Fabrication of amorphous pharmaceutical materials by electrospraying into reduced pressure

It is estimated that more than 95% of new drug candidates suffer from limited bioavailability [1]. Particle size reduction and formation of amorphous form are commonly used techniques in modifying bioavailability of such drugs. In the present study, electrospraying was used in drug particle production. Three poorly soluble drugs were electrosprayed. Particle size was reduced down to micrometre range. Electrospraying was carried out in both atmospheric and reduced pressure, the latter in order to increase the proportion of amorphous content. The aim of the study was to examine the degree of crystallinity of the produced particles for both pressures.     

Production of fibroin nanopowder through electrospraying

Fibroin is a biomaterial and in the powder form, has found applications such as food and cosmetic additive as well as drug delivery. Various methods have been employed to produce fibroin powder with different particle size range. In this study, a novel and original application of electrospraying technique capable of producing fibroin nanopowder is presented. Our technique is based on electrospraying of dilute fibroin solution in formic acid. Moreover, the effect of variables in electrospraying, namely, concentration of fibroin solution, voltage, feed rate, and needle–collector distance, on average particle size of fibroin nanopowder has been studied. The result of this study showed that electrospraying is capable of producing fibroin nanopowder with average particle size as low as 80 nm. In fact in comparison to other methods reported in the literature, electrospraying alongside with the precipitation method produce fibroin nanopowder with the lowest particle size. However, nanopowder obtained through electrospraying technique enjoys a more uniform spherical shape and size. As far as the variables are concerned, it was ascertained that lower concentrations, lower feed rates and longer needle–collector distances lead to a decrease in the average particle size of fibroin nanopowder. Increasing voltage up to 20 kV decreases the particle size; but with higher voltages the average particle size increases. FT-IR and XRD studies showed that the fibroin nanopowder has a β-sheets structure, similar to fibroin filaments but with a lower crystallinity index.     

Electrospraying route to nanotechnology: An overview

Electrospraying (electrohydrodynamic spraying) is a method of liquid atomization by means of electrical forces. In electrospraying, the liquid at the outlet of a nozzle is subjected to an electrical shear stress by maintaining the nozzle at high electric potential. The advantage of electrospraying is that droplets can be extremely small, in special cases down to nanometers, and the charge and size of the droplets can be controlled to some extent by electrical means, i.e., by adjusting the flow rate and voltage applied to the nozzle. Due to its properties, electrospraying is considered as an effective route to nanotechnology. The paper considers the latest achievements in micro- and nano-thin-film production, including self-assembled nanostructures, in solid nano-particle generation, and in the formation of micro- and nanocapsules.     

Monolayer deposition of L10 FePt nanoparticles via electrospray route

The deposition monolayers of L1₀ FePt nanoparticles via an electrospraying method and the magnetic properties of the deposited film were studied. FePt nanoparticles in a size of around 2.5 nm in diameter, prepared by a liquid process, were used as a precursor. The size of the deposited particles can be controlled up to 35 nm by controlling the sprayed droplet size that is formed by adjusting the precursor concentration and the precursor flow rate. The droplets were heated in a tubular furnace at a temperature of up to 900 °C to remove all organic compounds and to transform the FePt particles from disordered face centered cubic to an ordered FCT phase. Finally, the particles were deposited in the form of a monolayer film on a silicon substrate by electrostatic force and characterized by scanning electron microscopy. The monolayer of particles was obtained by the high charge on particles obtained during the electrospraying process. The magnetic properties of the monolayer were investigated by magneto-optic Kerr effect measurements. Coercivity up to 650 Oe for a film consisting of 35 nm L1₀ FePt nanoparticles was observed after heat treatment at a temperature of 800 °C.     

A Method for Increasing the Sensitivity of Phase Doppler Interferometry to seed particles in liquid spray flows

A method has been developed to increase the sensitivity of phase Doppler interferometry-based particle sizing systems to small particles in the presence of a spray containing large and small droplets; an important consideration when using seed particles to track the gas-phase velocity in multi-phase flows. The method, applicable to PDPA systems configured to operate in first and higher order refraction mode, involves doping the sprayed liquid with a dye that is strongly absorbing at the incident laser wavelengths. This results in greatly diminished scattered intensity from larger droplets, thus allowing the photomultiplier gain to be set to a level sufficient to easily detect small particles without saturation. Tests conducted indicate that, at a collection angle of 30° and droplet absorptivity of γ = 0.014/μm, the PDPA can accurately size absorbing droplets up to approximately 200 μm. This upper limit can be extended by changing selection angle. Tests performed with an actual spray demonstrated that the method allowed detection of 1 μm to 235 μm droplets; more than four times the instrument's usual range of 50: 1. A data correction scheme to determine the effective probe volume radius for each particle size class has been developed for absorbing particles, as standard correction schemes derived for non-absorbing droplets excessively weigh distributions toward smaller particles.     

