Search

The release of drugs from poly(lactic-co-glycolic acid) (PLGA) microparticles depends to a large extent on the porosity of the particles. Therefore, porosity determination of PLGA microparticles is extremely important during pharmaceutical product development. Currently, mercury intrusion porosimetry (MIP) is widely used despite its disadvantages, such as the need for a large amount of sample (several hundreds of milligrams) and residual toxic waste. Here, we present a method based on the estimation of the volume of a known mass (a few milligrams) of particles using micro-flow imaging (MFI) to determine microparticle batch porosity. Factors that are critical for the accuracy of this method (i.e., density of the suspending fluid, particle concentration, and postsample rinsing) were identified and measures were taken to minimize potential errors. The validity of the optimized method was confirmed by using nonporous polymethylmethacrylate microparticles. Finally, the method was employed for the analysis of 7 different PLGA microparticle batches with various porosities (4.0%-51.9%) and drug loadings (0%-38%). Obtained porosity values were in excellent agreement with the MIP-derived porosities. Altogether, the developed MFI-based method is a valuable tool for deriving the total volume of a known mass of PLGA particles and therewith their porosity.

This works investigates the possibility of using Acoustic Emissions (AE) to estimate the Particle Size Distribution (PSD) of a mixture of particles that comprise of particles of different densities and geometry. The experiments carried out involved the mixture of a set of glass and polyethylene particles that ranged from 150-212 microns and 150-250microns respectively and an experimental rig that allowed the free fall of a continuous stream of particles on a target plate which the AE sensor was placed. By using a time domain based multiple threshold method, it was observed that the PSD of the particles in the mixture could be estimated.

The performance of a novel microfluidic impedance cytometer (MIC) with coplanar configuration is investigated in silico. The main feature of the device is the ability to provide accurate particle-sizing despite the well-known measurement sensitivity to particle trajectory. The working principle of the device is presented and validated by means of an original virtual laboratory providing close-to-experimental synthetic data streams. It is shown that a metric correlating with particle trajectory can be extracted from the signal traces and used to compensate the trajectory-induced error in the estimated particle size, thus reaching high-accuracy. An analysis of relevant parameters of the experimental setup is also presented.

In this work, time-resolved laser-induced incandescence (TiRe LII) has been employed to measure primary particle diameters of soot in an atmospheric laminar ethylene diffusion flame. The generated data set complements existing data determined in one single location and takes advantage of the good spatial resolution of the ICCD detection. Time resolution is achieved by shifting the camera gate along the LII decay. One key input parameter for the analysis of time-resolved LII is the local flame temperature. This was determined on a grid throughout the flame by coherent anti-Stokes Raman scattering. The accurate temperature data, in combination with other published data from this flame, are well suited for soot model validation purposes while we showed feasibility of a shifted gate approach to deduce 2D particle sizes in the chosen standard flame. © 2013 Springer-Verlag Berlin Heidelberg.

An interferometric imaging technique has been proposed to instantly measure the diameter of individual spherical dust particles suspended in a gas discharge plasma. The technique is based on the defocused image analysis of both spherical particles and their binary agglomerates. Above a critical diameter, the defocused images of spherical particles contain stationary interference fringe patterns and the fringe number increases with particle diameters. Below this critical diameter, the particle size has been measured using the rotational interference fringe patterns which appear only on the defocused images of binary agglomerates. In this case, a lower cut-off limit of particle diameter has been predicted, below which no such rotational fringe patterns are observed for the binary agglomerates. The method can be useful as a diagnostics for complex plasma experiments on earth as well as under microgravity condition.

As environmental awareness raises the expectations to reduce emission of modern diesel engines are growing as well. Fuel diversity and the advanced injector systems requires even more attention on an ever existing problem which is called nozzle hole fouling. Recent literature and observations at Scania indicate the phenomena is connected to fuel filter plugging caused by metal carboxyl contaminants through the formation of “soft particles”. This report begins with a literature review about the nature of agglomerates in biodiesel. Followed by the evaluation of six particle sizing equipment. This include one ensemble technique based on Brownian motion, namely dynamic light scattering. The remaining five techniques are single particle counters, including a high speed camera system, light blocking system, Nano tracking analysis and two different approaches using light microscope. To characterise the structure and chemical components of the particles SEM, EDX, FT-IR and ICP-OES were used. From the above mentioned methods optical microscopy was chosen to be the best method to evaluate the particle distribution. The main reasons for this is the ability to measure particles in the solution in the desired size range and the possibility to couple it with a Raman spectrometer, providing possibilities for future studies. Besides finding the best technique to measure the particles, a secondary result is the negation of Zinc-neodecanoate creating particles in the fuel. It opposes the assumption made in the literature about filter blocking, and it finds the need for deeper understanding of the nature of soft particles.

