Aerosol Synthesis of Inhalation Particles via a Droplet-to-Particle Method

ABSTRACT

Inhalation powders with consistent particle properties, including particle size, size distribution, and shape were produced with an aerosol synthesis method. Compared to conventional spray drying, the aerosol method provides better control of the thermal history and residence time of each droplet and product particle due to the laminar flow in the heated zone of the reactor where the droplet drying and particle formation take place. A corticosteroid, beclomethasone dipropionate, generally used for asthma treatment was chosen as a representative material to demonstrate the process. Spherical particles were produced with a droplet-to-particle method from an ethanolic precursor solution. The droplets produced with an ultrasonic nebulizer were carried to a heated zone of the reactor at 50–150°C where the solvent was evaporated and dry particles formed. The mass mean diameter of the particles were well within the respirable size range (approximately 2 μm). The geometric standard deviation (GSD) of produced particles was approximately 2. The particle surface structure varied from smooth to rough depending on the degree of particle crystallinity and was affected by the thermal history of the particle. Amorphous particles with smooth surface were most likely obtained due to the rapid evaporation of the solvent from the droplet combined with the slow diffusion of the beclomethasone dipropionate molecule. The amorphous particles were transformed slowly to crystalline particles in the open atmosphere. In addition, the particle surface structure changed from smooth to rough during storage. The process was accelerated by thermal post-annealing. However, additional heating also increased particle sintering. By optimizing the reactor parameters, and thus increasing the molecular diffusion, stable, crystalline particles were produced at 150°C.     

Particle Size of Inhalation Aerosol Systems I: Production of Homogenous Dispersions

Abstract

The methods used to size inhalation aerosol a and the problems involved in producing an homogenous cloud of aerosol particlea are reviewed. Particle size analyses were carried out using a Royco 225/508 particle size analyser. A number of variables such as sensor head position have been examined under conditions of constant temperature and humidity. It is shows that a dilution of the aerosol cloud into a large volume (360 1) gives a satisfactory number of particles in the sample volume. The positioning of the sensor head is not critical provided that adequate air turbulence can be generated using sleeved sintered-bearing fans. The air flow rate sust be controlled so that air passes over the sensor at not anre than 0.58 m.s^?1. The length of time required to produce a uniform diatribution is shown to be about 10 secs.     

The effectiveness of an air cleaner in controlling droplet/aerosol particle dispersion emitted from a patient's mouth in the indoor environment of dental clinics

Dental healthcare workers (DHCWs) are at high risk of occupational exposure to droplets and aerosol particles emitted from patients'' mouths during treatment. We evaluated the effectiveness of an air cleaner in reducing droplet and aerosol contamination by positioning the device in four different locations in an actual dental clinic. We applied computational fluid dynamics (CFD) methods to solve the governing equations of airflow, energy and dispersion of different-sized airborne droplets/aerosol particles. In a dental clinic, we measured the supply air velocity and temperature of the ventilation system, the airflow rate and the particle removal efficiency of the air cleaner to determine the boundary conditions for the CFD simulations. Our results indicate that use of an air cleaner in a dental clinic may be an effective method for reducing DHCWs'' exposure to airborne droplets and aerosol particles. Further, we found that the probability of droplet/aerosol particle removal and the direction of airflow from the cleaner are both important control measures for droplet and aerosol contamination in a dental clinic. Thus, the distance between the air cleaner and droplet/aerosol particle source as well as the relative location of the air cleaner to both the source and the DHCW are important considerations for reducing DHCWs'' exposure to droplets/aerosol particles emitted from the patient''s mouth during treatments.     

PARTICULATE CONCENTRATION IN AUTOMOBILE PASSENGER COMPARTMENTS

An experimental study of the dust concentration in automobile passenger compartments was conducted to understand how driving conditions and a vehicle's ventilation system can affect cabin air quality. The results of this study are essential for designing appropriate cabin air filters and developing proper test procedures.

