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Abstract Innovative soft robotic grippers, such as granular grippers, enable the automated handling of a wide spectrum of different geometries, increasing the flexibility and robustness of industrial production systems. Granular grippers vary in their design as well as in their configuration, which affects the specific characteristics and capabilities regarding grippable objects. Relevant aspects are the selection of granulates and membranes, as they affect the deformability. This influences the achievable gripping forces, which vary with the gripped objects geometry. On the basis of experimental studies, the modeling of interpolations as well as through experimental validations, the present research investigates the influences of different configurations on the achievable gripping forces for a specific concept of an innovative vacuum-based granular gripper. Specifically, the focus lies on design as well as configuration parameters, which could influence the achievable gripping force. Influencing parameters are determined based on a literature review of similar gripping concepts. Various adjustment possibilities are identified, such as materials of granulates or membranes. The possible configuration options are experimentally analyzed with a one-factor-at-a-time approach. The possibility of modelling the effects of their interrelations on the achievable gripping force is examined with approaches for linear models and compared to interpolations based on Machine Learning. Especially the granulate filling level and the membrane configuration exhibit the largest influences, which were best predicted with the approach based on artificial neural networks. A selection of an optimized gripper configuration for a specified object set as well as possible further developments such as a continuous expandability of the approaches and integrations with simulations are discussed. As a result of these analyses, this research provides methodologies for an optimized selection of a gripper configuration for an improved object-specific achievable gripping force and allows for more efficient handling processes with the examined type of vacuum-based granular gripper.

Future industrial applications of microparticle fractionation with deterministic lateral displacement (DLD) devices are hindered by exceedingly low throughput rates. To enable the necessary high-volume flows, high flow velocities as well as high aspect ratios in DLD devices have to be investigated. However, no experimental studies have yet been conducted on the fractionation of bi-disperse suspensions containing particles below 10 µm with DLD at a Reynolds number (Re) above 60. Furthermore, devices with an aspect ratio of more than 4:1, which require advanced microfabrication, are not known in the DLD literature. Therefore, we developed a suitable process with deep reactive ion etching of silicon and anodic bonding of a glass lid to create pressure-resistant arrays. With a depth of 120 µm and a gap of 23 µm between posts, a high aspect ratio of 6:1 was realized, and devices were investigated using simulations and fractionation experiments. With the two-segmented array of 3° and 7° row shifts, critical diameters of 8 µm and 12 µm were calculated for low Re conditions, but it was already known that vortices behind the posts can shift these values to lower critical diameters. Suspensions with polystyrene particles in different combinations were injected with an overall flow rate of up to 15 mL/min, corresponding to Re values of up to 90. Suspensions containing particle combinations of 2 µm with 10 µm as well as 5 µm with 10 µm were successfully fractionated, even at the highest flow rate. Under these conditions, a slight widening of the displacement position was observed, but there was no further reduction in the critical size as it was for Re = 60. With an unprecedented fractionation throughput of nearly 1 L per hour, entirely new applications are being developed for chemical, pharmaceutical, and recycling technologies.

Since the early 2010s, after decades of premature excitement and disillusionment, the field of artificial intelligence (AI) is experiencing exponential growth, with massive real-world applications and high adoption rates both in daily life and in industry. In particle technology, there are already many examples of successful AI applications, for predictive modeling, process control and optimization, fault recognition, even for mechanistic modeling. However, in comparison to its still untapped potential and to other industries, further expansion in adoption rates and, consequently, gains in productivity, efficiency, and cost reduction are still possible. This review article is intended to introduce AI and its application scenarios and provide an overview and examples of current use cases of different aspects and unit operations in particle technology, such as grinding, extrusion, synthesis, characterization, or scale-up. In addition, hybrid modeling approaches are presented with examples of the intelligent combination of different methods to reduce data requirements and achieve beneficial synergies. Finally, an outlook for future opportunities is given, depicting promising approaches, currently being in the conception or implementation phase.

Understanding of generation, extent and location of thermomechanical stress in small-scale (< 3 g) ram and twin-screw melt-extrusion is crucial for mechanistic correlations to the stability of protein particles (lysozyme and BSA) in PEG-matrices. The aim of the study was to apply and correlate experimental and numerical approaches (1D and 3D) for the evaluation of extrusion process design on protein stability. The simulation of thermomechanical stress during extrusion raised the expectation of protein degradation and protein particle grinding during extrusion, especially when TSE was used. This was confirmed by experimental data on protein stability. Ram extrusion had the lowest impact on protein unfolding temperatures, whereas TSE showed significantly reduced unfolding temperatures, especially in combination with kneading elements containing screws. In TSE, the mechanical stress in the screws always exceeded the shear stress in the die, while mechanical stress within ram extrusion was generated in the die, only. As both extruder designs revealed homogeneously distributed protein particles over the cross section of the extrudates for all protein-loads (20–60%), the dispersive power of TSE revealed not to be decisive. Consequently, the ram extruder would be favored for the production of stable protein-loaded extrudates in small scale.

