<i>In Vitro</i>Assessment of Dose Delivery Performance of Dry Powders for Inhalation

Abstract

The aerosol performance of engineered porous particles (PulmoSphere™) for inhalation as a function of powder properties (particle size and density) was assessed using an idealized replica of the adult human upper respiratory tract (URT) known as the Alberta mouth-throat model. Engineered placebo powders were prepared using the PulmoSphere™ technology, which is based on spray-drying an emulsion feedstock and produces porous particles with well-controlled size and density. These placebo powders are useful surrogates for a class of potent active formulations, and covered a range of particle sizes and densities, representing a particle design space relevant to dry powder inhalers. The Alberta idealized mouth-throat model was used for in vitro measurement of oropharyngeal (mouth and throat) losses and to estimate the total lung dose for different inhalation drug products. The in vitro lung doses measured with the mouth-throat model were compared to predictions of lung dose from semi-empirical numerical models of oropharyngeal deposition. Data from the mouth-throat model and numerical models were used to rank order oropharyngeal losses and flow-rate dependence in the 1–6 kPa pressure drop range. Aerosol performance of the PulmoSphere™ powders was favored by low-particle density and large geometric size, with the oropharyngeal deposition and flow rate dependence being lower for powders with median particle diameter ≥2.5 microns. In comparison, data from lactose-blend formulations showed significantly higher oropharyngeal deposition and flow rate dependence. The idealized mouth-throat model provides a reasonable in vitro estimate of dose delivered to the lungs, and is a useful tool for studying the effect of factors such as drug/device and inhalation airflow.Copyright 2014 American Association for Aerosol Research