The particle size distribution of atmospheric contaminants entering the vehicle's passenger compartment through air registers and in the occupants' breathing zone was measured using an optical particle counter. The concentration and size distribution of aerosol in the cabin was found to be dependent on traffic conditions, road surface, environmental conditions (e.g., weather) and ventilation mode. In all cases over 90% of the particles were smaller than 1 µm. The vehicle's HVAC system (evaporator core) reduces the concentration of aerosol entering the car interior, especially larger particles. Commercial vehicle ventilation filters decrease particle concentrations in a driver's breathing zone for all particle sizes. However, the reduction in the submicron particle range is not sufficient to substantially improve air quality in the passenger cabin.     

Generation of aerosol nanoparticles by the multi-spark discharge generator

We have experimentally studied the formation of aerosol nanoparticles synthesized by the processes of electro-erosive wear of three pairs of electrodes upon a series connection on the discharge circuit that is controlled by a frequency generator of pulsed currents. Using a diffusion aerosol spectrometer, we have measured the particle-size distribution in the flows of aerosols upon varying velocity V of air flow, repetition frequency of discharge f, and single discharge energy W. It has been established that when controlling parameters of generator one can obtain nanoparticles (agglomerates of nanoparticles) in a wide range of mean size values d _mean from 8 to 75 nm with a geometric standard deviation (GSD) of 1.3–2.0. The growth of agglomerates of nanoparticles monotonously depends on the residence time of particles in the gas and the particle concentration.     

Evolution of nonequilibrium aerosol parameters in crown-streamer discharge plasma

Nonstationary parameters of an aerosol formed from unsaturated vapors of styrene and n-hexane in a pulsed crown-streamer discharge in air or argon at atmospheric pressure have been studied. In the initial stage of aerosol formation, the concentration of aerosol particles was on the order of 10⁷ cm⁻³. The characteristic time of nonequilibrium hexane aerosol degradation in the experimental chamber amounted to several hours. The aerosol particle size distribution function has a bimodal shape. Within the first seconds upon aerosol formation, the maximum particle size does not exceed 0.6 μm, whereas in several hours, the boundary of the particle size spectrum reaches the micron range.     

Characterization of a Nose-Only Inhalation Exposure System for Ectromelia Virus Infection of Mice

A nose-only inhalation exposure system (NOIES) was evaluated for its performance in this study using test polystyrene latex spheres (PLS) and ectromelia virus (ECTV), which is a surrogate for variola virus, the causative agent of smallpox. The test aerosol sampled at the various ports of the NOIES was found to be consistent in particle size and number concentration. ECTV bio-aerosol was delivered to A/J mice strain and the lethal dose (LD₅₀) value at which mortality was 50% was found to be 41 PFU/mL. The airborne ECTV particles were sampled and collected on TEM grids for particle size imaging using a scanning electron microscope (SEM) and structural integrity imaging using a transmission electron microscope (TEM). SEM images of ECTV after aerosolization showed the virions to be coated with the smaller size solute particles generated from the buffer solution during the aerosolization process. TEM images showed the ECTV to be structurally intact after undergoing the process of aerosolization. From the viable ECTV particle size distribution, the geometric mean diameter (GMD) of the airborne ECTV particles was calculated to be 278 nm with a geometric standard deviation (GSD) of 1.73.     

气溶胶粒子在裂隙中穿透特性实验研究

为研究气溶胶颗粒通过房屋裂隙进入室内的穿透特性,用铁质矩形裂隙在实验室进行模拟实验研究。结果表明:气溶胶粒径、气体流速和裂隙高度对气溶胶的穿透率影响比较显著;流速和裂隙高度增加会增大气溶胶的穿透率;不同粒径的气溶胶在相同实验条件下穿透率存在明显差异,最易穿透的是粒径在0.5μm左右的粒子,小粒子和大粒子分别在Brownian扩散作用和重力沉降作用下穿透率低。     

