Impact of droplet evaporation rate on resulting in vitro performance parameters of pressurized metered dose inhalers

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Abstract

Pressurized metered dose inhalers (pMDIs) are widely used for the treatment of pulmonary diseases. The overall efficiency of pMDI drug delivery may be defined by in vitro parameters such as the amount of drug that deposits on the model throat and the proportion of the emitted dose that has particles that are sufficiently small to deposit in the lung (i.e., fine particle fraction, FPF). The study presented examines product performance of ten solution pMDI formulations containing a variety of cosolvents with diverse chemical characteristics by cascade impaction with three inlets (USP induction port, Alberta Idealized Throat, and a large volume chamber). Through the data generated in support of this study, it was demonstrated that throat deposition, cascade impactor deposition, FPF, and mass median aerodynamic diameter of solution pMDIs depend on the concentration and vapor pressure of the cosolvent, and the selection of model throat. Theoretical droplet lifetimes were calculated for each formulation using a discrete two-stage evaporation process model and it was determined that the droplet lifetime is highly correlated to throat deposition and FPF indicating that evaporation kinetics significantly influences pMDI drug delivery.

Graphical abstract

Discrete two-stage evaporation process for droplets from solution pMDIs with three of the ten different formulations evaluated (orange/top: 0.3% drug in HFA-134a; green/middle: 0.3% drug with 8% ethanol (EtOH) in HFA-134a; and blue/bottom: 0.3% drug with 20% ethanol in HFA-134a). This dynamic droplet evolution from initial droplet to residual particles can have a significant impact on throat deposition and fine particle fraction. The initial droplets depicted represent the mass median droplet size; evaporation times, relative throat deposition, and relative fine particle fraction are determined from experimental data, presented herein.

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