Process Analytical Technology: Application to Particle Sizing in Spray Drying

The purpose of this research was to explore the possibility of employing PAT for particle sizing during spray drying with the use of an in-line and at-line laser diffraction system. Microspheres were made using maltodextrin and modified starch as wall material and size results obtained using PAT compared with those determined with off-line laser diffraction and light microscopy. Median particle size results were highest for in-line laser diffraction, followed by at-line and off-line laser diffraction and finally light microscopy. This was due to the presence of agglomerates which were measured as discrete microspheres in the in-line set-up. At-line and off-line laser diffraction gave results more closely correlated with individual microsphere sizes due to agglomerate breakdown during the measurement process. Light microscopy allowed direct observation of the particle morphology, however, its use for particle sizing was tedious and sample size was much smaller compared to laser diffraction. Although PAT was found to be an efficient and convenient tool, careful data interpretation was needed taking into account the cohesiveness of the material measured. The at-line set-up appeared to be more suitable in this particular application.     

Comparison of a laboratory and a production coating spray gun with respect to scale-up

A laboratory spray gun and a production spray gun were investigated in a scale-up study. Two Schlick spray guns, which are equipped with a new antibearding cap, were used in this study. The influence of the atomization air pressure, spray gun-to tablet bed distance, polymer solution viscosity, and spray rate were analyzed in a statistical design of experiments. The 2 spray guns were compared with respect to the spray width and height, droplet size, droplet velocity, and spray density. The droplet size, velocity, and spray density were measured with a Phase Doppler Particle Analyzer. A successful scale-up of the atomization is accomplished if similar droplet sizes, droplet velocities, and spray densities are achieved in the production scale as in the laboratory scale. This study gives basic information for the scale-up of the settings from the laboratory spray gun to the production spray gun. Both spray guns are highly comparable with respect to the droplet size and velocity. The scale-up of the droplet size should be performed by an adjustment of the atomization air pressure. The scale-up of the droplet velocity should be performed by an adjustment of the spray gun to tablet bed distance. The presented statistical model and surface plots are convenient and powerful tools for scaling up the spray settings if the spray gun is changed from laboratory spray gun to the production spray gun. Published: January 19, 2007     

Bee foraging ranges and their relationship to body size

Bees are the most important pollinator taxon; therefore, understanding the scale at which they forage has important ecological implications and conservation applications. The foraging ranges for most bee species are unknown. Foraging distance information is critical for understanding the scale at which bee populations respond to the landscape, assessing the role of bee pollinators in affecting plant population structure, planning conservation strategies for plants, and designing bee habitat refugia that maintain pollination function for wild and crop plants. We used data from 96 records of 62 bee species to determine whether body size predicts foraging distance. We regressed maximum and typical foraging distances on body size and found highly significant and explanatory nonlinear relationships. We used a second data set to: (1) compare observed reports of foraging distance to the distances predicted by our regression equations and (2) assess the biases inherent to the different techniques that have been used to assess foraging distance. The equations we present can be used to predict foraging distances for many bee species, based on a simple measurement of body size. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Assessment of the Influence Factors on Nasal Spray Droplet Velocity Using Phase-Doppler Anemometry (PDA)

Droplet velocity is an important parameter that can be used to characterize nasal spray products. In this study, a phase-Doppler anemometry (PDA) system was used to measure the droplet velocities of nasal sprays. A survey of seven commercial nasal spray products showed a range of droplet velocities from 6.7 to 19.2 m/s, all significantly different from each other. A three-level, four-factor Box–Behnken design of experiments (DOE) methodology were applied to investigate the influences of actuation parameters and formulation properties on nasal spray droplet velocity using a set of placebo formulations. The DOE study shows that all four input factors (stroke length, actuation velocity, concentration of the gelling agent, and concentration of the surfactant) have significant influence on droplet velocity. An optimized quadratic model generated from the DOE results describes the inherent relationships between the input factors and droplet velocity thus providing a better understanding of the input factor influences. Overall, PDA provides a new in vitro characterization method for the evaluation of inhalation drugs through assessment of spray velocity and may assist in product development to meet drug delivery equivalency requirements.     