Despite the variety of solid electrolytes available, no single solid electrolyte has been found that meets all the requirements of the successor technology of lithium-ion batteries in an optimum way. However, composite hybrid electrolytes that combine the desired properties such as high ionic conductivity or stability against lithium are promising. The addition of conductive oxide fillers to sulfide solid electrolytes has been reported to increase ionic conductivity and improve stability relative to the individual electrolytes, but the influence of the mixing process to create composite electrolytes has not been investigated. Here, we investigate Li3PS4 (LPS) and Li7La3Zr2O12 (LLZO) composite electrolytes using electrochemical impedance spectroscopy and distribution of relaxation times. The distinction between sulfide bulk and grain boundary polarization processes is possible with the methods used at temperatures below 10 °C. We propose lithium transport through the space-charge layer within the sulfide electrolyte, which increases the conductivity. With increasing mixing intensities in a high-energy ball mill, we show an overlay of the enhanced lithium-ion transport with the structural change of the sulfide matrix component, which increases the ionic conductivity of LPS from 4.1 × 10−5 S cm−1 to 1.7 × 10−4 S cm−1.

In biotechnological processes, filamentous microorganisms are known for their broad product spectrum and complex cellular morphology. Product formation and cellular morphology are often closely linked, requiring a well-defined level of mechanical stress to achieve high product concentrations. Macroparticles were added to shake flask cultures of the filamentous actinomycete Lentzea aerocolonigenes to find these optimal cultivation conditions. However, there is currently no model concept for the dependence of the strength and frequency of the bead-induced stress on the process parameters. Therefore, shake flask simulations were performed for combinations of bead size, bead concentration, bead density and shaking frequency. Contact analysis showed that the highest shear stresses were caused by bead-bottom contacts. Based on this, a newly generated characteristic parameter, the stress area ratio (SAR), was defined, which relates the bead wall shear and normal stresses to the total shear area. Comparison of the SAR with previous cultivation results revealed an optimum pattern for product concentration and mean product-to-biomass related yield coefficient. Thus, this model is a suitable tool for future optimization, comparison and scaling up of shear-sensitive microorganism cultivation. Finally, the simulation results were validated using high-speed recordings of the bead motion on the bottom of the shake flask.

Abstract Filamentous microorganisms are used as molecular factories in industrial biotechnology. In 2007, a new approach to improve productivity in submerged cultivation was introduced: microparticle‐enhanced cultivation (MPEC). Since then, numerous studies have investigated the influence of microparticles on the cultivation. Most studies considered MPEC a morphology engineering approach, in which altered morphology results in increased productivity. But sometimes similar morphological changes lead to decreased productivity, suggesting that this hypothesis is not a sufficient explanation for the effects of microparticles. Effects of surface chemistry on particles were paid little attention, as particles were often considered chemically‐inert and bioinert. However, metal oxide particles strongly interact with their environment. This review links morphological, physical, and chemical properties of microparticles with effects on culture broth, filamentous morphology, and molecular biology. More precisely, surface chemistry effects of metal oxide particles lead to ion leaching, adsorption of enzymes, and generation of reactive oxygen species. Therefore, microparticles interfere with gene regulation, metabolism, and activity of enzymes. To enhance the understanding of microparticle‐based morphology engineering, further interactions between particles and cells are elaborated. The presented description of phenomena occurring in MPEC eases the targeted choice of microparticles, and thus, contributes to improving the productivity of microbial cultivation technology.

Current research focuses on lithium-ion battery cells with a high energy density and efficient fast-charging capabilities. However, transport limitations, and, therefore, the uniform diffusion of lithium-ions across the electrode layers, remain a challenge and could lead to reduced cell performance. One approach to overcome these transport challenges is the use of subsequently produced two-layer anodes with the particle size variation of spherical graphite (x50 = 18 µm; x50 = 11 µm). Thereby, a defined pore network is created, which reduces the ionic resistance and ensuring improved fast charging capabilities. The analysis focuses on the evaluation of electrode properties and the electrochemical performance. By examining the pore size distribution of the anodes, it has been found that during the manufacturing of the two-layer anodes, carbon black and binder particles are transported into the existing microstructure of the lower layer, resulting in localized densification between the anode layers. This could also be supported by color measurements. This effect also extends to electrochemical investigations, with electrochemical impedance spectroscopy showing significantly lower ionic resistances in all two-layer anodes. Reduced ionic resistance and tortuosity near the separator due to absorption effects enhance the ion diffusion and have a direct impact on anode performance. Cell ageing analysis showed a significant capacity decrease of almost 15 mAh g −1 in the single-layer references only, in contrast to the stability of the two-layer anodes. This could also be attributed to the reduced ionic resistance and active counteraction of binder migration. In conclusion, this study highlights how subsequently produced two-layer anodes significantly shape the electrode properties and cell performance of lithium-ion batteries.

As manufacturing and assembly processes continue to require more adaptable systems for automated handling, innovative solutions for universal gripping are emerging. These grasping systems can enable the handling of wide varieties of shapes, with gripping forces varying with grasped geometries. For the efficient usage of handling systems, precise offline and online prediction models for resulting grasping forces for different objects are necessary. In previous research, a flexible vacuum-based granular gripper was developed, for which no option for predicting gripping forces is currently available. Various gripping force prediction methodologies within the current state of the art are examined and evaluated. For an assessment of grasping forces of previously untested objects for the examined gripper with limited data and low computational effort, two methodologies are proposed. An analytical, 2D-geometry-derived gripper-specific metric for geometries is compared to a methodology based on similarities of objects to a small existing dataset. The applicability and prediction quality for different object types is analyzed through validation experiments. Gripping force estimations are possible with both methodologies, with individual weaknesses towards geometric features such as air permeabilities. With further development, robust predictions of gripping forces could be achieved for a wide range of unknown object geometries with limited experimental effort.

