not significantly alter the permeability of the skin. Absorption of flurbiprofen was similar from 10 and 100% saturated aqueous solutions, suggesting that the skin has a limited capacity for flurbiprofen transport beyond which further increase in drug penetration may be difficult. N-Methyl-2-pyrrolidone enhanced the penetration flux of ibuprofen sixteenfold and flurbiprofen, over threefold. The 'in-vivo mimic' design for permeation experiments has thus proved to be useful for evaluating the kinetics of topical therapy and the mechanism of action of potential penetration enhancers.
Akhter
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D000096:Acetone; D000368:Aged; D001241:Aspirin / Q000378:metabolism; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D005260:Female; D005480:Flurbiprofen / Q000378:metabolism*; D006801:Humans; D007052:Ibuprofen / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D010539:Permeability; D011422:Propionates / Q000378:metabolism*; D011760:Pyrrolidinones / Q000494:pharmacology*; D012869:Skin Absorption
D011422:Propionates; D011760:Pyrrolidinones; D000096:Acetone; D005480:Flurbiprofen; C038678:N-methylpyrrolidone; D001241:Aspirin; D007052:Ibuprofen