高通量自动化微生物微液滴进化培养与筛选技术及其装备化

液滴微流控由于可以快速生成大量微液滴,并实现单个液滴独立的控制,每个液滴都可以作为独立的单元进行微生物培养,因此在微生物的高通量培养方面具有独特的应用优势.然而现有研究多停留在实验室搭建和使用阶段,存在操作要求高、影响因素多、缺乏自动化集成技术等关键问题,制约了液滴微流控技术在微生物研究中的应用.文中以解决液滴微流控技...     

Droplet Characterization and Penetration of an Ultra-Low Volume Mosquito Adulticide Spray Targeting the Asian Tiger Mosquito,Aedes albopictus,within Urban and Suburban Environments of Northeastern USA

Adult control of Aedes albopictus via ultra-low volume is difficult because this species occurs primarily in peridomestic habitats where obstacles such as buildings and vegetation can disrupt spray plumes and droplet dispersion. We determined droplet penetration and characterization of a pyrethroid adulticide applied from the ground at mid (46.77 ml/ha) and maximum (93.53 ml/ha) label rates within cryptic habitats of urban and suburban environments. Droplets were collected from all habitats, with no significant differences detected between locations within the same application rate or collection method. No differences were detected in droplet densities (drops per mm²) between rates within urban environments, but more droplets were collected in urban (149.93 ± 11.07 SE) than suburban sites (114.37 ± 11.32) at the maximum label rate (P = 0.003). The excellent penetration of aerosols into cryptic habitats of an urban site was likely due to the shorter spray paths afforded by our network of roads and alleys. Mid label rates displayed similar droplet density values as maximum label rates in urban areas, indicating that lower rates may be used effectively to reduce costs, lessen non-target effects, and increase environmental stewardship. Advances in formulations and technology are driving changes in adulticide applications, leading to use of the minimum effective dose for maximum efficacy, precision, and accountability.     

Fundamental study on a gene transfection methodology for mammalian cells using water-in-oil droplet deformation in a DC electric field

We have developed a gene transfection method called water-in-oil droplet electroporation (EP) that uses a dielectric oil and a liquid droplet containing live cells and exogenous DNA. When a cell suspension droplet is placed between a pair of electrodes, an intense DC electric field can induce droplet deformation, resulting in an instantaneous short circuit caused by the droplet elongating and contacting the two electrodes simultaneously. Small transient pores are generated in the cell membrane during the short, allowing the introduction of exogenous DNA into the cells. The droplet EP was characterized by varying the following experimental parameters: applied voltage, number of short circuits, type of medium (electric conductivity), concentration of exogenous DNA, and size of the droplet. In addition, the formation of transient pores in the cell membrane during droplet EP and the transfection efficiency were evaluated.     

利用飞秒激光研究微液滴的冻结相变特性

对微液滴冻结行为的认识在低温生物学、分析化学等方面具有重要意义.引入飞秒激光实验手段研究液滴及微量生物材料(蛋白)的冻结相变特性.实验考察了样品在多次冻结过程中荧光光谱的变化规律,结果表明:生物材料与非生物材料在冻结及复温过程中的荧光光谱变化趋势存在差异,非生物试剂在冻结过程中光谱下降,经历复温后,其光谱可回复到初始状态;而蛋白在冻结过程中光谱上升,经历复温后,由于降温/升温过程对其造成的不可逆损伤,光谱无法回复到初始状态.基于此提出了用以评估生物样品活性的非接触式飞秒激光测量方法.     

