Optimization of bioavailability of topical steroids: penetration enhancers under occlusion.
The occluded vasoconstrictor assay was used to assess the effect of penetration enhancers on the topical bioavailability of a representative steroid, betamethasone 17-benzoate, with dimethylisosorbide (DMI) as a reference solvent. In the initial test, only N-methyl-2-pyrrolidone (NMP) increased the steroid bioavailability; acetone, dimethylformamide (DMF), 2-pyrrolidone (2-P), and 1-ethyl-2-pyrrolidone (EP) were equal to DMI, while propylene glycol (PG) and N,N-diethyl-m-toluamide (DEET) were poorer. Reocclusion showed that NMP and acetone established superior stratum corneum reservoirs; DMF, 2-P, EP, and PG were as effective as DMI but DEET was less effective. It was concluded that occlusive hydration and lack of thermodynamic control may have obscured the enhancing abilities of the solvents, 2-P, NMP, EP, DMF, and DEET induced erythema in some volunteers, although this was usually short-lived.
D000096:Acetone / Q000494:pharmacology; D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D001623:Betamethasone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D001682:Biological Availability; D004126:Dimethylformamide / Q000494:pharmacology; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007547:Isosorbide / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011760:Pyrrolidinones / Q000494:pharmacology; D012996:Solutions; D012997:Solvents / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
D011760:Pyrrolidinones; D012996:Solutions; D012997:Solvents; D000096:Acetone; D004126:Dimethylformamide; C015706:betamethasone benzoate; D001623:Betamethasone; C040079:2,5-dimethylisosorbide; D007547:Isosorbide