EFFECT OF FORMULATION ADDITIVES UPON THE INTRANASAL BIOAVAILABILITY OF A PEPTIDE DRUG - TETRACOSACTIDE (ACTH(1-24))

Nasal absorption of tetracosactide (ACTH(1-24); Synacthen) was evaluat ed in anesthetized rats and compared to intravenous and intramuscular (i.m.) administration. The effect of formulation additives on tetracos actide bioavailability was studied following modification of nasal sal ine solution. Poloxamer 407 (Pluronic F-127) was used as a vehicle for drug sustained release, whereas sodium glycocholate and bacitracin we re used as enhancers. Tetracosactide plasma levels were monitored with radioimmunoassay. Nasal bioavailability was low (4.4%) compared to i. m. (24%). Poloxamer 407 addition did not improve drug kinetics profile s and showed a nonsignificant decrease in bioavailability (4%). On the other hand, both enhancers effectively increased tetracosactide nasal absorption. The sodium glycocholate effect was very fast (T-max = 5 m in), but did not last long. Moreover, absorption was increased threefo ld compared to the simple formulation. On the other hand, maximum tetr acosactide levels in plasma were reached after 15 min for the formulat ion containing bacitracin as enhancer, and tetracosactide bioavailabil ity was strongly increased, to 24%, i.e., as much as after an i.m. inj ection.