Tribocharging of granular materials and influence on their flow.

Once granular materials flow, particles charge because of the triboelectric effect. When particles touch each other, charges are exchanged during contact whether they are made of the same material or not. Surprisingly, when different sizes of particles are mixed together, large particles tend to charge positively while small particles charge negatively. If the particles are relatively small (typically smaller than a millimeter), the electrostatic interaction between the particles becomes significant and leads to aggregation or sticking on the surface of the container holding them. Studying those effects is challenging as the mechanisms that govern the triboelectric effect are not fully understood yet. We show that the patch model (or mosaic model) is suitable to reproduce numerically the flow of triboelectrically charged granular materials as the specific charging of bi-disperse granular materials can be retrieved. We investigate the influence of charging on the cohesion of granular materials and highlight the relevant parameters related to the patch model that influence cohesion. Our results shed new light on the mechanisms of the triboelectric effect as well as on how the charging of granular materials influences cohesion using numerical simulations.

Inhalation powder development without carrier: How to engineer ultra-flying microparticles?

Particle engineering technologies have led to the commercialization of new inhaled powders like PulmoSolTM or PulmoSphereTM. Such platforms are produced by spray drying, a well-known process popular for its versatility, thanks to wide-ranging working parameters. Whereas these powders contain a high drug-loading, we have studied a low-dose case, in optimizing the production of powders with two anti-asthmatic drugs, budesonide and formoterol. Using a Design of Experiments approach, 27 powders were produced, with varying excipient mixes (cyclodextrins, raffinose and maltodextrins), solution concentrations, and spray drying parameters in order to maximize deep lung deposition, measured through fine particle fraction (next generation impactor). Based on statistical analysis, two powders made of hydropropyl-ß-cyclodextrin alone or mixed with raffinose and L-leucine were selected. Indeed, the two powders demonstrated very high fine particle fraction (>55%), considerably better than commercially available products. Deep lung deposition has been correlated to very fine particle size and lower microparticles interactions shown by laser diffraction assays at different working pressures, and particle morphometry. Moreover, the two drugs would be predicted to deposit homogeneously into the lung according to impaction studies. Uniform delivery is fundamental to control symptoms of asthma. In this study, we develop carrier-free inhalation powders promoting very efficient lung deposition and demonstrate the high impact of inter-particular interactions intensity on their aerosolization behaviour.

Engineered-inhaled particles: Influence of carbohydrates excipients nature on powder properties and behavior.

Pulmonary drug administration has long been used for local or systemic treatment due to several advantages. Dry powder inhalers emerge as the most promising due to efficiency, ecologic, and drug stability concerns. Coarse lactose-carrier is still the gold standard when inhalation powders are developed. Despite some efforts to produce new types of powders, the lung drug deposition is still poorly controlled, which will ultimately impact therapeutic effectiveness. In this study, we developed "engineered-inhalation powders" using the spray-drying technique. Multiple carbohydrates excipients were binary mixed and combined with two active pharmaceutical ingredients for asthma therapy (budesonide and formoterol). Particle morphology, from spherical to deflated shapes, was characterized by the number and the depth of dimples measured from SEM images. We define a new characteristic deflation ratio ξ as the product between the number of dimples and their depth. Six different powders having opposite morphologies have been selected and we have demonstrated a linear correlation between the fine particle fraction and the deflation ratio of produced powders. Overall, we showed first that the morphology of inhalable powder can be finely tuned by spray-drying technique when excipients varied. Secondly, we developed stable inhalation powders that simultaneously induced high fine particle fractions (>40%) for two drugs due to their deflated surface. The stability has been evaluated for up to 2 months at room temperature.

Loss-in-weight feeding, powder flow and electrostatic evaluation for direct compression hydroxypropyl methylcellulose (HPMC) to support continuous manufacturing.

