High time resolution measurements of droplet evaporation kinetics and particle crystallisation.

A refined technique for observing the complete evaporation behaviour of free-falling droplets, from droplet generation to complete solvent evaporation, with ultra-high time resolution is introduced and benchmarked. High-resolution phase-delay stroboscopic imaging is employed to simultaneously resolve the evolving droplet morphology, geometric and aerodynamic diameters, throughout the evaporative lifetime with a user-controlled < µs timescale. This allows rapid, complex morphological changes, such as crystallisation events, to be clearly observed and the corresponding mechanisms to be inferred. The dried particles are sampled for offline SEM analysis and the observed morphologies compared to the inflight imaging. Density changes can be calculated directly from the deviation between the geometric and aerodynamic diameters. The full capabilities of the new technique are demonstrated by examination of the different evaporation behaviours and crystallisation mechanisms for aqueous sodium chloride droplets evaporating under different ambient relative humidity (RH) conditions. The crystallisation window, defined as the time taken from initial to complete crystallisation, is shown to be RH dependent, extending from 0.03 s at 20% RH and 0.13 s at 40% RH. The different crystallisation mechanisms observed during the experiments are also clearly reflected in the final structure of the dry particles, with multi-crystal structures produced at low RH compared to single-crystal structures at higher RH. It is anticipated that this technique will unlock measurements which explore the evaporation behaviour and crystallisation mechanisms for rapid, complex droplet drying events, and with increasingly non-ideal solutions, relevant to industrial applications.

Studies of competing evaporation rates of multiple volatile components from a single binary-component aerosol droplet.

The simultaneous evaporation and condensation of multiple volatile components from multicomponent aerosol droplets leads to changes in droplet size, composition and temperature. Measurements and models that capture and predict these dynamic aerosol processes are key to understanding aerosol microphysics in a broad range of contexts. We report measurements of the evaporation kinetics of droplets (initially ∼25 µm radius) formed from mixtures of ethanol and water levitated within a electrodynamic balance over timescales spanning 500 ms to 6 s. Measurements of evaporation into a gas phase of varied relative humidity and temperature are shown to compare well with predictions from a numerical model. We show that water condensation from the gas phase can occur concurrently with ethanol evaporation from aqueous-ethanol droplets. Indeed, water can condense so rapidly during the evaporation of a pure ethanol droplet in a humid environment, driven by the evaporative cooling the droplet experiences, that the droplet becomes pure water within 0.4 s.

An in vitro study on the deposition of micrometer-sized particles in the extrathoracic airways of adults during tidal oral breathing.

Deposition of particles in the aerodynamic diameter range of 0.5-6.7 µm was measured in nine replicas of the extrathoracic airways of adults with four sinusoidal patterns and oral breathing. The four chosen breathing patterns are typical of those occurring during natural resting breathing and during nebulization therapy. Additionally, deposition of micrometer-sized particles in the "Alberta Idealized Adult Throat," which was previously found useful in simulating the average deposition of particles during inhalation of constant flow rates, was measured during inhalation of the four sinusoidal patterns in this study. To reduce intersubject scatter in developing predictive correlations, the non-dimensional Reynolds (Re) and Stokes (Stk) numbers are used with the square root of the average cross sectional area of the oral airways as the characteristic diameter being found to reduce intersubject variability to the highest extent. Our best fit to the deposition data is given by η = [1 - 1/(1.51 x 10(5)(Stk(3.03)Re(0.25)) + 1)] x 100. Moreover, the "Alberta Idealized Adult Throat" is found to mimic average deposition, given in past in vivo studies, in the upper airways of adults during natural tidal breathing.

Mechanistic models facilitate efficient development of leucine containing microparticles for pulmonary drug delivery.

Mechanistic models of the spray drying and particle formation processes were used to conduct a formulation study with minimal use of material and time. A model microparticle vehicle suitable for respiratory delivery of biological pharmaceutical actives was designed. L-leucine was chosen as one of the excipients, because of its ability to enhance aerosol dispersibility. Trehalose was the second excipient. The spray drying process parameters used to manufacture the particles were calculated a priori. The kinetics of the particle formation process were assessed using a constant evaporation rate model. The experimental work was focused on the effect of increasing L-leucine mass fraction in the formulation, specifically its effect on leucine crystallinity in the microparticles, on powder density, and on powder dispersibility. Particle, powder and aerosol properties were assessed using analytical methods with minimal sample requirement, namely linear Raman spectroscopy, scanning electron microscopy, time-of-flight aerodynamic diameter measurements, and a new technique to determine compressed bulk density of the powder. The crystallinity of leucine in the microparticles was found to be correlated with a change in particle morphology, reduction in powder density, and improvement in dispersibility. It was demonstrated that the use of mechanistic models in combination with selected analytical techniques allows rapid formulation of microparticles for respiratory drug delivery using batch sizes of less than 80 mg.

Electrodynamic Trapping of Aerocolloidal Particles: Experimental and Theoretical Trapping Limits

Aerocolloidal particles have been trapped from an uncharged source aerosol using an electrodynamic balance. Graphite and soot particles were charged photoelectrically using a Xe2 (172 nm) excimer lamp, while particles of titanium dioxide, sodium nitrate, and diethylhexyl sebacate (DEHS) were charged using a unipolar corona charger prior to injection into the chamber. It was found that the Stokesian drag force produced by convection in the balance chamber can destabilize the levitated microparticle when it exceeds the electrostatic force required to center the particle. Although the electrostatic restoring force can be increased by increasing either the particle charge or the ac field strength, charging of the particles is more difficult as the particle diameter is decreased, which gives rise to a trapping limit. Monodisperse DEHS particles were used to determine the experimental trapping limit for unipolar charging. For the experimental apparatus used in this study, a diameter of about 1 µm was found to be the trapping limit for DEHS. Results are compared to the theoretical trapping limit calculated by a force balance on a particle exposed to motion of the surrounding gas.