In Vitro Estimation of Tracheobronchial and Alveolar Doses Using Filters

Abstract

To date, in vitro estimation of doses delivered by an inhaler to the different major regions of the lung has required combining particle size measurements of the inhaled aerosol with in silico deposition models. Such a two step process is labor and time intensive. Here, we describe instead the development of an apparatus that allows direct estimation of regional lung deposition by measurement of doses collected on purpose-built metal grid filters that mimic tracheobronchial deposition efficiency. Placing these filters downstream of the Alberta Idealized Throat and upstream of a final filter allows collection of doses depositing in the extrathoracic, tracheobronchial and alveolar regions. Artificial electrostatic deposition on the metal tracheobronchial filters is prevented by a custom inline electrostatic neutralizer. We use the resulting apparatus to estimate regional deposition with a variety of dry powder inhalers during realistic, time-varying inhalation maneuvers and three pMDIs with a constant flow rate of 30 l/min. These results are compared to those obtained with the traditional two step approach that combines cascade impaction with a regional deposition model. Good agreement is found between the two approaches, indicating that the present direct method may be an efficient, time-saving alternative method for in vitro estimation of regional lung doses.

Bioequivalence study of ipratropium bromide inhalation aerosol using PBPK modelling

“…According to this division, the respiratory tract in this PBPK model was divided into the oropharyngeal-gastrointestinal tract, bronchi, bronchioles, and alveolar regions. In vitro techniques such as cascade impactors can be used to measure the particle size distribution of an inhaled medication, and this information can be combined with inhalation profiles such as flow rate and breath hold to predict the regional lung deposition of the drug (20)(21)(22). Flow rate and breath hold were not considered to simplify the model.…”

“…Drug lung and plasma exposure following inhalation is influenced by particle deposition, drug dissolution and drug absorption. Particle deposition largely depends on aerodynamic particle size and inhalation profiles such as flow rate and breath hold (20)(21)(22). Particles with size <=5 μm had a higher probability of bronchioles deposition, and particles <=2 μm more likely to deposit in alveolar lung regions.…”