Preparation of nanoparticles of poorly water-soluble antioxidant curcumin by antisolvent precipitation methods

The objective of this study was to enhance the solubility and dissolution rate of a poorly water-soluble antioxidant, curcumin, by fabricating its nanoparticles with two methods: antisolvent precipitation with a syringe pump (APSP) and evaporative precipitation of nanosuspension (EPN). For APSP, process parameters like flow rate, stirring speed, solvent to antisolvent (SAS) ratio, and drug concentration were investigated to obtain the smallest particle size. For EPN, factors like drug concentration and the SAS ratio were examined. The effects of these process parameters on the supersaturation, nucleation, and growth rate were studied and optimized to obtain the smallest particle size of curcumin by both the methods. The average particle size of the original drug was about 10–12 μm and it was decreased to a mean diameter of 330 nm for the APSP method and to 150 nm for the EPN method. Overall, decreasing the drug concentration or increasing the flow rate, stirring rate, and antisolvent amount resulted in smaller particle sizes. Differential scanning calorimetry studies suggested lower crystallinity of curcumin particles fabricated. The solubility and dissolution rates of the prepared curcumin particles were significantly higher than those the original curcumin. The antioxidant activity, studied by the DPPH free radical-scavenging assay, was greater for the curcumin nanoparticles than the original curcumin. This study demonstrated that both the methods can successfully prepare curcumin into submicro to nanoparticles. However, drug particles prepared by EPN were smaller than those by APSP and hence, showed the slightly better solubility, dissolution rate, and antioxidant activity than the latter.     

A PMMA optical diffuser fabricated using an electrospray method

To coat microsized poly(methyl methacrylate) (PMMA) particles of uniform size and density on poly(ethylene terephthalate) (PET) films, we introduce an electrospraying technique that uses a target electrode applied with an ac electric field. Using the apparatus and various material properties, we could achieve good collection and a uniform size distribution of hemispherical droplets on the PET film. The optical properties, transmittance, and light diffusivity of the films electrosprayed with the PMMA were characterized and the sprayed particles appear to act as a good optical diffuser, like microlenses. PACS 47.65.-d; 42.70.Jk; 81.15.-z     

Dynamics of drying in 3D porous media

The drying dynamics in three dimensional porous media are studied with confocal microscopy. We observe abrupt air invasions in size from single particle to hundreds of particles. We show that these result from the strong flow from menisci in large pores to menisci in small pores during drying. This flow causes air invasions to start in large menisci and subsequently spread throughout the entire system. We measure the size and structure of the air invasions and show that they are in accord with invasion percolation. By varying the particle size and contact angle we unambiguously demonstrate that capillary pressure dominates the drying process.     

Particle Formation from Single Droplets of Aqueous Solutions of Lead Nitrate

The thermal evolution of droplets of aqueous solution of lead nitrate was studied in a drop-tube furnace, which simulates typical conditions for material synthesis, through spray pyrolysis, and for the thermal destruction of liquid-containing waste. The processes of droplet evaporation, precursor precipitation within the droplet and thermolysis of the precipitated particles were followed by means of the spectral analysis of the ultraviolet light scattered by the aerosol produced during the heating of aqueous droplets (100 μm) of lead nitrate, with different salt concentrations, from ambient temperature up to 1200 K. Dimensions and physico-chemical properties of the droplets/particles were obtained in situ by means of ultraviolet spectra of light scattering (UVSLS) and compared with scanning electron microscopy (SEM) of the sampled material. A plasma generated in the air by an optical breakdown induced by a Nd:YAG laser was employed as the light source in the wavelength range 200–400 nm, thus allowing an exceptionally high photon flux in the ultraviolet region where intense and species-specific interactions with metal species take place. The spray drying process was followed by measuring the light transmitted by the droplets in the backward region. As the drying process progresses, the surface concentration reaches a saturation value and solute is deposited as a solid phase forming a surface crust, which grows steadily. At this point in the process of droplet drying, information was retrieved from the light reflected by the particle interface. Two spectral scattering behaviors were detected at temperatures above the salt precipitation within the droplet. On the basis of Mie calculations and SEM measurements, these behaviors were attributed to lead nitrate particles with typical diameters of the residual droplets (about 50 μm) and to micrometer-sized lead oxide particles. The effect of salt concentration on the drying process and the thermolysis of lead nitrate to oxide was investigated by changing the salt concentration from very dilute conditions up to almost the saturation concentration.     

