ABSORPTION OF TRANSDERMALLY DELIVERED KETOROLAC ACID IN HUMANS

Transdermal delivery of ketorolac acid, a potent analgesic, through hu man skin in vitro and in vivo was evaluated. The following three trans dermal solutions were selected to study the in vitro skin permeation r ate of ketorolac acid: formulation A, isopropyl alcohol:water: isoprop yl myristate (IPA/water/IPM; 11:7:1); formulation B, ethanol: propylen e glycol:isopropyl myristate (ET/PG/IPM; 11:7:2); and formulation C, I PM/capmul (glycelyl mono- and dicaprylate; Monoctanoin). The permeatio n of ketorolac acid through cadaver skin from a saturated drug solutio n was evaluated at 32 degrees C with a modified Franz diffusion cell. The in vitro skin fluxes were 180, 177, and 14 mu g/cm(2)/h for fomula tions A, B, and C, respectively. The systemic bioavailability of ketor olac acid from three transdermal formulations was evaluated in nine he althy subjects in a randomized three-way crossover fashion. Hill Top c hambers were used as prototype dermal delivery devices to load the dru g solution, This procedure was followed by the immediate application o f devices to human subjects for 24 h. Blood samples were collected at various time intervals up to 48 h, and the samples were assayed by HPL C. The basic pharmacokinetic parameters were derived from the drug pla sma concentration versus time plot. The maximum drug plasma concentrat ions were 1.265, 0.696, and 0.092 mu g/mL for formulations A, B, and C , respectively. Formulation A provided the highest in vitro and in viv o transdermal delivery rate among the three formulations studied. An e xcellent correlation between the in vitro steady-state skin flux and t he area under the curve of in vivo plasma drug concentration versus ti me was observed for all the three formulations.