Assessment of Potential Mouth/Throat Deposition and Lung Delivery of Suspension- and Solution-Formulated Inhaled Corticosteroid (ICS) Formulations Delivered by Pressurized Metered-Dose Inhaler (pMDI) without and with Valved Holding Chamber (VHC) Using an Anatomic Adult Upper Airway

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Assessment of Potential Mouth/Throat Deposition and Lung Delivery of Suspension- and Solution-Formulated Inhaled Corticosteroid (ICS) Formulations Delivered by Pressurized Metered-Dose Inhaler (pMDI) without and with Valved Holding Chamber (VHC) Using an Anatomic Adult Upper Airway

Jason A Suggett1, Mark W Nagel1 & Jolyon P Mitchell2

1Trudell Medical international, 725 Third Street, London, Ontario, N5V 5G4, Canada

2Jolyon Mitchell Inhaler Consulting Services Inc., 1154 St. Anthony Road, London, Ontario, N6H 2R1, Canada

Summary

This pilot study explored how insertion of a representative VHC in the pathway between pMDI and mouth might affect transfer of particles from inhaler mouthpiece to the airways of the lungs. The behaviour of a conventional suspension-formulated ICS (Flovent-125*; fluticasone propionate (FP)) with mass median aerodynamic diameter (MMAD) close to 2.4-mm was compared with that of a solution-formulated ICS (Qvar-100*; beclomethasone dipropionate (BDP)) producing ultrafine particles with MMAD close to 1.1-mm.  The inhaler-on-test was actuated into the mouth of an adult tidal-breathing anatomically correct oropharyngeal airway.  A filter located distal to the airway at the approximate position of the carina provided measures of potential lung deposition. When the VHC was absent, medication (62.1±5.7% FP and 29.4±5.9% BDP, based on label claim mass/actuation (%LC)) deposited in the oropharyngeal passageway. Oropharyngeal deposition was greatly reduced (7.2±0.8%LC for FP and 3.2±0.1%LC for BDP) when the VHC was present. As expected, the finer aerodynamic particle size distribution of ultrafine BDP particles (35.7 ± 6.4%LC) resulted in greater penetration to the filter compared with the coarser FP particles (7.1±1.2%LC) when the VHC was absent. A further increase in filter-collected mass was observed for both formulations (27.3±3.0%LC for FP and 49.3±2.3%LC for BDP) when the VHC was used with the pMDI.  These findings confirm potential benefits of finer solution over suspension based HFA formulations in terms of reduced oropharyngeal deposition and increased availability to the lungs, and also demonstrate the value of a VHC by reducing oropharyngeal deposition in either formulation type.