A novel water-based lithium ferro-phosphate (LFP) cathode manufacturing process characterized by a significant reduction in the amount of solvent has been developed (semi-dry). To establish and validate this new process, Polytetrafluorethylene (PTFE) is used as a binder, with a binder content of 1 wt.%, minimizing the amount of inactive material within the electrode. Extrusion screws with multiple kneading zones stress the PTFE more intensively and thus produce more and smaller fibrils. The resulting extent of fibrillation is quantified by melting enthalpy as well as mechanical electrode properties. The degree of fibrillation of the binder in an electrode is known to influence the conductive electric and ionic pathways, which in turn affect the discharge capacity. It is shown that this process provides a flexible cathode layer that achieves a specific capacitance of 155 mAh g−1 in initial cycling tests at 0.1 C. Compared to a conventionally processed LFP cathode, the discharge capacity and overall energy output are significantly increased, and the overall energy consumption decreases for the semi-dry processed LFP cathodes.

Lentzeaaerocolonigenes, as an actinomycete, is a natural producer of the antibiotic and antitumoral drug rebeccamycin. Due to the filamentous cellular morphology handling in cultivations is challenging; therefore, morphology engineering techniques are mandatory to enhance productivity. One promising approach described in the literature is the addition of mineral particles in the micrometer range to precisely adjust cellular morphology and the corresponding product synthesis (microparticle-enhanced cultivation, MPEC). Glass microparticles are introduced in this study as a novel supplementation type for bioprocess intensification in filamentous organisms. Several investigations were conducted to screen for an optimal particle setup, including particle size and concentration regarding their impact and effects on enhanced productivity, microparticle incorporation behavior into the biopellets, the viability of pellets, and morphological changes. Glass microparticles (10 g·L−1) with a median diameter of 7.9 µm, for instance, induced an up to fourfold increase in product synthesis accompanied by overall enhanced viability of biomass. Furthermore, structural elucidations showed that biopellets isolated from MPEC tend to have lower hyphal density than unsupplemented control pellets. In this context, oxygen microprofiling was conducted to better understand how internal structural changes interwind with oxygen supply into the pellets. Here, the resulting oxygen profiles are of a contradictive trend of steeper oxygen consumption with increasing glass microparticle supplementation. Eventually, MPEC was combined with another promising cultivation strategy, the supplementation of soy lecithin (7.5 g·L−1), to further increase the cultivation performance. A combination of both techniques in an optimized setup resulted in a rebeccamycin concentration of 213 mg·L−1 after 10 days of cultivation, the highest value published so far for microparticle-supplemented shake flask cultivations of L. aerocolonigenes.

Progress in new sustainable technologies depends on the development of battery materials, specifically on safer, low-cost, and higher energy density batteries. One new type of materials are the halide solid electrolytes (HSEs), which have been shown to exhibit high ionic conductivity, deformability, and oxidative stability. Here, the synthesis of Li3InCl6 (LIC) HSEs by ball-milling followed by dry room annealing is investigated. Crystal structure, particle size, and ionic conductivity are analyzed using a combination of X-ray diffraction, transmission electron microscopy, and electrochemical impedance spectroscopy. Dry room annealing increases the presence of impurities in the sample but also increases the Li+ ionic conductivity up to 1.03 mS cm−1. Additional pulsed-field gradient and relaxation time NMR measurements were performed to understand the lithium diffusion in the LIC samples. Two-dimensional diffusion – T2 relaxation correlation and T2 relaxation exchange measurements showed that there are multiple unique Li atomic motion sites, which are correlated to different rates of diffusive, micrometer-scale motion. This work outlines a simple solid-state synthesis approach and a novel strategy for designing advanced materials, understanding the ionic conduction, as well as the challenges in scalable wet processing of halide-based cathode sheets for solid-state battery applications.

Lithium-ion batteries (LIBs) provide the largest source of electrical energy storage today. This paper covers the use of comminution processes and, thus, crushers and mills for particle breakage and dispersing, as well as classifiers for particle separation within the process chain, from the raw material to the final lithium battery cell and its recycling at end of life. First of all, the raw materials for the active material production have to be produced either by processing primary raw materials, or by recycling the spent lithium batteries. The end-of-life battery cells have to be shredded, the materials separated and then milled in order to achieve the so-called black mass, which provides a secondary material source with very valuable components. Using these materials for the synthesis of the cathode active materials, milling has to be applied in different stages. The natural graphite, increasingly used as anode material, has to be designed in mills and classifiers for achieving targeted properties. Nanosized silicon is produced by nanomilling using stirred media mills as a primary option. Conductive additives for LIBs, like carbon black, have to be dispersed in a solvent with machines like planetary mixers, extruders or stirred media mills. In the future, mechanochemical synthesis of solid electrolytes will especially require additional application of comminution processes.

In the drying process of electrodes for lithium-ion batteries, the layer structure is defined and can only be influenced slightly in the subsequent process steps. An essential point in the drying process is the fixation of the binder, ensuring both the adhesive and cohesive strength of the electrode. It is known that high drying rates lead to the segregation of the binder in the direction of the coating surface, which results in reduced mechanical stability of the electrode. In a previous publication, an experimental approach was used to investigate the underlying processes that influence binder migration. These results are now used in a model-based approach to describe the binder migration using the convection–diffusion equation. The convective term originates from the shrinkage behavior of the layer during drying due to the relative movement between the active material particles and the solvent in which the binder is dissolved or dispersed; it is expected to be the cause of the binder migration. The diffusive term, representing the binder movement in the solvent, counteracts segregation. The interaction of these forces is simulated at different drying temperatures and the associated drying rates.