Recovering the size distribution of aerosolized soot aggregates from multiangle elastic light scattering data requires the inversion of an integral equation, which is a mathema- tically ill-posed problem. This paper demonstrates how maximum a posteriori (MAP) inference can be used to stabilize the inversion by introducing prior information about the size distribution of the soot aggregates. Results show that the size distribution can be recovered using only simple smoothness and non-negativity priors if the aggregate number density is known, but otherwise it is necessary to specify additional information about the presumed distribution shape.

It is important to have correct information regarding particle size in order to interpret, control, and optimize many industrial processes. Prior to the recent advent of acoustic attenuation spectroscopy, it was difficult to study particle size distribution online and under real process conditions in processes involving concentrated dispersions (suspensions or emulsions). The technique still needs improvement because it is less known how and under which conditions to employ the technique when dispersions involve impurities that could be soluble, insoluble, in the form of additives, and so on. This lack of understanding has almost halted the advancement in applications of the technique to various processes that essentially involve dispersions with impurities. This study investigates aqueous suspensions of CaCO3 at different concentrations (i.e., 5%, 10% and 20% mass/mass) with added impurities of MgCO3 (insoluble impurity), NaNO3 (soluble impurity) and sodium polyacrylate (soluble additive) at varying proportions (5%, 10%, 20% and 30% of the weight of CaCO3). The study characterizes and compares dispersion with and without impurity in order to demonstrate the possible ways in which addition of an impurity change the original acoustic attenuation spectrum of a dispersion. The study brings the conditions in which acoustic attenuation spectroscopy is capable of explaining that addition of an impurity will not change original particle size of the disperse medium.

The use of colloidal systems in pharmaceutical formulations, for addressing the issue of selective and controlled drug delivery or for improving drug availability, requires an accurate previous characterization of their chemical and physical properties. Light scattering is a useful and non-invasive method to study the structure and conformation of colloids in a wide space-scale, encompassing nanometric- to micrometric-sized particles, as well as their size distribution, surface electrostatic potential and aggregation phenomena occurring under proper conditions. In this review the physical bases of the light scattering approach are described and many examples are reported to discuss the examination of various multiphase systems useful in pharmaceutical fields.

The purpose of the present research is to develop and apply an experi- mental technique for measuring the size of nanoparticles and nanodroplets in a flow environment. The developed non-intrusive, optical method is called Light Extinction Spectroscopy (LES) and it allows to determine the size of particles from measuring their light transmission spectrum on the Ultraviolet-Near-Infrared range. The most crucial part of the develop- ment work is to obtain a reliable data processing method, which is based on the regularized solution of an ill-conditioned inverse problem. The de- veloped method is first tested using synthetic data, which allows to deter- mine the measurement range and also the measurement errors caused by various sources. This is followed by performing laboratory experiments for validating the LES technique. Validation measurements using calibrated particles and a reference instrument shows that sizing errors are in the order of 5-10%. Afterwards, the technique is applied for characterizing the Brownian coagulation process of nanodroplets, where the growth rate of droplets is successfully measured and is found to agree with theoreti- cal expectations. Next, the LES technique is applied to coagulating solid particles, where the growth rate of these complex non-spherical objects is retrieved. Finally, a particle monolayer is deposited on an air-water inter- face and it is shown that the LES technique can retrieve the particle-water contact angle, which allows the characterization of nanoparticle wettabil- ity and the study of the related interesting physical phenomena., Doctorat en Sciences de l'ingénieur et technologie, info:eu-repo/semantics/nonPublished

