Aerodynamic Characterization of Inhaler Formulations

DD and FPD were determined by using the sampling apparatus and procedures described in European Pharmacopoeia 8.0; for each flow rate evaluated, 4 L of air was drawn through the inhaler.^{(24 )}Salmeterol and Fluticasone propionate collected in the sampling apparatus were analyzed by high-performance liquid chromatography method with UV detection at 280 nm. The chromatographic separations were carried out at 40°C on an Inertsil ODS-3 C18, 3 μm, 4.0 × 150 mm analytical column (GL Sciences) using 100 μL injection volume. The mobile phase, methanol:0.02 M phosphate buffer, pH 6.2 (25:75), was delivered at a flow rate 1 mL/mL. The samples were dissolved in water:acetonitrile 50:50 (v/v) and sample volume was 50 mL for DD samples and varied from 10 to 65 mL for FPD samples. The quantitation limit of the method for Salmeterol was 0.03 μg/mL and for Fluticasone Propionate, 0.1 μg/mL. The relative standard deviation of the peak areas varied not more than 2% during analysis.
For assessments of DD, a total of 36 devices were tested (three devices for each flow rate and strength/batch). Ten doses were measured for each inhaler, and the mean DDs were calculated.
FPD was defined as the amount of particles with an aerodynamic diameter ≤5 μm. FPD was determined using Next Generation Impactor (NGI, apparatus E).^{(24 )} The cutoff points for impactor stages were calculated in relationship to the used flow rates according to European Pharmacopoeia 8.0,^{(24 )} and FPD was derived from the data. For each FPD analysis, 10 doses were discharged into the NGI.