To gain better understanding of the safety behavior of lithium-ion batteries under mechanical stress, crush tests are performed and reported in literature and in standards. However, many of these tests are conducted without the use of a cell clamping device, whereas external pressure is applied to the cell in a battery module in applications such as in an electric vehicle. The objective of this manuscript is to determine the effect of differing external compression on the thermal runaway of battery cells. Therefore, in this study, crush tests are performed with a hemispherical punch in a battery cell test chamber on commercially available 5 Ah pouch cells in a clamping device at four different normal stresses. The results are compared to cells that are free to expand with gas evolution. It is shown that applying compression to the cells not only results in a greater reproducibility of the experiments but that it also affects the thermal runaway process itself. With decreasing clamping stresses, the reaction time of the thermal runaway is increased by up to 19%, and the mass ejection is decreased by up to 10%, which, in turn, strongly influences the measurable gas concentrations by up to 80%. Based on this, a defined clamping compression was selected to obtain comparable results for different cell formats.

Silicon (Si) is considered a promising anode active material to enhance energy density of lithium-ion batteries. Many studies have focused on new structures and the electrochemical performance, but only a few investigated the particulate properties in detail. Therefore, a comprehensive study on the impact of Si content (5, 10, 15 wt.%) and particle size (120, 160, 250 nm) of core–shell structured Si@Gr composites on particulate and electrode properties was conducted. It was shown that both parameters had significant impact on the specific surface area (SSA) of particles, which was later correlated to the initial capacities and coulombic efficiencies (ICEs). Furthermore, changes in pore size distribution and electrical conductivity were found. The built full cells showed high initial capacities (>150 mAh g−1), good rate capability (75% at 1 C, 50% at 2 C) and ICEs (>80%). The energy density was found to increase by 32% at 15 wt.% Si compared to graphite (Gr), indicating the future potential of Si. In addition, the impact of a carbon coating was investigated (Si@Gr/C), which led to a reduction in SSA, improved particle stability and higher capacity retention. Consequently, this study emphasizes the importance of also investigating the particulate properties of Si anodes.

Despite numerous research on new active materials for anodes, graphite remains the most commonly used material in Li-ion batteries. The spherical shape of the graphite particles has proven to be beneficial for application in electric vehicles, especially for fast charging. So far, the spheroidization of natural flake graphite is conducted by a rigid and inefficient cascade process. In this work, a scalable classifier system was used for spheroidization, and it was demonstrated that a spheroidization time of 15 min is sufficient to improve material properties and enhance electrochemical performance while maintaining high process yields of 55%. Insights into the influence of the morphology on the intrinsic and structural properties of the graphite particles and manufactured electrodes are provided. Spheroidization creates a more efficient pore network in the coating layer while reducing the internal resistance and increasing the surface area of the particles by a factor of 1.8. We demonstrate that the spherical shape improves the discharge rate capability by 1.8, and the specific charge capacity could be enhanced by more than 237% at a C-rate of 3. An additional carbon coating could significantly decrease the specific surface area and increase the specific capacity at high C-rates.

The administration of living microorganisms is of special interest, with regard to probiotic microorganisms providing health benefits to the patient. Effective dosage forms require the preservation of microbial viability until administration. Storage stability can be improved by drying, and the tablet is an especially attractive final solid dosage form due to its ease of administration and its good patient compliance. In this study, drying of the yeast Saccharomyces cerevisiae via fluidized bed spray granulation is investigated, as the probiotic Saccharomyces boulardii is a variety of it. Fluidized bed granulation enables faster drying than lyophilization on the one hand and lower temperatures than spray drying on the other hand, which are the two predominantly used techniques for life-sustaining drying of microorganisms. Yeast cell suspensions enriched with protective additives were sprayed onto the carrier particles of common tableting excipients, namely, dicalcium phosphate (DCP), lactose (LAC) and microcrystalline cellulose (MCC). Different protectants, such as mono-, di-, oligo- and polysaccharides, but also skimmed milk powder and one alditol, were tested; as they themselves, or chemically similar molecules, are known from other drying technologies to stabilize biological structures such as cell membranes, and thus, improve survival during dehydration. With the combined use of trehalose and skimmed milk powder, survival rates were 300 times higher than without the use of protective additives. In addition to these formulation aspects, the influence of process parameters such as inlet temperature and spray rate were considered. The granulated products were characterized regarding their particle size distribution, moisture content and the viability of the yeast cells. It has been shown that thermal stress on the microorganisms is especially critical, which can be reduced, for example, by reducing the inlet temperature or increasing the spray rate; however, formulation parameters such as cell concentration also influenced survival. The results were used to specify the influencing factors on the survival of microorganisms during fluidized bed granulation and to derive their linkages. Granules based on the three different carrier materials were tableted and the survival of the microorganisms was evaluated and linked to the tablet tensile strength achieved. Using LAC enabled the highest survival of the microorganisms throughout the considered process chain.