Dust nanoparticles metrology has become a major scientific and industrial issue in order to control the characteristics of nano-objects (size, density, etc.). For industrial interests it concerns processes control and monitoring, manufactured products quality, human being and environment protection. It is therefore, crucial to find innovative methods of characterization and easy to implement and to handle. The objective of this research program was to develop and optimize solutions for characterizing nanoparticles in dry process and environment using a plasma (promoting disagglomeration of the studied powders). The presence of nanoparticles substantially altering the electrical characteristics of the plasma, we have, at first, developed a diagnostic based on the electrical characteristics of the discharge and the plasma. This method allows the determination the average nanoparticles size and concentration trapped in the plasma gas phase. Then, in a second step, we developed a diagnostic based on multi-angle laser light scattering, allowing us to get the size and the average density of the nanoparticles in the plasma, but also their refractive index. We finally focused our interest on the optimization of the plasma-assisted sedimentation of nanoparticles to obtain their size distribution especially for particles having sizes below 10 nm. The correlation of these three diagnostics gives us, so an efficient and reliable diagnostic for the global characterization in terms of size, density and optical properties of nanoparticles trapped in the plasma., La métrologie des nanoparticules est devenue un enjeu scientifique et industriel capital pour pouvoir contrôler les caractéristiques des nano-objets (taille, densité, etc.) dans les procédés industriels tant pour la qualité des produits fabriqués que pour la protection des personnes et de l’environnement. Il est important, par conséquent, de trouver des méthodes de caractérisation innovantes et simples à mettre en oeuvre. L’objectif de ce travail de recherche fût de développer et d’optimiser des solutions pour caractériser des nanoparticules en voie sèche à l’aide d’un plasma (favorisant la désagglomération de l’échantillon de poudres à étudier). La présence de nanoparticules modifiant sensiblement les caractéristiques électriques du plasma, nous avons, dans un premier temps, développé un diagnostic basé sur la caractérisation électrique de la décharge et du plasma. Cette méthode nous renseignant sur la taille et la densité moyenne des nanoparticules. Puis, dans un second temps, nous avons développé un diagnostic basé sur la diffusion multi-angle de la lumière laser, nous permettant d’obtenir, là aussi, la taille et la densité moyenne des nanoparticules présent dans le plasma mais également leur indice de réfraction. Nous nous sommes, enfin, intéressés à la sédimentation assistée par plasma permettant d’obtenir la distribution en taille des nanoparticules, en l’optimisant. La corrélation de ces trois diagnostics nous donne, donc, un diagnostic efficace et fiable permettant la caractérisation en taille, en densité et en propriétés optiques des nanoparticules piégées dans le plasma.

Insulin glargine (Lantus®, Aventis Pharma, Deutschland, GmbH) is a new long-acting human insulin analog. Structural modification of the insulin molecule at two sites alters its pH, causing insulin glargine to precipitate in the neutral environment of subcutaneous tissue and to form a depot that is slowly absorbed into the bloodstream. In this paper insulin glargine aggregation is investigated by light scattering. This study shows that, in a physiologic-like pH (even at low ionic strength) conditions, aggregation phenomena occur, giving rise to compact structures with radius of hundreds of nanometers. The aggregation of insulin glargine can be responsible for its slow in situ absorption allowing for a more controlled release.

International audience; Information concerning the aggregation state of fine solid particles is an important element for process control and monitoring of product quality in many applications of industrial slurries. This work deals with the application of different in-line methods to the characterization of silica aggregate size and morphology. All of these methods exploit turbidity signals, obtained by various means including: from analysis of turbidity fluctuations in homogeneous suspension and from overall turbidity decrease during particle settling. This work also presents the opportunity to report progress in morphological and optical models of small aggregates. As a result of these models, the morphological characteristics of the aggregates along with the number of their constituting particles are derived from experimental results. Similarities between the different methods are examined and discussed.

A novel polarized-type phase Doppler method is proposed for simultaneous measurements of particle size, velocity and refractive index on the basis of. the phases of two polarized Doppler beat signals in a single scattering direction. Light scattered by a moving particle in a certain direction is divided into two rays, which are then detected with different polarization angles to transmit dominantly reflected or refracted rays. Signal phases of these two rays are measured with respect to the phase of beat signal obtained by the reference detector. The particle diameter can be determined from the phase of reflected ray, whereas the particle refractive index can be obtained from the phase ratio of reflected and refracted rays. We carried out numerical computations and experiments to confirm the usefulness of the proposed method for simultaneous measurements of the particle size and refractive index.