Aerosol Synthesis of Inhalation Particles via a Droplet-to-Particle Method

Inhalation powders with consistent particle properties, including particle size, size distribution, and shape were produced with an aerosol synthesis method. Compared to conventional spray drying, the aerosol method provides better control of the thermal history and residence time of each droplet and product particle due to the laminar flow in the heated zone of the reactor where the droplet drying and particle formation take place. A corticosteroid, beclomethasone dipropionate, generally used for asthma treatment was chosen as a representative material to demonstrate the process. Spherical particles were produced with a droplet-to-particle method from an ethanolic precursor solution. The droplets produced with an ultrasonic nebulizer were carried to a heated zone of the reactor at 50-150°C where the solvent was evaporated and dry particles formed. The mass mean diameter of the particles were well within the respirable size range (approximately 2 μm). The geometric standard deviation (GSD) of produced particles was approximately 2. The particle surface structure varied from smooth to rough depending on the degree of particle crystallinity and was affected by the thermal history of the particle. Amorphous particles with smooth surface were most likely obtained due to the rapid evaporation of the solvent from the droplet combined with the slow diffusion of the beclomethasone dipropionate molecule. The amorphous particles were transformed slowly to crystalline particles in the open atmosphere. In addition, the particle surface structure changed from smooth to rough during storage. The process was accelerated by thermal post-annealing. However, additional heating also increased particle sintering. By optimizing the reactor parameters, and thus increasing the molecular diffusion, stable, crystalline particles were produced at 150°C.     

The control of particle size distribution for fabricated alumina nanoparticles using a thermophoretic separator

Control of the particle size distribution of fabricated alumina nanoparticles from general alumina powder with a large geometric standard deviation (GSD) was studied. A thermophoretic separator was used to control the GSD of the nanoparticles, and unevaporated and primary particles were separated to yield a small GSD. The fabricated nanoparticles were characterized by field emission scanning electron microscopy (FESEM) and a scanning mobility particle sizer (SMPS). We confirmed that the GSD of the nanoparticles was controlled by the thermophoretic separator. A temperature difference between 79 K and 151 K was applied to the thermophoretic separator for control of the nanoparticle GSD. The GSD of the fabricated alumina nanoparticles was improved from 1.74 to 1.44.     

EULERIAN AND LAGRANGIAN SIMULATIONS OF PARTICLE DEPOSITION FROM A POINT SOURCE IN A TURBULENT CHANNEL FLOW

ABSTRACT

Results comparing Eulerian and Lagrangian simulations of particle deposition from a point source in a channel are presented. The mean turbulent flow field is simulated using a two-equation k-? turbulence model. In the first, approach, diffusion of aerosol particles is studied by solving the corresponding advection-diffusion equation. Deposition of particles in the intermediate size range are analyzed by considering both the turbulent eddy diffusion and the eddy impaction processes, as well as the Brownian diffusion effects. In the second approach, the turbulence fluctuating velocity field are numerically simulated as a Gaussian random process. The Lagrangian trajectories of aerosol particles in the channel are then evaluated by solving the corresponding particle equation of motion. Effects of Brownian diffusion on particle motions are also included. A series of digital simulations for particles of various sizes which are released at different locations across the channel are carried out. Depositions of different size particles on the wall under a variety of conditions are analyzed. The relative significance of turbulence and Brownian effects are also discussed.     

TiCI4高温气相氧化合成纳米二氧化钛颗粒的研究Ⅰ.颗粒粒度控制

在高温气相反应器中,利用ＴｉＣＩ４氧化反应制备纳米ＴｉＯ２颗粒,研究了操作参数对颗粒粒度的影响。结果表明提高氧气预热温度,有利于促进成核,制备的ＴｉＯ２粒径小、分布窄;ＴｉＯ２粒度随着反应温度提高、停留时间延长或ＴｉＣＩ４起始浓度增加而增大;加入ＡＩＣＩ３对ＴｉＯ２颗粒形态有较大影响,ＴｉＯ２平均晶粒尺寸随着掺铝量增加而减小。     

