Importance of the Tongue as an Impactor for Orally Inhaled Aerosols from a Pressurised Metered Dose inhaler (pMDI) With and Without a Valved Holding Chamber (VHC)

• Positioning of the tongue during inhaler medication delivery is something that is not thought about by either users or caregivers.
• The tongue acts as an impaction surface for the high initial velocity of the expanding  plume emitted from a pMDI.
• An alternative is to use the inhaler with a VHC that by virtue of its internal volume, allows the plume to expand and slow its forward velocity before being inhaled.

To compare the amount of oropharyngeal impaction by using a series of model adult oropharyngeal cavities (OCs) in which only the tongue size was progressively reduced.

• Measurements undertaken (n = 5 replicates at each condition) using pMDIs delivering a nominal dose/actuation of 90 μg salbutamol ex actuator mouthpiece and assayed drug mass by a validated HPLC method.
• We developed four sintered nylon adult oropharyngeal casts (Figure 1) based on the ADAM-III internal geometry by a 3-D printing process (Materialise, Leuven, Belgium).
• We connected the exit from the model on test directly to an abbreviated Andersen cascade impactor to measure total mass ex inhaler with or without VHC and FPM<4.7μm.
• In the first series of measurements, the primed and shaken pMDI was actuated 5 times into the lips of the OC without a VHC.
• In the second series, we repeated the measurements with the original pMDI, this time adding an antistatic AeroChamber Plus* VHC/ mouthpiece.
• 2 s delay interval between pMDI actuation and starting to sample to simulate use by a poorly coordinated patient.

Fine particle mass fraction <4.7 μm aerodynamic diameter (FPF<4.7μm) and fine particle mass/actuation (FPM<4.7μm) is illustrated Table 1 for the pMDI alone and in Table 2 for the pMDI with VHC with 2 s delay following actuation before initiating sampling.

• The findings of Xi and Yang (J Drug Delivery Sci Technol. 2019; 49: 674-682.) who found a 6%–25% reduction in medication delivery efficiency caused by the tongue are comparable with the 26% increase in FPM<4.7μm observed going from Model 1 to Model 2, in which the volume occupied by the tongue was decreased from 100% to 60% (Table 1).
• This change was also accompanied by a significant increase in FPF<4.7μm (unpaired t-test, p <0.001), indicating that the location of the tongue when fully present, could also capture some fine particles <4.7 μm aerodynamic diameter, as well as coarser particles.
• Importantly, the further reductions in tongue volume by 70% (Model 3) and 100% (model 4) are not meant to represent clinical situations, but to serve as a means of demonstrating the progressive changes in these two measures of interest, moving to an extreme situation with no tongue present.
• FPF<4.7μm for the pMDI alone increased significantly with larger OC volumes (1-way ANOVA, p <0.0001) from 16.7 ± 3.6% with the full tongue volume present (model 1) to 38.5 ± 6.5% when the tongue was completely removed (Model 4).
• This change was associated with an increase in FPM<4.7μm from 12.9 ± 2.1 μg/ actuation to 26.5 ± 3.8 μg/actuation (p <0.0001).
• In contrast, when the VHC was present, with a 2 s delay between actuation and inhalation, FPF<4.7μm remained relatively consistent across the different tongue volume conditions and FPM<4.7μm changed much less than with the MDI alone.

This study confirms the importance of the tongue in controlling the amount of medication as fine particles capable of reaching the airways of the lungs.

If a VHC is absent, it confirmed that fine particle mass will be reduced compared with the case when a VHC is interposed between inhaler and the mouth of the patient.

If a VHC is present, it showed consistent fine particle delivery, independent of tongue position, without the need to coordinate actuation with inhalation.

When assessing inhaler technique a VHC should be recommended, and if not, tongue position should be discussed with the patient.