Multimodal particle size distributions emitted from HFA-134a solution pressurized metered-dose inhalers

The purpose of this research was to investigate the measurement and in vitro delivery implications of multimodal distributions, occurring near or in the respirable range, emitted from pressurized metered-dose inhalers (pMDIs). Particle size distributions of solution pMDIs containing hydrofluoroalkane-134a (HFA-134a) and ethanol were evaluated using 2 complementary particle-sizing methods: laser diffraction (LD) and cascade impaction (CI). Solution pMDIs were formulated from mixtures of HFA-134a (50%–97.5% wt/wt) and ethanol. A range of propellant concentrations was selected for a range of vapor pressures. The fluorescent probe, Rhodamine B, was included for chemical analysis. The complementary nature of LD and CI allowed identification of 2 dominant particle size modes at 1 and 10 μm or greater. Increasing propellant concentrations resulted in increases in the proportion of the size distributions at the 1-μm mode and also reduced the particle size of the larger droplet population. Despite significant spatial differences and time scales of measurement between the particle-sizing techniques, the fine particle fractions obtained from LD and CI were practically identical. This was consistent with LD experiments, which showed that particle sizes did not decrease with increasing measurement distance, and may be explained by the absence of significant evaporation/disintegration of larger droplets. The fine particle fractions (FPFs) emitted from HFA-134a/ethanol solution pMDI can be predicted on the basis of formulation parameters and is independent of measurement technique. These results highlight the importance of presenting particle size distribution data from complementary particle size techniques.     

A novel fiber-optic photometer for in situ stability assessment of concentrated oil-in-water emulsions

The purpose of this research was to evaluate a novel fiberoptic photometer for its ability to monitor physical instabilities occurring in concentrated emulsions during storage. For this, the fiber-optic photometer was used to measure transmission of oil-in-water emulsions stabilized with hypromellose (HPMC) as a function of oil volume fraction and droplet size distribution (DSD). To detect physical instabilities like creaming and coalescence, the transmissivity of the samples was studied at 2 different hight levels over a certain period of time. The corresponding droplet size distributions were determined by laser diffraction with PIDS. Transmissivity was found to depend on the number of dispersed droplets and thus is sensitive to both the variation of phase volume fraction as well as the emulsions droplet size distribution. At constant DSD, light transmission decreased linearly with increasing oil content within a large interval of phase volume fractions from 0.01 to 0.3. At constant phase volume fraction, an increase in droplet size increased light transmission. Investigation of creaming on emulsions with different droplet size distributions showed changes in the initial delay times and creaming velocities. In contrast to creaming phenomenon coalescence can be identified by height independent changes of the transmissivity. In conclusion, transmissivity of oil-in-water emulsions observed by the novel fiber-optic photometer is sensitive to phase volume fraction, droplet size distribution, and thus can be used as a tool for stability studies on concentrated emulsions. Published: August 31, 2007     

Determination of contact angle by molecular simulation using number and atomic density contours

The contact angles of Lennard-Jones fluid droplets on a structureless solid surface, simulated using Monte Carlo simulation, are calculated by fitting isochoric surfaces and making a number of assumptions about the droplet. The results show that there are significant uncertainties in the calculated contact angles due to the choice of these assumptions, such as the grid size used in tracking the isochoric density profile, the omission of isochoric data points near the surface and the function used to fit the isochoric profile. In this study, we propose a new method of calculating density contours based on atomic density instead of number density. This method results in a much smaller variation in contact angle when applying different assumptions than using number density for isochoric contours. The most consistent results, across a range of assumptions about the droplet and the contact angle, come from averaging the contact angle from several isochoric density profiles. In addition, this gives a measurement of the variation due to the choice of isochoric density.     

Effects of conidial densities and spray volume of Metarhizium anisopliae and Beauveria bassiana fungal suspensions on conidial viability,droplet size and deposition coverage in bioassay using a novel bioassay spray system

A newly developed spray tower was used to characterise droplet distribution and coverage of conidial suspensions of Metarhizium anisopliae ATCC 62176 and Beauveria bassiana NI8 with different spray volumes. ATCC 62176 and NI8 had different spray models which could be caused by the surface physicochemical characteristics of the strains and conidia.     