Deposition of aerosol particles in a model vitreous chamber

The purpose of this study was to assess quantitatively the aerosol deposition in a model eye chamber to identify the mechanism(s) of deposition and delivery efficiency for application in retinal disease treated with vitrectomy. Dry aerosol particles were produced with mixtures of fluorescein and a variable concentration of cesium chloride, which ranged in aerodynamic size from 0.6 to 1.3 μm. The aerosol was injected through a small inlet tube into Teflon chambers that had a vented, spherical cavity (diameter ?"). Two filling times of 60 s and 90 s were used. Although significant loss occurred in the syringe, the mass deposited within the chambers increased with aerosol concentration and ranged from 0.5 to nearly 15 μg. Between 60 and 90% of the mass was deposited on the lower surface of the chamber. The mechanism of deposition was consistent with diffusion through a boundary layer during filling followed by sedimentation of the remaining suspended aerosol particles. Based on these results, an aerosol with a median particle size of 1.3 μm was shown to provide a therapeutically effective dose of 5-fluorouracil. The approach is general and can be applied to the aerosol delivery of other drugs to the vitreous chamber.     

Particle Size of Inhalation Aerosol Systems I: Production of Homogenous Dispersions

The methods used to size inhalation aerosol a and the problems involved in producing an homogenous cloud of aerosol particlea are reviewed. Particle size analyses were carried out using a Royco 225/508 particle size analyser. A number of variables such as sensor head position have been examined under conditions of constant temperature and humidity. It is shows that a dilution of the aerosol cloud into a large volume (360 1) gives a satisfactory number of particles in the sample volume. The positioning of the sensor head is not critical provided that adequate air turbulence can be generated using sleeved sintered-bearing fans. The air flow rate sust be controlled so that air passes over the sensor at not anre than 0.58 m.s^-1. The length of time required to produce a uniform diatribution is shown to be about 10 secs.     

凝聚式单分散气溶胶发生技术的探讨

实现高效空气过滤器计数法的首要任务就是选择合适的气溶胶发生器。本文中首先介绍了凝聚式单分散气溶胶发生器的工作原理、构造形式、发生流程以及国内外研究进展,然后详细分析了其发生气溶胶粒子粒径和浓度的影响参数;作者认为凝聚式单分散气溶胶发生器能够快速地发生浓度可调的、适用于高效空气过滤器效率测试的单分散亚微米气溶胶粒子,可以满足国家标准《高效空气过滤器性能试验方法》的修订对气溶胶发生装置的要求。     

Effect of Air Flow and Acceleration on Particle Size of Dry Powder Aerosols determined by Time-of-Flight Aerosol Beam Spectrometry

ABSTRACT

The effect of air flow and acceleration on the particle size distributions of two Turbuhalers containing drug loads of 0.5 and 1.3 mg per dose was determined with a time-of-flight aerosol beam spectrometer (Aerosizer®). While the particle size of both inhalers decreased with increasing flow and acceleration, the distributions became narrower and variability was reduced. Simultaneously, a decrease in the number and mass of particles measured was observed which was more pronounced for the 1.3 mg dose. Additionally the count rate for the 1.3 mg dose was lower than for 0.5 mg. These observations were accompanied by a remarkably fine particle size distribution for the high dose Turbuhaler®. It was concluded that the quantity of particles in the DPI aerosols exceeded the resolution of the Aerosizer, erroneously shifting the size distributions towards smaller diameters.

In addition, the DPI aerosols were analyzed with a Four Stage Impinger to evaluate the results. The particle size estimates obtained using the impinger were in the same range as those obtained at an acceleration of 5 L/s2 using the Aerosizer to study the 0.5 mg Turbuhaler. The Aerosizer produced significantly smaller particle sizes than the impinger in all cases evaluating the 1.3 mg Turbuhaler, supporting the theory of distorted particle size distributions due to particle overload.     

