Mei-Chang Kuo

A Comparison of the Pulmonary Bioavailability of Powder and Liquid Aerosol Formulations of Salmon Calcitonin

PurposeTo compare the pulmonary pharmacokinetics and relative bioavailability of salmon calcitonin delivered as aqueous droplets, pHxa06.6 and pHxa04.8 with that of a spray dried powder in healthy volunteers.MethodsSpray dried powders (1.6xa0μm [GSD 2.1]) containing 5% by wt. sCal, 6.25% human serum albumin, 73.55% mannitol and 15% citric acid/sodium citrate were prepared using a Buchi model 190 spray drier. Aqueous solutions were prepared by dissolving the spray dried powder at a sCal concentration of 1.25xa0mg/ml, pH was adjusted using 21xa0mM sodium hydroxide. Aerosols were delivered as part of a 4 way cross-over study to 16 healthy volunteers. The Nektar pulmonary delivery device was used to deliver the dry powder aerosol. A Salter nebulizer controlled by a Rosenthal dosimeter was used to deliver the aqueous aerosols. Miacalcin™ injection was used as the subcutaneous control. Dose delivered to the lung was estimated by gamma scintigraphy. Plasma concentrations of sCal were measured using a radioimmunoassay.ResultsAerosol size distributions were matched, 3.3xa0μm MMAD and ∼2.2 GSD. Inhaled flow rates were similar, although not equal, 5.8 and ∼9.8xa0l/min respectively for dry powder and liquid inhalations. Lung doses of sCal ranged from 53 to 88xa0μgm, peripheral lung doses from 25 to 51xa0μgm. Pharmacokinetic profiles and lung bioavailability relative to subcutaneous injection for all formulations were similar (not statistically significantly different pu2009>u20090.05), relative lung bioavailability ranged from 11% to 18%, estimates of relative bioavailability based on peripheral lung dose ranged from 20% to 33%.ConclusionThe study showed no difference in pharmacokinetic profiles between the various aerosol dosage forms. pH of the aqueous solutions did not affect kinetics or relative bioavailability.