An electrosprayed coating process for fabricating hemispherical PMMA droplets for an optical diffuser

A modified electrospraying process is proposed for fabricating uniform microsized poly(methyl methacrylate) (PMMA) hemispherical droplets on poly(ethylene terephthalate) films for use as optical diffusers. In this process, an electrode controlled by an electric field is attached to a rotating collector, and various electric field conditions are applied to the droplets ejected from a positively charged nozzle. The distribution of small hemispherical droplets and the surface roughness resulting from this modified electrospraying process are more uniform than those achieved in the normal electrospraying process. The frequency of the field applied to the electrode is not critical to the production of stable PMMA droplets. The optical diffusivity of the PMMA film fabricated using this process is greater than that of normally fabricated film, demonstrating the feasibility of using this process to create newly designed optical diffusers.     

Constraints of two-colour TiRe-LII at elevated pressures

The main objective of this work is to investigate the influence of high-pressure conditions on the determination of primary particle size distributions of laser-heated soot particles using pyrometrically determined temperature decays. The method is based on time-resolved laser-induced incandescence measurements carried out at two different wavelengths (two-colour TiRe-LII). The LII signals are transferred into a particle ensemble averaged (effective) temperature using Planck’s thermal radiation formula. Assuming that all particles within the size distribution possess a unique temperature at the end of the laser pulse, the size distribution can be determined by numerically simulating the measured temperature decay. From our investigations, for pressures up to a few bars it is obvious that this strategy can be successfully applied if standard laser pulses of nano-second duration are used as an LII-excitation source. At higher pressures the time scales of heat conduction are decreased to such an extent that a unique temperature for all particles within the ensemble cannot be assumed at the end of the nano-second laser pulse. However, further investigations show that the presented two-colour TiRe-LII technique can be successfully adopted under technical high-pressure conditions as well, if the pulse duration of the TiRe-LII-excitation source is reduced into the pico-second range.     

溶液液滴蒸发变干的环状沉积

液体蒸发驱动的颗粒自组装现象在许多的工业技术中有重要应用. 本文利用显微镜观测含有颗粒物质的液滴变干后留在固体表面的颗粒形成的环状沉积图案. 采用微米粒径的SiO₂小球水溶液液滴蒸发变干模拟咖啡环的形成过程, 结果发现液滴蒸发过程中接触线的钉扎是环状沉积的必要条件. 在液滴蒸发过程中颗粒随着补偿流不断的向液滴边缘移动, 聚集在接触线处形成环. 液滴蒸发变干后残留在液滴内部的颗粒数随颗粒质量分数的增加而增加, 可以达到单层的颗粒排列. 而玻璃衬底上的颗粒环在颗粒质量分数很小时, 形成单层排列, 且一排一排地生长. 蒸发过程中颗粒环由于液滴边缘的尺寸限制向液滴中心缓慢移动. 这会导致液滴中不同大小颗粒的分离. 关键词： 液滴 接触线 蒸发 颗粒     

Modeling effective viscosity reduction behaviour of solid suspensions

Under a simple shearing flow, the effective viscosity of solid suspensions can be reduced by controlling the inclusion particle size or the number of inclusion particles in a unit volume. Based on the Stokes equation, the transformation field method is used to model the reduction behaviour of effective viscosity of solid suspensions theoretically by enlarging the particle size at a given high concentration of particles. With a lot of samples of random cubic particles in a unit cell, our statistical results show that at the same higher concentration, the effective viscosity of solid suspensions can be reduced by increasing the particle size or reducing the number of inclusion particles in a unit volume. This work discloses the viscosity reduction mechanism of increasing particle size, which is observed experimentally.     

Multi-nozzle electrospray system for gas cleaning processes

A multi-nozzle electrospray system was developed as a charged droplet source for cleaning a gas contaminated with fine particles. The efficiency of removal of fine particles from the gas can be significantly increased, as compared to uncharged sprays, when the droplets are electrically charged. In the presented experiments, the spray of the droplets of size lower than 100 μm was charged either positively or negatively. Cigarette smoke was used as a source of submicrometer particles. The suppression of the particle concentration was determined after different time intervals of spraying of water. Further improvement in gas cleaning was obtained after charging the smoke particles using a specially designed corona charger. The efficiency of the cleaning process was similar to that obtained for droplets generated by mechanical atomisers with induction charging, but the electrospraying allowed decreasing the water consumption up to about three times.     

自悬浮定向流技术中铜纳米微粒的粒度控制研究

 采用自悬浮定向流技术制备了金属铜纳米微粒，根据TEM的行貌像对样品平均粒度进行标定，并结合样品制备的条件对制备工艺进行了研究。结果表明，自悬浮定向流技术可以方便地制备出不同粒度的金属铜纳米微粒，微粒平均粒径随熔球温度的降低而减小，随冷却气体流速的增大而减小；在1 200℃下微粒平均粒径随惰性气体压强的增大而减小，而在1 300℃时惰性气体压强对微粒平均粒径的影响不再具有规律性。     

Non‐Spherical 2‐Dimensional Particle Size Analysis from Chord Measurements using Bayes' Theorem

A method of deconvoluting 2‐dimensional particle size distributions from chord size data is presented and evaluated. This is the Probability Apportioning Method (PAM3). It assumes that the particles (or droplets) can be represented by super quadrics and are cut randomly by a sensor to give a chord measurement. Starting from an assumed uniform particle distribution, Bayes' theorem is used to calculate hit probabilities for each particle type and the population is then recalculated. The process is then repeated until there is no significant further change in the calculated distribution. Using numerical simulations PAM3 is shown to be quite accurate and robust for a number of different types of particle shapes provided there is a sufficient number of accurate measurements.     

