In vitrovalidation of the use of a spacer with an extrafine beclomethasone/formoterol formulation

Introduction - Lung deposition of aerosolized drugs is dependent on inhalation technique, device and formulation. Valved holding chambers (VHC) are accessories sometimes needed for proper drug distribution with pMDIs (pressurized metered-dose inhaler). However because changes to devices can be associated with negative outcomes, characterization of the resulting aerosol particles is essential. The performance of an extrafine formulation (Innovair, Chiesi) of a β2 adrenergic agonist( Formoterol/FF) combined with a corticosteroid (Beclomethasone/BDP) via pMDI was characterized in vitro with or without VHC (Tips-haler, Protec9Som). Methods - Particle size distributions were measured using a cascade impactor(Next Generation Impactor, Copley Scientific) at 30L/min. All components were tested for drug deposition. Samples were HPLC analyzed for the simultaneous detection of BDP and FF. Values are reported as means±standard deviation. Results - Doses delivered (DD) were equivalent for the pMDI used alone or with VHC (FF: 4.23±0.4µg pMDI/4.3±0.19µg pMDI+VHC; BDP: 71.94±5.98µg pMDI/73.73±5.44µg pMDI+VHC). Drug ratio (BDP/FF) were found to be unchanged (17.04±1.05 pMDI; 17.14±0.75 pMDI+VHC; 16.7 nominal dose). A 10% increase of the fine particle fraction (FPF) was found for both drugs when the VHC was used (FF: 39.93±4.04 pMDI/52.11±6.73 pMDI+VHC; BDP: 45.59±4.08 pMDI/57.08±8.1 pMDI+VHC). Conclusion - MDIs emitting fine particles provide higher lung deposition and improved clinical benefits. In vitro characterization of MDIs used with VHC is a necessary step towards ensuring that those advantages are preserved. We showed that the VHC used here with an extrafine formulation maintains DD and increases FPF.