Investigation of drug aerosol size, delivery, and deposition in the mouth-throat airway using a soft mist inhaler (SMI): an experimental and numerical study

Abstract

Respiratory drug delivery has been a key area of research for several decades, driven by the high prevalence of pulmonary diseases and the superior treatment efficiency offered by this approach. However, despite its significant advantages, respiratory drug delivery faces major challenges, particularly low delivery efficiency and substantial drug deposition in undesired areas like the soft mist inhaler (SMI) mouthpiece, oral cavity, and throat wall. This study aimed to enhance the performance of inhalation therapy devices by leveraging insights and findings derived from experimental in-vitro and computational fluid dynamic (CFD) simulations. This study examines the size distribution of drug aerosols and their deposition efficiency in the mouth-throat airway using an SMI. The SMI is known for its high drug delivery rates, ranging from 40% to 60%, and employs a unique atomization process through the Uniblock system to create fine particles that are ideal for lung deposition. To facilitate the research, the geometry of the mouth-throat region was constructed using three-dimensional (3D) printing technology with Ultimaker S3 and S5 printers, utilizing tough poly lactic acid (PLA) for precise and durable models. These printed geometries were then attached to a next-generation impactor (NGI) for experimental analysis. The NGI, which evaluates particle deposition and size distribution, was used to capture aerosolized particles at various stages according to their size. To quantify the deposition of the active pharmaceutical ingredient (API), high-performance liquid chromatography (HPLC) was employed at each stage and collection cup of the NGI, providing accurate measurements of drug deposition. Additionally, CFD simulations were conducted to model aerosol transport and deposition, offering valuable insights into airflow patterns, droplet size distribution, and the effects of geometric and physiological variations within the respiratory tract. In the first part of the study, SMI performance was analyzed in two simplified mouth geometries: an idealized mouth (IM) and a standard mouth (SM). The effects of nozzle positions (along with the centerline), angles, and a fixed flow rate of 30 l/min were investigated to assess their impact on aerosol deposition and size distribution. The results indicated that SMI positioning and flow rate play a dominant role in determining deposition efficiency and size distribution, with higher flow rates reducing deposition within the mouth cavity. Recirculation regions and backward flows were identified as key contributors to increased particle residence time and deposition on mouth walls. Moving the SMI nozzle forward enhanced particle velocity at the outlet and reduced deposition, particularly in the SM geometry. These findings offer a foundation for developing innovative add-on devices, such as sensors or smart mouthpieces, to guide patients—especially children and the elderly—in optimizing inhalation techniques and improving drug delivery. [...]