BIOPHARMACEUTICAL EVALUATION OF TRANSNASAL, SUBLINGUAL, AND BUCCAL DISK DOSAGE FORMS OF BUTORPHANOL

A series of three-way crossover randomized studies were conducted to e valuate the absolute bioavailability of butorphanol, a potent agonist- antagonist analgesic, from transnasal, sublingual, and buccal disk for mulations in order to identify a practical alternative to oral adminis tration. In each study, healthy male volunteers received 2 mg doses of butorphanol tartrate intravenously and either transnasally, sublingua lly or buccally. Serial blood samples were collected over 12 h and but orphanol plasma concentrations were determined by radioimmunoassay. Th e plasma concentration data were subjected to non-compartmental pharma cokinetic analysis. The elimination half-life of butorphanol was about 3-5 h and was independent of the route of administration. Absorption of butorphanol following transnasal administration was faster than tha t observed following sublingual or buccal administration. Mean absolut e bioavailabilities of sublingual tablet and buccal disk formulation w ere only 19 per cent and 29 per cent, respectively, but for transnasal administration the value rose significantly, to 70 per cent. Based on the results of these studies, transnasal dosage form of butorphanol w as selected for further clinical trials of treatment of moderate to se vere pain.