The purpose of this study was to investigate the deformation behavior of non-spherical particles during high-load compaction using the multi-contact discrete element method (MC-DEM). To account for non-spherical particles, the bonded multi-sphere method (BMS), which incorporates intragranular bonds between particles, and the conventional multi-sphere (CMS), where overlaps between particles are allowed to form a rigid body, were used. Several test cases were performed to justify the conclusions of this study. The bonded multi-sphere method was first employed to study the compression of a single rubber sphere. This method’s ability to naturally handle large elastic deformations is demonstrated by its agreement with experimental data. This result was validated further through detailed finite element simulations (multiple particle finite element method (MPFEM)). Furthermore, the conventional multi-sphere (CMS) approach, in which overlaps between particles are allowed to form a rigid body, was used for the same objective, and revealed the limitations of this method in successfully capturing the compression behavior of a single rubber sphere. Finally, the uniaxial compaction of a microcrystalline cellulose-grade material, Avicel® PH 200 (FMC BioPolymer, Philadelphia, PA, USA), subjected to high confining conditions was studied using the BMS method. A series of simulation results was obtained with realistic non-spherical particles and compared with the experimental data. For a system composed of non-spherical particles, the multi-contact DEM showed very good agreement with experimental data.

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In order to reduce the cost of lithium-ion batteries, production scrap has to be minimized. The reliable detection of electrode defects allows for a quality control and fast operator reaction in ideal closed control loops and a well-founded decision regarding whether a piece of electrode is scrap. A widely used inline system for defect detection is an optical detection system based on line scan cameras and specialized lighting. The cameras scan the electrode, and brightness differences on the surface are detected and processed inline. The characteristics of the defect image are used for automated classification of the defects based on image features. Furthermore, the detailed detection of defects allows for the identification of causes. This paper describes the working principle of such an inline detection system, the catalog of typical defects, and the image features used to classify them automatically. Furthermore, we propose and discuss causes and effects of the different defect types on the basis of the literature and expert experience. In combination with tracking and tracing, this enables the manufacturer to reduce scrap by detecting defects early in the production chain.

The functional behaviour of tablets is strongly influenced by their manufacturing process and the choice of excipients. Water uptake and swelling are prerequisites for tablet disintegration, dispersion and hence active pharmaceutical ingredient (API) dissolution. High proportions of polymeric excipients in tablets, which are typically used as API carriers in amorphous solid dispersions (ASDs), may be challenging due to the formation of a gelling polymer network (GPN). In this study, systematic investigations into the formulation development of tablets containing polymeric and other excipients are performed by water uptake and swelling analysis. The impact of tablet composition and porosity as well as pH of the test medium are investigated. The pH affects the analysis results for Eudragit L100–55 and Eudragit EPO. HPMC and Kollidon VA64 inhibit water uptake and swelling of tablets due to the formation of a GPN. High tablet porosity, coarse particle size of the polymer and the addition of fillers and disintegrants can reduce the negative impact of a GPN on tablet performance. The application of lubricants slows down the analysed processes. Water uptake and swelling data are fitted to an empirical model obtaining four characteristic parameters to facilitate the simple quantitative assessment of varying tablet formulations and structural properties.

Within this study, tablets microstructure was investigated by X-ray microtomgraphy. The aim was to gain information about their microstructure, and thus, derive deeper interpretation of tablet properties (mechanical strength, component distribution) and qualified property functions. Challenges in image processing are discussed for the correct identification of solids and voids. Furthermore, XMT measurements are critically compared with complementary physical methods for characterizing active pharmaceutical ingredient (API) content and porosity and its distribution (mercury porosimetry, calculated tablet porosity, Focused Ion Beam-Scanning Electron Microscopy (FIB-SEM)). The derived porosity by XMT is generally lower than the calculated porosity based on geometrical data due to the resolution of the XMT in relation to the pore sizes in tablets. With rising compactions stress and API concentration, deviations between the actual and the calculated API decrease. XMT showed that API clusters are present for all tablets containing >1 wt% of ibuprofen. The 3D orientation of the components is assessable by deriving cord lengths along all dimensions of the tablets. An increasing compaction stress leads to rising cord lengths, showing higher connectivity of the respective material. Its lesser extent in the z-direction illustrates the anisotropy of the compaction process. Additionally, cracks in the fabric are identified in tablets without visible macroscopic damage. Finally, the application of XMT provides valuable structural insights if its limitations are taken into account and its strengths are fostered by advanced pre- and post-processing.

In order to develop competitive all-solid-state batteries, cost efficient and highly scalable manufacturing methods need to be identified and evaluated. In this work, the scalable production of a polymer solid electrolyte (SPE) separator was investigated to gain deep knowledge on how the process parameters influences product quality and reproducibility. In detail, a sustainable, solvent-free manufacturing route for the fabrication of SPE films based on a PEO based block copolymer through a novel, highly scalable film casting process was developed. The scalability, energy consumption and the SPE separator properties film thickness, density, ionic conductivity, polymer degradation and lithium salt distribution were evaluated in comparison to a reference calendering process. Compared to the considered reference process, the developed film casting process showed improved precision at higher throughputs regarding a constant film thickness below 30 μm and SPE density. The novel film casting process showed a significantly lowered energy consumption, which is of major importance with respect to production costs and sustainability. At the same time, the electrochemical performance was preserved with an ionic conductivity of approx. 0.2 mS cm−1 at 80 °C as well as a rate capability of approx. 60 mAh gLFP−1 at 1C discharge rate.

