Comparison of the fine particle fraction of fluticasone propionate/formoterol fumarate combination with other combination products

Background : A combination of the inhaled corticosteroid, fluticasone propionate, and the long-acting β2-agonist, formoterol fumarate has been developed in an aerosol inhaler (FLUT/FORM). As changes in flow rate have been shown to affect the in-vitro performance of inhalers, which could compromise in-vivo performance, this study evaluated the effect of flow rate on fine particle fraction (FPF) and dose (FPD) of FLUT/FORM and three available combination products. Methods : Dose strengths used to deliver comparable treatment doses (FLUT/FORM, 250/10µg; beclomethasone/formoterol (BDP/FORM) pMDI, 200/12g; fluticasone/salmeterol (FLUT/SAL) DPI, 250/50µg; budesonide/formoterol (BUD/FORM) DPI, 400/12µg) were compared. Aerodynamic particle size distribution was determined by Andersen Cascade Impaction at 28.3L/min and 60L/min flow rates with a cut-off diameter of 5.0 µM and was calculated as % of label claim. Results : FLUT/FORM provided a consistent and high FPF of approximately 40% for each component, with less than a 10% relative difference in the FPD emitted between flow rates. FLUT/FORM provided the highest FPF at both flow rates with BUD/FORM and FLUT/SAL delivering a FPF of less than 20% at 28.3L/min. The FPD of all three comparator products evaluated were affected by increases in flow rate from 28.3L/min to 60L/min, with BUD/FORM having a ∼5 fold increase in FPD between flow rates and BDP/FORM showing a 50% difference. Conclusion: The data confirm that FLUT/FORM emits a high FPF of approximately 40%. These data also demonstrate that FLUT/FORM has a higher FPF, that is less affected by changes in flow rate, than other combination products assessed.