Estimation of the commercial height of trees with laser meter: a viable alternative for forest management in the Brazilian Amazon

Commercial height of the tree is a key variable for estimating the wood stock in tropical forests managed for timber production purposes. Most available measurement devices suffer limitations in this type of forest, promoting low precision measurements with high variation errors. The laser meter device appears as a viable alternative, as in addition to using trigonometric principles, it is not necessary that the device is close to the eyes of the meter to carry out the measurement. The device can be used to measure commercial height of trees on flat or sloping terrain, at different distances from the tree. However, there are no studies evaluating the precision of this device. The objective of this study was to determine the precision of the laser meter method for estimating the commercial height of trees, as compared to the actual measurement in a tropical forest in the Brazilian Amazon. Measurements were made on 300 trees with commercial height between 7 and 14 m. Actual commercial heights were measured with graduated ruler. Applied tests were paired t test, graphical analysis of residuals and calculations of bias statistics, mean absolute deviation, standard deviation of differences, and coefficient of determination (R²). Paired t test indicated that the mean of the heights measured by the laser meter is statistically equal to that of the graduated ruler. Measurements with laser meter did not show bias and had mean error of 0.0745. The standard deviation of the differences indicated dispersion of errors of 0.97, equal to that shown in the graduated rule. Laser meter presents an alternative method for estimating the commercial height of trees in tropical forest in the Brazilian Amazon. There was no tendency to underestimate or overestimate the commercial heights of trees. Use of the laser meter is potentially of use for measuring the commercial height of trees in tropical forests.     

Spray retention for liquid and mycoherbicide inoculum in three weed-biocontrol systems

Spray retention is often used to measure herbicide delivery to optimize application parameters, but little is known about retention characteristics of mycoherbicide inoculum applied for weed biocontrol. This study examined inoculum retention of three mycoherbicide agents, Pyricularia setariae, Colletotrichum truncatum and C. gloeosporioides f. sp. malvae, on their respective weed targets: green foxtail, scentless chamomile and round-leaved mallow. Conidium suspensions of these fungal pathogens containing a sodium-fluorescein tracer dye were applied at 500, 1000 and 2000 L ha^-1 using a cabinet sprayer, and the liquid volume and number of conidia retained on the plants were quantified. On all three weed species, liquid and conidium retention showed a high degree of correlation at varying application volumes although slight differences existed depending on the weed species. Based on the analysis of regression slopes, liquid retention reflected conidium retention most closely on green foxtail but slightly overestimated the number on scentless chamomile and round-leaved mallow, possibly due to different plant morphology and spray run-off at extremely high application volumes. Liquid retention can generally be used as an indicator in studying effects of spray quality on mycoherbicide retention for improved delivery and biocontrol in these weed-biocontrol systems.     

Can the theory of critical distances predict the failure of shape memory alloys?

Components made from shape memory alloys (SMAs) such as nitinol often fail from stress concentrations and defects such as notches and cracks. It is shown here for the first time that these failures can be predicted using the theory of critical distances (TCDs), a method which has previously been used to study fracture and fatigue in other materials. The TCD uses the stress at a certain distance ahead of the notch to predict the failure of the material due to the stress concentration. The critical distance is believed to be a material property which is related to the microstructure of the material. The TCD is simply applied to a linear model of the material without the need to model the complication of its non-linear behaviour. The non-linear behaviour of the material at fracture is represented in the critical stress. The effect of notches and short cracks on the fracture of SMA NiTi was studied by analysing experimental data from the literature. Using a finite element model with elastic material behaviour, it is shown that the TCD can predict the effect of crack length and notch geometry on the critical stress and stress intensity for fracture, with prediction errors of less than 5%. The value of the critical distance obtained for this material was L?=?90?μm; this may be related to its grain size. The effects of short cracks on stress intensity were studied. It was shown that the same value of the critical distance (L?=?90?μm) could estimate the experimental data for both notches and short cracks.     

Measuring lung function in mice: the phenotyping uncertainty principle.

