Chapter 3 - In Vitro Testing of Pharmaceutical Aerosols
This chapter includes following sub-chapters:
Chapter 3.1 - Particle Size Measurements
Jolyon P. Mitchell PhD, FRSC (UK), CChem, CSci
Particle size measurement of aerosolized particles from orally inhaled and nasal drug products (OINDPs) can be used to assess likely deposition distribution in the human respiratory tract (HRT). Size is normally expressed in terms of aerodynamic diameter, since this scale directly relates to the mechanics of particle transport from inhaler to deposition locations. The multistage cascade impactor (CI) is the principal apparatus used to size-fractionate aerosols in terms of their aerodynamic particle size distributions (APSDs). Clinically meaningful metrics, such as fine and coarse particle mass fractions, can be determined from the cumulative mass-weighted APSD.
Chapter 3.2 - Fine Particle Fraction: The Good and the Bad
Stephen P. Newman, PhD
Fine particle fraction (FPF) is defined in general terms as the fraction or percentage of the drug mass contained in an aerosol cloud that may be small enough to enter the lungs and exert a clinical effect. An aerodynamic diameter of 5 μm represents the approximate border between “fine” and “coarse” particles, but there is no universally agreed upon definition of FPF in terms of an aerodynamic particle size range. FPF alone does not adequately describe a heterodisperse aerodynamic particle size distribution, and it needs to be combined with another measure or measures indicating the width of the distribution. When determined using techniques specified in United States and European Pharmacopeias, FPF is measured by cascade impactors that have straight-sided ninety degree inlets through which air is drawn at a constant rate.
Chapter 3.3 - Use of Airway Replicas in Lung Delivery Applications
Laleh Golshahi, PhD, Warren H. Finlay, PhD, and Herbert Wachtel, PhD
The use of extrathoracic airway replicas in optimization of drug delivery to the lungs with nebulizers, dry powder inhalers (DPIs) and pressurized metered-dose inhalers (pMDIs) is discussed. Such airway replicas have been useful in evaluating new pulmonary drug delivery platforms mainly based on the comparison of the total lung dose (TLD) and the aerodynamic particle size distribution (APSD) of the aerosol distal to the physical models. The ability of these in vitro methods to replicate in vivo results has allowed advancements in respiratory drug delivery and in the accuracy and utility of in vitro-in vivo correlations (IVIVCs).
Chapter 3.4 - Empirical Deposition Correlations
Andrew R. Martin, PhD and Warren H. Finlay, PhD
Traditionally, empirical correlations for predicting respiratory tract deposition of inhaled aerosols have been developed using limited available in vivo data. More recently, advances in medical image segmentation and additive manufacturing processes have allowed researchers to conduct extensive in vitro deposition experiments in realistic replicas of the upper and central branching airways. This work has led to a collection of empirical equations for predicting regional aerosol deposition, especially in the upper, nasal and oral airways. The present section reviews empirical correlations based on both in vivo and in vitro data, which may be used to predict total and regional deposition.