EARLY-STAGE EVOLUTION OF PARTICLE SIZE DISTRIBUTION DUE TO GRAVITATIONAL COAGULATION

ABSTRACT

Evolution of the particle size distribution of an aerosol undergoing gravitational coagulation in early time stages was numerically investigated. The moment method was also applied in initiating a simple approach to the changes of particle size distribution parameters. Finally, an analytical solution was developed approximating the collision kernel into a form suitable for the analysis. The results underwent analysis by comparison. The derived analytical solution was found to be in good agreement with the numerical moment method. However, the results of the moment method do not exactly coincide with the results of the direct numerical integration because the particle size distribution does not attain the log-normal size distribution form.     

Development and testing of a detection method for liquid chromatography based on aerosol charging

Aerosol-based detection methods for HPLC in which HPLC effluent is converted to an aerosol and detected optically have been employed in the past. This paper describes a new aerosol-based detection method for HPLC, which we name aerosol charge detection. This detection method also involves generation of an aerosol but with aerosol detection by charging aerosol particles and measuring the current from the charged particle flux. A commercial electrical aerosol size analyzer was used for the aerosol detection. The constructed detector was tested using flow injection analysis with water as the mobile phase, and the signal response was found to be linear for sodium sulfate over the concentration ranges of 0.2-100 microg mL(-1) using one of the nebulizers. Minimum mass and concentration detection limits using the more efficient nebulizer were estimated to be 0.2 ng and 10 ng mL(-1), respectively. Behavior for most of the other compounds tested was similar with some differences in sensitivity. Testing the detector using reversed phase HPLC for glucose gave a range of linear response and detection limits that were similar to the flow injection analysis studies. Under most HPLC conditions, the noise will primarily be a function of solvent impurities; however, the electrical aerosol size analyzer allows the removal of small charged particles to improve the signal-to-noise ratio.     

Computational Fluid Dynamics Study of Flow and Aerosol Concentration Patterns in a Ribbed Smoked Sheet Rubber Factory

A computational fluid dynamics (CFD) method was used to investigate velocity, temperature, particles trajectories, and aerosol concentration in a natural ribbed smoked sheet rubber factory. A model to improve the smoke aerosol particle ventilation was proposed. The simulation was performed using turbulent free convection flows where the Rayleigh number was between 5.3838 × 10¹⁰ and 33.2003 × 10¹⁰. A total of 2,159,347 mesh volumes were applied to the entire ribbed smoked sheet rubber cooperative. Results from the CFD simulation and experiment showed positive results. The air containing smoke particles moved naturally from ventilating lids of the smoke room to the roof. The smoke particles followed the airflow fields at the junction of the roof and traveled to workplace areas. Results show that the thick cloud of smoke particles remained in the workplace after traveling for more than 200 m. Particle concentration was high in the area above the ceiling and lower along the elevation in a downward direction. This is potentially harmful to the employees who work in the factory for long periods of time. Modification of the roof to include a ridge vent showed considerable improvement in ventilation, which largely decreased the aerosol particle concentration inside the factory.     

CARBONACEOUS AEROSOLS-SINGLE SCATTERING ALBEDO AND EFFECT ON WEATHER HEATING

An experimental setup for the measurement of single scattering albedo of aerosol particles was described. The setup consisted of a nephelometer to measure aerosol light scattering coefficient, a photoacoustic spectrometer to measure aerosol light absorption coefficient, a Single Particle Aerodynamic Relaxation Time (SPART) Analyzer to measure aerosol aerodynamic size distribution, and an aethalometer to measure aerosol mass concentration. Simultaneous measurements of these parameters of a test carbonaceous aerosol were used to determine its single scattering albedo.

At the other hand, a theoretical model based on a “two-stream approximation” was developed and used to calculate the effect of an atmospheric aerosol layer on either global or regional weather heating. It appears that carbonaceous particles in atmosphere may contribute to global temperature rise.

Finally a method of measuring single scattering albedo of single particle by the use of an electrodynamic trap was suggested for studying the effect of different physical states and shapes of particles.