A non-intrusive particle sizing method with a high spatial distribution is utilized for the estimation of cloud droplet spectra during flight test campaigns. The Interferometric Laser Imaging for Droplet Sizing (ILIDS) method derives particle diameters of transparent spheres by evaluating the out-of-focus image patterns. This sizing approach requires a polarized monochromatic light source, a camera including objective lens with a slit aperture, a synchronization unit and a processing tool for data evaluation. These components are adapted to a flight test environment to enable the microphysical investigation of different cloud genera. The herewith presented work addresses the ILIDS system design and specifications, the flight test preparation and selected results obtained in the lower and middle troposphere. The research platform was a commuter aircraft of type Dornier Do228-101 of DLR Flight Operation Center in Braunschweig. It was equipped with the required instrumentation including a high energy laser as light source. A comprehensive data set of around 71.800 ILIDS images was acquired over the course 5 flights. The data evaluation of the characteristic ILIDS fringe patterns relies among others on a relationship between the fringe spacing and the diameter of the particle. The simplest way to extract this information from a pattern is by fringe counting, which is not viable for such an extensive amount of data. A brief contrasting comparison of evaluating methods based on frequency analysis by means of Fast Fourier Transform (FFT) and on correlation methods such as Minimum Quadratic Difference (MQD) is used to encompass the limits and accuracy of the ILIDS method for such applications.

This report describes the certification of SRM 1962, a NIST Standard Reference Material for particle diameter. It consists of an aqueous suspension of monosize 3 (μm polystyrene spheres. Two calibration techniques were used: optical microscopy and electron microscopy. The first one gave a mean diameter of D¯=2.977±0.011 μm and a standard deviation of the size distribution σD = 0.020 μm, based on measurement of 4600 spheres. The second technique gave D¯=2.990±0.009 μm, based on measurement of 120 spheres. The reported value covering the two results is D¯=2.983 μm with a maximum uncertainly of 0.016 μm, with σD=0.020 μm.

The need to monitor, measure, and control sub-visible proteinaceous particulates in biopharmaceutical formulations has been emphasized in recent publications and commentaries. Some of these particulates can be highly transparent, fragile, and unstable. In addition, for much of the size range of concern, no practical measurement method with adequate sensitivity and repeatability has been available. A complication in measuring protein particulates in many formulations is the simultaneous presence of other particle types such as silicone micro-droplets, air bubbles, and extrinsic contaminants. The need has therefore been identified for new analytical methods which can accurately measure and characterize sub-visible particulates in formulations. Micro-flow imaging has been shown to provide high sensitivity in detecting and imaging transparent protein particles and a unique capability to independently analyze such populations even when other particle types are present.

Experimental, theoretical, and calculational details are presented for the three independent micrometrology techniques used to certify the mean diameter of Standard Reference Materisd 1960, nominal 10 μm diameter polystyrene spheres ("space beads"). The mean diameters determined by the three techniques agreed remarkably well, with all measurements within 0.1% of each other, an unprecedented achievement in the dimensional metrology of microspheres. Center distance finding (CDF), a method based on optical microscopy, gave a value of 9.89 ± 0.04 μm, which was chosen to be the certified mean diameter. The supporting measurements were done using metrology electron microscopy (MEM) and resonance light scattering (RLS). The MEM technique, based on scanning electron microscopy, yielded 9.89±0.06 μm for the mean diameter of the microspheres in vacuum, while the RLS value was 9.90 ±0.03 μm for the microspheres in liquid suspension. The main peak of the diameter distribution for SRM 1960 is nearly Gaussian with a certified standard deviation of 0.09 μm, as determined by CDF. Off the main peak, there are about 1% oversized particles and a negligible amount of undersized particles. The report gives a detailed description of the apparatus, the experimental methods, the data-reduction techniques, and an error analysis for each of the micro-metrology techniques. A distinctive characteristic of this SRM is that it was manufactured in microgravity aboard the NASA space shuttle Challenger and is the first commercial product to be made in space.

Optical coherence tomography was used to collect cross-sectional images of glass powder beds consisting of microspheres with diameters ranging from 8 to 175 µm. Images were formed by a collection of individual interferogram envelopes that give the backscattered light amplitude as a function of the optical path in the glass powder bed. The diameter distribution, for microspheres located near the surface of the beds, is obtained by appropriate peak distance measurements on threshold-selected envelopes after having performed the surface profilometry. The measured distributions are in good agreement with those obtained by laser diffraction. When considering the whole powder volume, the evaluation of the mean light penetration depth inside the powder beds proves to be a useful approach to evaluate the mean particle diameter, although no information is obtained on the actual particle size distribution in this case. Two simplified models are introduced to understand the linear relationship observed between the penetration depth and the mean particle size.