The return to the Moon is an important short-term goal of NASA and other international space agencies. To minimize mission risks, technologies, such as rovers or regolith processing systems, must be developed and tested on Earth using lunar regolith simulants that closely resemble the properties of real lunar soil. So far, no singular lunar simulant can cover the multitude of use cases that lunar regolith involves, and most available materials are poorly characterized. To overcome this major gap, a unique modular system for flexible adaptable novel lunar regolith simulants was developed and chemically characterized in earlier works. To supplement this, the present study provides comprehensive investigations regarding geotechnical properties of the three base regolith simulant systems: TUBS-M, TUBS-T, and TUBS-I. To evaluate the engineering and flow properties of these heterogeneous materials under various conditions, shear tests, particle size analyses, scanning electron microscope observations, and density investigations were conducted. It was shown that small grains x50 = 76.7 to 96.0 µm). Further, ring shear and densification tests revealed correlations with damage mechanisms caused by local stress peaks for grains in the mm range. In addition, an explanation for the occurrence of considerable differences in the literature-based data for particle sizes was established by comparing various measurement procedures. The present study shows detailed geotechnical investigations of novel lunar regolith simulants, which can be used for the development of equipment for future lunar exploration missions and in situ resource utilization under realistic conditions. The results also provide evidence about possible correlations and causes of known soil-induced mission risks that so far have mostly been described phenomenologically.

Due to the ever-growing importance of rechargeable lithium-ion batteries, the development of electrode materials and their processing techniques remains a hot topic in academia and industry. Even the well-developed and widely utilized active materials present issues, such as surface reactivity, irreversible capacity in the first cycle, and ageing. Thus, there have been many efforts to modify the surface of active materials to enhance the electrochemical performance of the resulting electrodes and cells. Herein, we review the attempts to use polymer coatings on the anode active materials. This type of coating stands out because of the possibility of acting as an artificial solid electrolyte interphase (SEI), serving as an anode protective layer. We discuss the prominent examples of anodes with different mechanisms: intercalation (graphite and titanium oxides), alloy (silicon, tin, and germanium), and conversion (transition metal oxides) anodes. Finally, we give our perspective on the future developments in this field.

The production of nanosuspensions of poorly soluble active pharmaceutical ingredients (API) is a popular technique to counteract challenges regarding bioavailability of such active substances. A subsequent drying of the nanosuspensions is advantageous to improve the long-term stability and the further processing into solid oral dosage forms. However, associated drying operations are critical, especially with regard to nanoparticle growth, loss in redispersibility and associated compromised bioavailability. This work extends a previous study regarding the applicability of an API (itraconazole) nanosuspension as a granulation liquid in a fluidized bed process with focus on the influence of applied formulation parameters on the structure of obtained nanoparticle-loaded granules and their nanoparticle redispersibility. Generally, a higher dissolution rate of the carrier material (glass beads, lactose, mannitol or sucrose) and a higher content of a matrix former/hydrophilic polymer (PVP/VA or HPMC) in the granulation liquid resulted in the formation of coarser and more porous granules with improved nanoparticle redispersibility. HPMC was found to have advantages as a polymer compared with PVP/VA. In general, a better redispersibility of the nanoparticles from the granules could be associated with better dispersion of the API nanoparticles at the surface of the granules as deduced from the thickness of nanoparticle-loaded layers around the granules. The layer thickness on granules was assessed by means of confocal Raman microscopy. Finally, the dispersion of the nanoparticles in the granule layers was exemplarily described by calculation of theoretical mean nanoparticle distances in the granule layers and was correlated with data obtained from redispersibility studies.

In recent years, the field of Artificial Intelligence (AI) is experiencing a boom, caused by recent breakthroughs in computing power, AI techniques, and software architectures. Among the many fields being impacted by this paradigm shift, process engineering has experienced the benefits caused by AI. However, the published methods and applications in process engineering are diverse, and there is still much unexploited potential. Herein, the goal of providing a systematic overview of the current state of AI and its applications in process engineering is discussed. Current applications are described and classified according to a broader systematic. Current techniques, types of AI as well as pre‐ and postprocessing will be examined similarly and assigned to the previously discussed applications. Given the importance of mechanistic models in process engineering as opposed to the pure black box nature of most of AI, reverse engineering strategies as well as hybrid modeling will be highlighted. Furthermore, a holistic strategy will be formulated for the application of the current state of AI in process engineering.

The electrification of the air transport sector demands for an energy storage that adds as little volume and weight to the overall system as possible. Regarding this so-called structural battery, composites enable the storage of electrical energy in commonly used load bearing fibre composite structures. A structural battery composite can store electrical energy while bearing mechanical loads, thus reducing parasitic mass and volume. In this study, structural cathodes were prepared by slurry coating carbon fibres with lithium iron phosphate (LFP), polyethylene oxide (PEO), lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) and carbon black. For the structural anodes, the carbon fibres were utilised as active material and slurry coated with PEO and LiTFSI. These structural electrodes as well as a structural separator were characterised by electrochemical cycling. With 139 mAhgAM−1, the structural cathodes demonstrated good utilisation of the active material. The carbon fibres used in the anode exhibited capacities of up to 92 mAhgAM−1. High irreversible lithium losses were observed, which are attributed to the poor electrolyte wetting behaviour of the carbon fibres. A structural battery demonstrator with a lithium metal anode was realised and reached a maximum specific energy of 64 Whkg−1 with respect to electrode and separator weight.