Measurement of the Density of Polymeric Nanoparticulate Drug Carriers by Isopycnic Centrifugation

The development of polymer nanoparticles as drug carriers requires numerous steps including several in vitro evaluations in cell cultures and biocompatibility. To perform these experiments, it is crucial to express the particle concentration as the number of particles per volume unit or as the particle surface area. Calculation of these suspension characteristics can be perfomed knowing the size and the density of the nanoparticles as well as the polymer concentration. While particle size and polymer concentration are parameters being determined routinely, this study proposes to measure the density of the nanoparticle drug carriers by isopycnic centrifugation using linear sucrose gradients. The method was found to be very reproducible and it presents the advantage of being applied on a small sample of nanoparticles.     

In-Line Particle Size Determination for Jet Agglomeration Processes

In jet agglomeration plants, powders are agglomerated to obtain good instant properties. The free-falling initial material is wetted in a spray cone by droplets or in a steam jet by condensation at the particle surface. In a subsequent region of high particle concentration, collision between particles occurs and agglomerates form, if the forces of adhesion are strong enough. A commercial measurement device, working according to the principle of Fraunhofer diffraction, was modified for in-line application. It was used to measure particle size distributions and concentrations of solid particles and droplets in jets. A model is presented to calculate local particle sizes by means of mass balances from integral measurements over large volumes. The results of in-line particle size and agglomerate size analyses show the practical importance of dry agglomeration during transport and lead to a better understanding of the subsequent wet agglomeration process.     

Numerical study on the desorption processes of oil droplets inside oil-contaminated sand under cavitation micro-jets

The removal of the adsorbed oil droplet is critical to deoiling treatment of oil-bearing solid waste. Ultrasonic cavitation is regarded as an extremely useful method to assist the oil droplets desorption in the deoiling treatment. In this paper, the effects of cavitation micro-jets on the oil droplets desorption were studied. The adsorbed states of oil droplets in the oil-contaminated sand were investigated using a microscope. Three representative absorbed states of the oil droplets can be summarized as: (1) the individual oil droplet adsorbed on the particle surface (2) the clustered oil droplets adsorbed on the particle surface; (3) the oil droplet adsorbed in a gap between particles. The micro-jet generation during the bubble collapse near a rigid wall under different acoustic pressure amplitudes at an ultrasonic frequency of 20 kHz was investigated numerically. The desorption processes of the oil droplets at the three representative absorbed states under micro-jets were also simulated subsequently. The results showed that the acoustic pressure has a great influence on the velocity of micro-jet, and the initial diameter of cavitation bubbles is significant for the cross-sectional area of micro-jets. The wall jet caused by a micro-jet impacting on the solid wall is the most important factor for the removal of the absorbed oil droplets. The oil droplet is broken by the jet impinging, and then it breaks away from the solid wall due to the shear force generated by the wall jet. In addition to a higher sound pressure, the cavitation bubble at a larger initial diameter is more important for the desorption of the clustered oil droplets. Conversely, the micro-jet generated by the cavitation bubble at a smaller initial diameter (0.1 mm) is more appropriate for the desorption of the oil droplet in a narrow or sharp-angled gap.     

Investigation of airborne nanopowder agglomerate stability in an orifice under various differential pressure conditions

The stability of agglomerates is not only an important material parameter of powders but also of interest for estimating the particle size upon accidental release into the atmosphere. This is especially important when the size of primary particles is well below the agglomerate size, which is usually the case when the size of primary particles is below 100 nm. During production or airborne transportation in pipes, high particle concentrations lead to particle coagulation and the formation of agglomerates in a size range of up to some micrometers. Binding between the primary particles in the agglomerates is usually due to van der Waals forces. In the case of a leak in a pressurized vessel (e.g. reactor, transport pipe, etc.), these agglomerates can be emitted and shear forces within the leak can cause agglomerates to breakup. In order to simulate such shear forces and study their effect on agglomerate stability within the airborne state, a method was developed where agglomerate powders can be aerosolized and passed through an orifice under various differential pressure conditions. First results show that a higher differential pressure across the orifice causes a stronger fragmentation of the agglomerates, which furthermore seems to be material dependent.