The objective of this work is to quantify the accuracy and precision of particle sizing performed through light scattering goniometry. A rigorous characterization of this simple method depends on a complete description of the scattering geometry, and to our knowledge this has not yet been done. We have determined the central diameter (d0) and standard deviation (σ) of samples of polystyrene spheres with a narrow normal distribution of diameters through a χ2 fit to the light scattering phase function. The fit is performed simultaneously in the variables d0 and σ. The model for the fit includes Mie scattering calculations, integration of the phase function over a normal distribution of diameters and a complete description of the scattering geometry. Experimental tests on spheres with diameters between 2 and 7 μm show that this method provides excellent accuracy and precision for the determination of d0 and good accuracy for the determination of σ. The precision in σ is poor in relative terms but in absolute terms it is around 0.05 μm within the range of sizes tested. We calculate the uncertainty limits for the determination of d0 and σ and show that they are consistent with all the supplier values except the value of σ for the 2 μm spheres, where aggregation was detected by optical microscopy. Other topics included in this work are: (i) comparison between our method and the classical simple fit through a pure monodisperse system (σ = 0); and (ii) dependence of the quality of sizing on the angular range of the measurement. Finally, comparison with published results shows that simple goniometry may outperform more complex methods.

Im Rahmen der Arbeit wurde ein Verfahren zur Bestimmung der Partikelgrößenverteilung unter Bedingungen entwickelt und realisiert, wie sie bei industriellen Syntheseprozessen von Pulvern vorherrschen. Die Partikelgrößen sind im submikronen Bereich. Die Prozessbedingungen, die das Messen von Partikelgrößenverteilungen behindern sind subatmospherische Drücke, hohe Partikelanzahlkonzentrationen, die Anwesenheit von Salzsäure sowie hohe Temperaturen und schwankende Drücke. Das zu Grunde liegende Messprinzip ist die differentielle Mobilitätsanalyse, die auf dem Bestimmen der Geschwindigkeit geladener Partikel in einem elektrischen Feld beruht. Das Prinzip ist für das Messen von Partikelgrößenverteilungen nanoskaliger gasgetragener Partikel (Aerosole) unter Laborbedingungen etabliert. Das Ziel der Arbeit war, das Verfahren so zu verändern, dass Messungen unter den oben genannten Bedingungen möglich sind. Die Tauglichkeit war an verschieden Prozessen zu zeigen. Alle hauptsächlichen Operationen des Messsystem sind von Veränderungen in Hinblick auf Prozesstauglichkeit betroffen: 1. Probenahme, 2. elektrische Aufladung der Partikel, 3. Fraktionierung im elektrischen Feld, 4. Konzentrationsmessung nach der Fraktionierung. Die dazu notwendigen Komponenten wurden mit Ausnahme der Aufladung neu entwickelt und im Labor untersucht. Zur elektrischen Aufladung wird eine UV Bestrahlungseinheit verwandt. Sie birgt gegenüber der Aufladung mit einem β-Strahler nicht die Gefahr radioaktiver Kontamination. Der Grad der Aufladung hängt jedoch vom Partikelmaterial, von der Partikelgröße, vom Trägergas, seiner Temperatur und seinem Druck ab. Die Aufladung wurde durch ein mathematisches Modell beschrieben, das für die jeweiligen Messbedingungen numerisch gelöst wurde. Die Komponenten wurden zu einem kompakten Gerät zusammengefügt, das durch neu entwickelte Software und Schnittstellen von einem PC gesteuert wird. Ein großes Augenmerk liegt auf der Überführung des rohen Messsignals in die Partikelgrößenverteilung, die unter Berücksichtigung der Messbedingungen insbesondere auf die Partikelaufladung erfolgt. Das Gerät wurde an Anlagen zur Synthese von SiO2 Nanopartikeln der Degussa AG angewandt. Ein Einfluss von Prozessgrößen auf die Partikelgrößenverteilung wurde beobachtet. Die Eignung des Verfahrens für industrielle Syntheseprozesse nanoskaliger Pulver wurde gezeigt.