Minimizing variability in the feeding process is important for continuous manufacturing since materials are fed individually and can impact the final product. This study demonstrates the importance of measuring powder properties and highlights the need to characterize the feeding performance both offline with multiple refills and in the intended configuration for the continuous manufacturing equipment. The standard grade hydroxypropyl methylcellulose (HPMC) had material buildup on the loss-in-weight feeder barrel from triboelectric charging and resulted in more mass flow excursions and failed refills which were not observed with the direct compression grades. The location of the electrostatic buildup changed when the feeder was connected to a hopper instead of feeding offline into a collection bucket. Overall, the direct compression HPMC exhibited better flow which resulted in more accurate loss-in-weight feeding with less excursions from the target mass flow and all refills were completed in the first attempt. The improvements with the direct compression HPMC would be beneficial when running any continuous process (wet granulation, roller compaction, or direct compression) or other processes where loss-in-weight feeding is utilized, such as melt extrusion or twin screw granulation.

Numerical measurement of flow fluctuations to quantify cohesion in granular materials.

The flow of cohesive granular materials in a two-dimensional rotating drum is investigated using discrete element method simulations. Contacts between particles are modeled based on the widely used model of the spring-dashpot and Coulomb's friction law. A simplified model of intermediate range attraction between grains (i.e., cohesion) has been used in order to reproduce the flow of electrostatic or wet granular materials. Granular flow is generated by means of a rotating drum and the effect of the rotation speed, the friction between the grains, and the cohesion are studied. Significantly different flow behaviors are observed when cohesion is added. Plug flow appears in the rotating drum for a wide range of rotation speeds when cohesion becomes sufficiently strong. We propose a measurement of surface flow fluctuations to quantify the strength of cohesion, inspired by the previous observation of plug flow. Then, we make use of the results to include the effect of cohesion into a theoretical flow model. A good agreement is obtained between theory and numerical measurements of the granular bed's dynamic angle of repose, which allows us to propose a method for estimating the microscopic cohesion between grains based on the measurement of surface fluctuations.

How size ratio and segregation affect the packing of binary granular mixtures.

For reaching high packing fractions, grains of various sizes are often mixed together allowing the small grains to fill the voids created by the large ones. However, in most cases, granular segregation occurs leading to lower packing fractions. We performed a wide set of experiments with different binary granular systems, proving that two main parameters are respectively the volume fraction f of small beads and the grain size ratio α. In addition, we show how granular segregation affects the global packing fraction. We propose a model with a strong dependency on α that takes into account possible granular segregation. Our model is in good agreement with both earlier experimental and simulation data.

From jamming to fast compaction dynamics in granular binary mixtures.

Binary granular mixtures are known to show various packing arrangements depending on both fractions and size ratios of their components. While the final packing fraction can be estimated by geometrical arguments, the dynamics of the pile submitted to gentle vibrations towards a dense state is seen to be highly size ratio dependent. We observe experimentally a diverging compaction characteristic time close to a critical size ratio, such that the grain mobility in the packing is the lowest close to the percolation threshold, when small particles can pass through the voids left by the large ones. Moreover, we evidence a fast compaction dynamics regime when the grain size ratio is large enough.

Decompaction of wet granular materials under freeze-thaw cycling.

The packing fraction dynamics of a wet granular material submitted to freeze-thaw cycling is investigated experimentally. The dynamics is strongly influenced by the liquid volume fraction ω in the considered range of 0.03<ω<0.32. This range of liquid contents covers different regimes of wetness from the creation of the capillary network until the formation of large clusters and finally close to the saturated case. For the liquid contents ω≳0.15, the pile experiences a decompaction until a particular value of the packing fraction 0.56 corresponding to a random loose packing configuration for monosized spheres. Moreover, the decompaction starts after a cycling number that decreases exponentially with the liquid content. Finally, we show that the packing dynamics can be well modeled on the basis of a Landau potential with an asymmetric double-well structure. The onset of decompaction represents the tendency of the system to stay in a metastable state. After several cycles, the forces induced by the thermal cycling and local stochastic rearrangements of the grains can drive the system to overcome the energy barrier of the cohesive forces.

