How Particle Size Changes Lung Deposition: A Physical Modeller’s Perspective

N Stevens, D Prime

The aerodynamic particle size of an inhaled medicine plays a very important role in determining the drug dose delivered to the lung and also how that dose is partitioned between the different types of lung airways. Dose delivered to bronchi, bronchioles and alveolated airways may be expected to result in different pharmacological and clinical outcomes as a result of the differing physiologies of these airway regions[1]. Unfortunately it is not yet possible to directly measure the exact drug dose delivered to each region so inferences are made by comparing pharmacokinetic and pharmacodynamic outcomes with other surrogate measurements of the regional lung dose[2]. Here it is demonstrated using illustrative examples from the literature how use of a simple mathematical model can help ensure that interpretations of experimental data are consistent with lung deposition physics. These include two validation datasets and one example of a combination Dry Powder Inhaler (DPI) product. Both the math model and the reference experimental literature (Stahlhofen et al[3]) indicate that particles of all sizes in the range 6-0.5μm deposit in all airway regions to some degree. Changes in particle size within this range cause a quantitative shift in the dose delivered to the larger and smaller airways but there is no qualitative change in the location of deposition. This is at variance with some interpretations of experimental data in the literature, thus the value of referring to a simple math model to obtain a physics-driven analysis is demonstrated.

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