Erratum to "Fragmentation dynamics of single agglomerate-to-wall impaction" [Powder Technology 378 (2021) 561-575, DOI: 10.1016/j.powtec.2020.10.021].

[This corrects the article PMC8724865.].

Fragmentation dynamics of single agglomerate-to-wall impaction.

The de-agglomeration characteristics of single agglomerate-wall impaction are examined using high-resolution shadowgraph imaging. Experiments are performed to investigate the effects of constituent particle size (D 50 from 3-7 µ m) and air velocity on the individual size and velocity of de-agglomerated fragments at conditions relevant to dry powder inhalation systems. De-agglomerated fragment area and trajectories were used to differentiate between pseudo-elastic and inelastic collisions during de-agglomeration. Advanced image processing techniques have enabled provision of joint population distributions of fragment area and aspect ratio, which identify a bimodal dispersion of fragments during de-agglomeration. The bimodality is destroyed with increasing air velocity and also generally diminishes with time after impact. The experiment presented forms a platform for the detailed quantitative characterisation of de-agglomeration behaviour and can be useful towards the development and validation of related computational models for pharmaceutical dry powder inhalers.

Local dynamics of pharmaceutical powder fluidization using high speed long distance microscopy and particle image velocimetry.

The local dynamics of fluidized pharmaceutical carrier powders in a turbulent channel flow was studied using particle image velocimetry (PIV) and High-speed, long-distance microscopy (HS-LDM). Four different lactose powders which have been used as a drug carrier in dry powder inhalers were used in this study. These powders have median powder particle diameters ranging between 61 and 121 µm. Air flow velocities ranging between 13.3 m/s and 66.7 m/s were examined. In addition, the effect of grid blockage ratio (ranging from ~25% to ~40% of the area of channel cross-section) was also investigated. Results show that the high-speed, long-distance microscopy (HS-LDM) technique was able to capture the mean velocity of the particles, and the results corresponded well with the PIV measurements. Results from the high-speed, long-distance microscopy (HS-LDM) method also demonstrate that the span of particle velocity closely follows that of the particle size distribution both for cohesive and non-cohesive powders. This study contributes towards an improved understanding of pharmaceutical carrier dynamics in turbulent channel flows and demonstrates how advanced image processing can be used to capture local particle dynamics.

Effect of an upstream grid on the fluidization of pharmaceutical carrier powders.

The influence of grid generated mixing on the fluidization of pharmaceutical carrier powders is studied in a channel-flow experiment using direct high-speed imaging and particle image velocimetry (PIV). Four different lactose powders with mass median diameters that range between 61 µm and 121 µm are used. The degree of powder mixing in the flow as a function of grid position relative to the powder bed and grid area blockage ratios (ranging from ~25% to ~40%) is studied for a range of flow-rates. The study presents comprehensive mappings of how pharmaceutical powders are fluidised under the influence of mixing, by examining powder bed morphology, powder emptying rate, and the local flow-field surrounding the pocket. The use of a grid results in higher evacuation percentages (void fraction) and a faster evacuation rate but is associated with randomized evacuation behaviour as observed from the powder bed morphology. Use of a grid can enable evacuation of powder at lower overall flow-rates, which may have important implications on respiratory drug delivery. PIV results show the trend of mean velocities with the mass median powder diameter and demonstrates how a grid with lower blockage ratio can increase the degree of mixing of the evacuating powder and make the evacuation process more rapid. This study contributes towards a better understanding of fluidization processes as relevant to dry powder inhaler devices and sheds light on how simple design alterations, such as adding an upstream grid, can be incorporated to optimise device effectiveness.

Airway geometry, airway flow, and particle measurement methods: implications on pulmonary drug delivery.

INTRODUCTION: The effectiveness of drug delivery to the lungs is inextricably linked to the fundamental interactions that occur between particles and flow in the extrathoracic airway. Research in this field requires time resolved in-vivo and in-vitro measurements of three separate, yet intricately linked parameters: i) airway flow, ii) airway geometry, and iii) drug particle characteristics. A number of recent significant developments have been made in the experimental diagnostic tools used to characterise these parameters. AREAS COVERED: In this review paper, we summarize the key recent findings that have resulted from the implementation of laser and optical diagnostic tools towards characterization of airway flow, extrathoracic airway geometry and drug particle characteristics. These three areas are discussed together, enabling a critical review of the implications of recent experimental findings on likely future developments in drug delivery to the lungs. EXPERT OPINION: Improvements in drug delivery systems will result through implementation of laser and optical based diagnostic methods that can spatially and temporally resolve particle and agglomerate shape, size and dynamic characteristics. Design of inhaler devices must be done in parallel to developing realistic in-vitro upper airway replicas that account for physiological differences between patient groups, as a function of respiratory disease severity.