Statics and dynamics of magnetocapillary bonds.

When ferromagnetic particles are suspended at an interface under magnetic fields, dipole-dipole interactions compete with capillary attraction. This combination of forces has recently given promising results towards controllable self-assemblies as well as low-Reynolds-number swimming systems. The elementary unit of these assemblies is a pair of particles. Although equilibrium properties of this interaction are well described, the dynamics remain unclear. In this paper, the properties of magnetocapillary bonds are determined by probing them with magnetic perturbations. Two deformation modes are evidenced and discussed. These modes exhibit resonances whose frequencies can be detuned to generate nonreciprocal motion. A model is proposed that can become the basis for elaborate collective behaviors.

Quantitatively mimicking wet colloidal suspensions with dry granular media.

Athermal two-dimensional granular systems are exposed to external mechanical noise leading to Brownian-like motion. Using tunable repulsive interparticle interaction, it is shown that the same microstructure as that observed in colloidal suspensions can be quantitatively recovered at a macroscopic scale. To that end, experiments on granular and colloidal systems made up of magnetized particles as well as computer simulations are performed and compared. Excellent agreement throughout the range of the magnetic coupling parameter is found for the pair distribution as well as the bond-orientational correlation functions. This finding opens new ways to efficiently and very conveniently explore phase transitions, crystallization, nucleation, etc in confined geometries.

Breaking arches with vibrations: the role of defects.

We present experimental and numerical results regarding the stability of arches against external vibrations. Two-dimensional strings of mutually stabilizing grains are geometrically analyzed and subsequently submitted to a periodic forcing at fixed frequency and increasing amplitude. The main factor that determines the granular arch resistance against vibrations is the maximum angle among those formed between any particle of the arch and its two neighbors: the higher the maximum angle is, the easier it is to break the arch. On the basis of an analysis of the forces, a simple explanation is given for this dependence. From this, interesting information can be extracted about the expected magnitudes of normal forces and friction coefficients of the particles composing the arches.

A pendulum test as a tool to evaluate viscous friction parameters in the equine fetlock joint.

An equine fetlock joint pendulum test was studied and the influence of post mortem time and intra-articular lipid solvent on the viscous frictional response examined. Fresh equine digits (group 1, n=6 controls; group 2, n=6 lipid solvent) were mounted on a pendulum tribometer. Assuming that pendular joint damping could be modelled by a harmonic oscillator fluid damping (HOFD), damping time (τ), viscous damping coefficient (c) and friction coefficient (µ) were monitored for 5h under experimental conditions (400N; 20°C). In all experiments, pendular joint damping was found to follow an exponential decay function (R(2)=0.99714), which confirmed that joint damping was fluid. The evolution of τ, c and µ was found to be significantly (P<0.05) different in the two groups, with a decrease in τ and an increase in c and µ that was faster and more prominent in digits from group 2. It was concluded that pendular joint damping could be modelled by a HOFD model. The influence of post mortem time on results suggested that, ideally, joint mechanical properties should only be tested on fresh cadavers at the same post mortem time. Moreover, the addition of lipid solvent was found to be responsible for upper viscous friction parameters and for a reduced damping time, which suggested that articular lubricating ability was compromised. This equine pendulum test could be used to test the efficacy of various bio-lubricant treatments.

Swarming and swirling in self-propelled polar granular rods.

Using experiments with anisotropic vibrated rods and quasi-2D numerical simulations, we show that shape plays an important role in the collective dynamics of self-propelled (SP) particles. We demonstrate that SP rods exhibit local ordering, aggregation at the side walls, and clustering absent in round SP particles. Furthermore, we find that at sufficiently strong excitation SP rods engage in a persistent swirling motion in which the velocity is strongly correlated with particle orientation.