Effect of patient inhalation profile and airway structure on drug deposition in image-based models with particle-particle interactions

Int J Pharm. 2022 Jan 25:612:121321. doi: 10.1016/j.ijpharm.2021.121321. Epub 2021 Dec 4.

Abstract

For many of the one billion sufferers of respiratory diseases worldwide, managing their disease with inhalers improves their ability to breathe. Poor disease management and rising pollution can trigger exacerbations that require urgent relief. Higher drug deposition in the throat instead of the lungs limits the impact on patient symptoms. To optimise delivery to the lung, patient-specific computational studies of aerosol inhalation can be used. However in many studies, inhalation modelling does not represent situations when the breathing is impaired, such as in recovery from an exacerbation, where the patient's inhalation is much faster and shorter. Here we compare differences in deposition of inhaler particles (10, 4 μm) in the airways of three patients. We aimed to evaluate deposition differences between healthy and impaired breathing with image-based healthy and diseased patient models. We found that the ratio of drug in the lower to upper lobes was 35% larger with a healthy inhalation. For smaller particles the upper airway deposition was similar in all patients, but local deposition hotspots differed in size, location and intensity. Our results identify that image-based airways must be used in respiratory modelling. Various inhalation profiles should be tested for optimal prediction of inhaler deposition.

Keywords: Aerosol deposition; Computational fluid dynamics; Drug dosimetry; Metered-dose inhaler; Patient-specific modelling.

MeSH terms

  • Administration, Inhalation
  • Aerosols
  • Humans
  • Lung*
  • Nebulizers and Vaporizers*
  • Particle Size

Substances

  • Aerosols