The process chain of electrode production includes calendering as a crucial process step to enhance the volumetric energy density as well as to influence the particle-pore-structure and simultaneously the mechanical and electrochemical properties of the electrode coating. A further way to improve the volumetric energy density is the usage of other materials with higher specific capacity, such as silicon instead of graphite as the active material for anodes. In this study, both opportunities, calendering and using silicon-containing composites, are combined to investigate the relations between material, process and performance. The applied line loads for the compaction are correlated with the silicon mass fraction and lead to a silicon-dependent mathematical model to estimate further line loads for silicon-graphite-composite electrodes. On the basis of established analyzing methods for adhesion strength and deformation behavior, it is shown that with increasing silicon content, the elastic deformation of the electrode coating rises. In addition, the overall porosity of the electrodes is less affected by silicon than the pore size distribution compared to graphite electrodes. Furthermore, the electrical conductivity decreases at higher silicon contents independent of coating density. Moreover, the long-term electrochemical stability deteriorates with increasing silicon content and coating density.

Growing numbers of electric vehicles (EVs) as well as controversial discussions on cost, scarcity and the environmental and social sustainability of primary raw materials that are needed for battery production together emphasize the necessity for battery recycling in the future. Nonetheless, the market for battery recycling is not fully understood and captured in data today. The underlying reasons are found in both market size and various parameters such as the battery-technology mix, the resulting material demand and expected battery lifetime. In consequence, the question of when secondary-material availability from battery recycling is sufficient to satisfy the global cobalt demand for EV applications has not yet been clarified. To address this question, this study estimates the global battery raw-material demand together with the expected amount of the recycled materials by 2035, taking into account a number of parameters affecting future battery material flows. While focusing on cobalt, nickel, lithium, and manganese, the results indicate that the global cobalt demand can be satisfied from secondary sources by the early 2030s in three out of four different technology forecast scenarios. Furthermore, a sensitivity analysis highlights the amount of waste occurring during battery production and battery lifetime as the main drivers for secondary-material availability by 2035.

Cell morphology of filamentous microorganisms is highly interesting during cultivations as it is often linked to productivity and can be influenced by process conditions. Hence, the characterization of cell morphology is of major importance to improve the understanding of industrial processes with filamentous microorganisms. For this purpose, reliable and robust methods are necessary. In this study, pellet morphology and physiology of the rebeccamycin producing filamentous actinomycete Lentzea aerocolonigenes were investigated by microscopy and flow cytometry. Both methods were compared regarding their applicability. To achieve different morphologies, a cultivation with glass bead addition (Ø = 969 μm, 100 g L-1) was compared to an unsupplemented cultivation. This led to two different macro-morphologies. Furthermore, glass bead addition increased rebeccamycin titers after 10 days of cultivation (95 mg L-1 with glass beads, 38 mg L-1 without glass beads). Macro-morphology and viability were investigated through microscopy and flow cytometry. For viability assessment fluorescent staining was used additionally. Smaller, more regular pellets were found for glass bead addition. Pellet diameters resulting from microscopy followed by image analysis were 172 μm without and 106 μm with glass beads, diameters from flow cytometry were 170 and 100 μm, respectively. These results show excellent agreement of both methods, each considering several thousand pellets. Furthermore, the pellet viability obtained from both methods suggested an enhanced metabolic activity in glass bead treated pellets during the exponential production phase. However, total viability values differ for flow cytometry (0.32 without and 0.41 with glass beads) and confocal laser scanning microscopy of single stained pellet slices (life ratio in production phase of 0.10 without and 0.22 with glass beads), which is probably caused by the different numbers of investigated pellets. In confocal laser scanning microscopy only one pellet per sample could be investigated while flow cytometry considered at least 50 pellets per sample, resulting in an increased statistical reliability.

Disintegration and dispersion are functional properties of tablets relevant for the desired API release. The standard disintegration test (SDT) described in different pharmacopoeias provides only limited information on these complex processes. It is considered not to be comparable to the biorelevant conditions due to the frequent occurrence of high hydrodynamic forces, among other reasons. In this study, 3D tomographic laser-induced fluorescence imaging (3D Tomo-LIF) is applied to analyse tablet disintegration and dispersion. Disintegration time (DT) and time-resolved particle size distribution in close proximity to the tablet are determined in a continuously operated flow channel, adjustable to very low fluid velocities. A case study on tablets of different porosity, which are composed of pharmaceutical polymers labelled with a fluorescent dye, a filler, and disintegrants, is presented to demonstrate the functionality and precision of the novel method. DT results from 3D Tomo-LIF are compared with results from the SDT, confirming the analytical limitations of the pharmacopoeial disintegration test. Results from the 3D Tomo-LIF method proved a strong impact of fluid velocity on disintegration and dispersion. Generally, shorter DTs were determined when cross-linked sodium carboxymethly cellulose (NaCMCXL) was used as disintegrant compared to polyvinyl polypyrrolidone (PVPP). Tablets containing Kollidon VA64 were found to disintegrate by surface erosion. The novel method provides an in-depth understanding of the functional behaviour of the tablet material, composition and structural properties under in vivo-like hydrodynamic forces regarding disintegration and the temporal progress of dispersion. We consider the 3D Tomo-LIF in vitro method to be of improved biorelevance in terms of hydrodynamic conditions in the human stomach.

