Flixotide™‐pressurized metered‐dose inhalers loaded with [18F]fluticasone propionate particles for drug deposition studies in humans with PET–formulation and analysis

Fluticasone propionate (FP) is a potent anti‐inflammatory synthetic steroid, used for the treatment of asthma. Flixotide? is a formulated pressurized metered‐dose inhaler (pMDI) that contains small‐micronized FP particles in a blend of CFC propellants. Our objective was to develop a radiotracer method for accurately measuring the regional deposition of FP within the human lung using positron emission tomography (PET), which would be of important clinical interest. Flixotide? pMDIs were used to prepare ¹⁸F]FP pMDIs labeled isotopically with the positron emitter, fluorine‐18 (t_1/2=109.7 min). FP particles from Flixotide? pMDIs were mixed with ¹⁸F]FP formulated into a pMDI and sonicated at room temperature. The drug delivery of ¹⁸F]FP pMDI (250 μg of FP per actuation dose) was assessed for particle size distribution and dose uniformity. The distributions of FP and ¹⁸F]FP across particle size in such preparations were measured with an Andersen cascade impactor. This procedure was shown to provide an emitted dose from a ¹⁸F]FP pMDI of 246±19 μg/per metered dose. The particle size distribution as measured by mass median aerodynamic diameter (MMAD) (The mass median aerodynamic diameter (MMAD) and the geometric standard deviation (GSD) for each distribution were calculated. MMAD is defined as the aerodynamic diameter around which the mass of particles is equally distributed and the GSD is a measure of the dispersion of these particle diameters around the MMAD) from a commercial Flixotide? pMDI was 2.6±0.2 μm and agreed well with that from an ¹⁸F]FP pMDI (2.8±0.1 μm). The MMAD and geometric standard deviation (GSD) of newly formulated ¹⁸F]FP pMDIs were unaffected by the formulation procedure. ¹⁸F]FP was distributed with good uniformity with respect to the mass of FP for particles greater than 0.43 μm. Hence, the radiolabeled pMDI is a suitable source of radiotracer for the regional measurement of lung deposition for inhaled FP in human subjects with PET. Copyright © 2003 John Wiley & Sons, Ltd.