REGIONAL LUNG DEPOSITION OF NEBULIZED LIPOSOME-ENCAPSULATED CIPROFLOXACIN

Liposome-encapsulated ciprofloxacin (22.2 mg ciprofloxacin/ml) was neb ulized in 25 nebulizers (five nebulizers from each of five nebulizer t ypes). The aerosol was inhaled by a breath simulator (square wave patt ern, 0.75 l tidal volume, 0.3 l/s inhalation flow rate) and inhaled dr oplet sizes were characterized using in-line phase Doppler anemometry. Filter collection combined with centrifugation, UV spectrophotometry and measurement of original entrapment efficiency using C-14-radiolabe lled ciprofloxacin was used to determine % encapsulation in the inhale d aerosol. Cascade impaction combined with chemical assay showed that encapsulated and free ciprofloxacin were homogeneously distributed amo ng the inhaled droplet sizes. Combination of the above measurements wi th a mathematical lung deposition model allowed prediction of the amou nts of encapsulated ciprofloxacin depositing in the tracheo-bronchial, alveolar and extrathoracic regions of the respiratory tract. The nebu lizer types (Pari LC STAR, Pari LC+, Medix Sonix 2000, Hudson T-Updraf t II, DeVilbiss Permaneb) differed by up to a factor of 30 in the amou nt of encapsulated ciprofloxacin depositing in the different regions o f the lung (e.g. lung deposition of entrapped ciprofloxacin varied fro m 0.7% to 18.1% of total ciprofloxacin dose placed in the nebulizer). Much of this dramatic difference was due to the differing amounts of l iposomal disruption, which varied among the different nebulizer types from no measurable disruption to nearly complete disruption. (C) 1998 Elsevier Science B.V. All rights reserved.