Characterisation of aerosols from solution-based pressurised metered dose inhalers (pMDIs) when delivered by PreciseInhale®
Wachirun Terakosolphan1, Maria Malmlöf 2, David Lewis3 & Ben Forbes1
1 Institute of Pharmaceutical Sciences, King’s College London, SE1 9NH, UK
2 Inhalation Sciences, Hälsovägen 7, Stockholm, Sweden
3 Chiesi Limited, Chippenham, Wiltshire, SN14 0AB, UK
Glycerol is incorporated in some solution-based pressurised metered dose inhalers (pMDIs) to modify the particle size distribution of emitted aerosols, thereby controlling regional deposition in the lungs. However, evidence is emerging that glycerol may unintentionally influence the dissolution, transport and metabolism of beclomethasone dipropionate (BDP) after particle deposition. To investigate these effects, solution-based metered dose BDP inhalers were formulated to be pharmaceutically-equivalent, except for the presence or absence of glycerol. The aim of this study was to characterise the aerosols produced by BDP pMDI when delivered via the PreciseInhale® apparatus in preparation for in vivo studies in rats. The particles were characterised in terms of their mass median aerosol diameter (MMAD) and morphology. The emitted aerosols from four BDP pMDIs were characterised; two licensed non-bioequivalent inhalers (Qvar and Clenil) and two pharmaceutically equivalent in-house inhalers (glycerol-free and glycerol-containing inhalers, previously designated as red and blue formulations, respectively). The MMAD produced by each inhaler were equivalent when delivered via Precise Inhale® compared to when measured directly using a Next Generation Impactor. Electron microscopy showed that the respirable solid particles generated by Qvar were spherical, porous, 2 to 3-fold smaller than the ~3.7 μm particles produced by Clenil, with more irregular shape and ruptured surfaces. In accordance with their design, the red and blue pMDI generated particles of equivalent size, approximately ~2.3 μm. In conclusion, the BDP pMDI aerosols administered via the PreciseInhale® aerosol system were indistinguishable from when they underwent standard in vitro testing and are suitable for investigating the effects of glycerol in vivo.