Beyond the bench: Aerosol analysis and the physics of MDI performance

Modern drug delivery is built on an architecture of precision and predictability to ensure patient safety. Behind every successful inhalation therapy lies a methodical application of analytical science that characterizes the behavior of complex aerosol systems. In this Beyond the bench blog, we examine how this analytical backbone supports the development of pressurized metered-dose inhalers (pMDIs). 

Defining inhalation performance in pMDIs

Inhalation drug delivery performance in pMDIs depends on how consistently an aerosol plume is formed and dispersed. Small shifts in aerosolization (a mechanistic process whereby bulk liquid disintegrates into respirable droplets) can alter where drug particles deposit in the lung, directly affecting therapeutic outcomes and dose reproducibility.

Plume geometry and spray pattern define this relationship by translating formulation and device interactions into measurable performance. Regulatory agencies expect these attributes to remain consistent across development, scale-up and commercial supply, with in vitro data supporting bioequivalence and ongoing product quality.

Where does aerosol variability arise in pMDIs?

Variability in aerosol performance stems from interactions between formulation properties and device architecture. Suspension-based systems are particularly sensitive to changes in active pharmaceutical ingredient (API) particle size distribution, morphology and surface energy, which influence how particles disperse during actuation [1].

Interactions between the valve, actuator and propellant determine key plume characteristics. Even small differences in actuator orifice shape can shift spray characteristics, as irregular geometries have been shown to produce atypical spray patterns compared with well-defined circular orifices [2].

These interacting factors define plume behavior, making targeted analytical insight essential for predicting and controlling variability.

How are spray pattern and plume geometry measured?

Critical quality attributes (CQA) are quantified using advanced optical diagnostic techniques and imaging systems that capture the physical properties of the spray. Plume geometry and spray pattern analysis assess the angle, symmetry and consistency of the aerosol across multiple actuations. Systems such as SprayVIEW and Viota software allow analytical specialists to measure these attributes with high precision. 

Aerodynamic particle size distribution testing further assesses the fine particle fraction to predict deposition in the deep lung. Combined, these methods establish a clear connection between plume structure and expected in vivo performance.

How is aerosol performance controlled in development and manufacturing?

Control begins with formulation design that supports stable suspension behavior and consistent aerosolization. Managing particle interactions and minimizing agglomeration supports consistent dispersion during actuation, reducing variability in delivered dose [3].

Formulation, actuator and valve design are refined through iterative testing, with analytical data guiding adjustments to orifice geometry and spray dynamics. Spray pattern testing can also be applied as a quality control tool for incoming components, enabling early detection of manufacturing variation before it impacts finished product performance.

Integrating analytical data across development and manufacturing ensures that decisions are grounded in measurable performance. This approach supports robust validation strategies and maintains alignment with regulatory expectations as processes scale.

What is the lifecycle impact on bioequivalence, tech transfer and commercial reliability?

Consistent analytical data demonstrates equivalence in plume geometry, spray pattern and aerodynamic particle size distribution, supporting bioequivalence submissions and regulatory review.

The same data supports reliable tech transfer, consistent batch release and alignment across global supply networks, while enabling ongoing monitoring strategies that sustain product quality throughout the lifecycle.

By positioning aerosol analytics as a core development and manufacturing capability, plume geometry and spray pattern become defined performance attributes that can be actively controlled rather than retrospectively assessed.

Don’t miss the next chapter 

Analytical science continues to expand its role as inhalation technologies evolve to meet new sustainability goals. The transition to NGPs with low global warming potential (low-GWP) introduces new challenges in compatibility, stability and performance that require equally robust analytical strategies.

Our next article in the Beyond the bench series will examine how analytical approaches support propellant reformulation without compromising therapeutic performance, with a focus on maintaining consistency across development and scale.

If you are exploring how to strengthen control over pMDI performance or navigate complex reformulation challenges, contact our team to discuss how our analytical expertise can support your program. 

References

1. Berry, Julianne, Lukeysha C Kline, et al. “Influence of the size of micronized active pharmaceutical ingredient on the aerodynamic particle size and stability of a metered dose inhaler.” Drug development and industrial pharmacy. 30.7 (2004): 705-714. Print. https://pubmed.ncbi.nlm.nih.gov/15491048/ 
2. Smyth, H., A. J. Hickey, et al. “Spray pattern analysis for metered dose inhalers I: Orifice size, particle size, and droplet motion correlations.” Drug development and industrial pharmacy, 32.9 (2006): 1033–1041. Print. https://www.rti.org/publication/spray-pattern-analysis-metered-dose-inhalers-orifice-size-particle-size-droplet-motion-correlations 
3. Duke, Daniel J., Harry N. Scott, et al. “Drug distribution transients in solution and suspension-based pressurised metered dose inhaler sprays.” International journal of pharmaceutics. 566 (2019): 463-475. Print. https://www.sciencedirect.com/science/article/abs/pii/S0378517319304272