Measuring lung function in mice is essential for establishing the relevance of murine models to human lung disease. However, making such measurements presents particular technical challenges due to the small size of the animal, particularly with regard to the measurement of respiratory flows. In this review, we examine the various methods currently available for assessment of lung function in mice and contrast them in terms of a concept we call the phenotyping uncertainty principle; each method can be considered to lie somewhere along a continuum on which noninvasiveness must be traded off against experimental control and measurement precision. Unrestrained plethysmography in conscious mice represents the extreme of noninvasiveness and is highly convenient but provides respiratory measures that are so tenuously linked to respiratory mechanics that they cannot be considered as meaningful indicators of lung function. At the other extreme, the measurement of input impedance in anesthetized, paralyzed, tracheostomized mice is precise and specific but requires that an animal be studied under conditions far from natural. In between these two extremes lie methods that sacrifice some precision for a reduction in the level of invasiveness, a promising example being the measurement of transfer impedance in conscious, restrained mice. No method is optimal in all regards; therefore, the appropriate technique to use depends on the application.     

The effect of air support on droplet characteristics and spray drift

Air assistance on field sprayers creates a forced airstream under the spray boom which blows the spray droplets into the crop. The advantages of this relative new technique are less drift of spray droplets and the possibility to reduce the amount of pesticides and spray Liquid. The purpose of this work was to investigate the effect of air assistance on the characteristics of spray droplets and their driftability. Based on air velocity measurements on an air assisted field sprayer, a system of air assistance was developed in addition to a laser-based measuring set-up for the characterisation of spray droplets. With this set-up, the effect of air support on the droplet characteristics was investigated for different settings of the air assistance. The effect on spray drift was quantified based on field drift measurements. A reducing effect on the total amount of spray drift was demonstrated for the Hardi ISO F 110 02, F 110 03 and LD 110 02 nozzles with drift reduction factors a(d) of, respectively, 2.08, 1.77 and 1.53. The use of air support had no significant effect for the LD 110 03 nozzles on the total amount of spray drift. Comparing droplet size and drift results, it was found that air support has the highest impact on the amount of spray drift for the finer sprays by increasing droplet velocities. The effect of air support on droplet sizes is rather limited.     

Real‐time droplet size analysis using laser micrometer as a process analytical technology tool for continuous dripping process

Process analysis and monitoring during the manufacturing of the dripping pills are essential. However, research on developing sensor‐based technology or process analytical technology (PAT) tools to analyze and monitor the dripping process is minimal. The purpose of this work is to develop a fast and non‐destructive laser detection system for quantitative visualization of droplets, which involves detecting the size of the droplet and calculating the weight of the dripping pills during the dripping process. Several factors influencing the detection performance of the detection system and the detection system capability for quantitation of the pill weight were explored. The laser detection system accurately detects the weight of the dripping pills with the coefficients of determination (R²) higher than 0.99. It was also robust concerning the variation in critical process parameters and critical material attributes. Furthermore, the laser detection system was successfully applied to the production line of Ginkgo biloba leaf dripping pills to monitor the dripping pills weight. The proposed laser detection system can analyze and monitor the dripping process in dripping pill manufacturing with stable performance, high accuracy, and high efficiency.     

Microorganism viability influences internal phase droplet size changes during storage in water-in-oil emulsions

Water-in-oil emulsions provide an alternative for long-term stabilization of microorganisms. Maintaining physical stability of the emulsion and cell viability is critical for large-scale application. Water-in-oil (W/O) emulsions were prepared with the biolarvacide Lagenidium giganteum and the green alga Chlorella vulgaris. Physical stability was measured via light scattering measurements of the internal phase droplets and cell viability was measured by plating and enumerating colony forming units. Emulsions were demonstrated to stabilize L. giganteum and C. vulgaris for more than 4 months without refrigeration. Introducing nutrients into the internal phase of W/O emulsions without cells had no significant effect on changes in aqueous phase droplet size dynamics. Internal phase droplet size changes that occurred over time were greater in the presence of cells. Increases in droplet size were correlated with cell death indicating measurement of internal phase droplet size changes may be an approach for monitoring declines in cell viability during storage.