The purpose of this work is to simulate the powder compaction of pharmaceutical materials at the microscopic scale in order to better understand the interplay of mechanical forces between particles, and to predict their compression profiles by controlling the microstructure. For this task, the new framework of multi-contact discrete element method (MC-DEM) was applied. In contrast to the conventional discrete element method (DEM), MC-DEM interactions between multiple contacts on the same particle are now explicitly taken into account. A new adhesive elastic-plastic multi-contact model invoking neighboring contact interaction was introduced and implemented. The uniaxial compaction of two microcrystalline cellulose grades (Avicel® PH 200 (FMC BioPolymer, Philadelphia, PA, USA) and Pharmacel® 102 (DFE Pharma, Nörten-Hardenberg, Germany) subjected to high confining conditions was studied. The objectives of these simulations were: (1) to investigate the micromechanical behavior; (2) to predict the macroscopic behavior; and (3) to develop a methodology for the calibration of the model parameters needed for the MC-DEM simulations. A two-stage calibration strategy was followed: first, the model parameters were directly measured at the micro-scale (particle level) and second, a meso-scale calibration was established between MC-DEM parameters and compression profiles of the pharmaceutical powders. The new MC-DEM framework could capture the main compressibility characteristics of pharmaceutical materials and could successfully provide predictions on compression profiles at high relative densities.

In recent years, the application field of laser powder bed fusion of metals and polymers extends through an increasing variability of powder compositions in the market. New powder formulations such as nanoparticle (NP) additivated powder feedstocks are available today. Interestingly, they behave differently along with the entire laser powder bed fusion (PBF-LB) process chain, from flowability over absorbance and microstructure formation to processability and final part properties. Recent studies show that supporting NPs on metal and polymer powder feedstocks enhances processability, avoids crack formation, refines grain size, increases functionality, and improves as-built part properties. Although several inter-laboratory studies (ILSs) on metal and polymer PBF-LB exist, they mainly focus on mechanical properties and primarily ignore nano-additivated feedstocks or standardized assessment of powder feedstock properties. However, those studies must obtain reliable data to validate each property metric’s repeatability and reproducibility limits related to the PBF-LB process chain. We herein propose the design of a large-scale ILS to quantify the effect of nanoparticle additivation on powder characteristics, process behavior, microstructure, and part properties in PBF-LB. Besides the work and sample flow to organize the ILS, the test methods to measure the NP-additivated metal and polymer powder feedstock properties and resulting part properties are defined. A research data management (RDM) plan is designed to extract scientific results from the vast amount of material, process, and part data. The RDM focuses not only on the repeatability and reproducibility of a metric but also on the FAIR principle to include findable, accessible, interoperable, and reusable data/meta-data in additive manufacturing. The proposed ILS design gives access to principal component analysis (PCA) to compute the correlations between the material–process–microstructure–part properties.

Research and development in the field of metal-based additive manufacturing are advancing steadily every year. In order to increase the efficiency of powder bed fusion of metals using a laser beam system (PBF LB/M), machine manufacturers have implemented extensive optimizations with regard to the laser systems and build volumes. However, the optimization of metallic powder materials using nanoparticle additives enables an additional improvement of the laser–material interaction. In this work, tool steel 1.2709 powder was coated with silicon carbide (SiC), few-layer graphene (FLG), and iron oxide black (IOB) on a nanometer scale. Subsequently, the feedstock material and the modified powder materials were analyzed concerning the reflectance of the laser radiation and processed by PBF-LB/M in a systematic and consistent procedure to evaluate the impact of the nano-additivation on the process efficiency and mechanical properties. As a result, an increased build rate is achieved, exhibiting a relative density of 99.9% for FLG/1.2709 due to a decreased reflectance of this modified powder material. Furthermore, FLG/1.2709 provides hardness values after precipitation hardening with only aging comparable to the original 1.2709 material and is higher than the SiC- and IOB-coated material. Additionally, the IOB coating tends to promote oxide-formation and lack-of-fusion defects.

In pharmaceutical manufacturing, the utmost aim is reliably producing high quality products. Simulation approaches allow virtual experiments of processes in the planning phase and the implementation of digital twins in operation. The industrial processing of active pharmaceutical ingredients (APIs) into tablets requires the combination of discrete and continuous sub-processes with complex interdependencies regarding the material structures and characteristics. The API and excipients are mixed, granulated if required, and subsequently tableted. Thereby, the structure as well as the properties of the intermediate and final product are influenced by the raw materials, the parametrized processes and environmental conditions, which are subject to certain fluctuations. In this study, for the first time, an agent-based simulation model is presented, which enables the prediction, tracking, and tracing of resulting structures and properties of the intermediates of an industrial tableting process. Therefore, the methodology for the identification and development of product and process agents in an agent-based simulation is shown. Implemented physical models describe the impact of process parameters on material structures. The tablet production with a pilot scale rotary press is experimentally characterized to provide calibration and validation data. Finally, the simulation results, predicting the final structures, are compared to the experimental data.

In this paper, a widely mechanistic model was developed to depict the rheological behaviour of nanoparticulate suspensions with solids contents up to 20 wt.%, based on the increase in shear stress caused by surface interaction forces among particles. The rheological behaviour is connected to drag forces arising from an altered particle movement with respect to the surrounding fluid. In order to represent this relationship and to model the viscosity, a hybrid modelling approach was followed, in which mechanistic relationships were paired with heuristic expressions. A genetic algorithm was utilized during model development, by enabling the algorithm to choose among several hard-to-assess model options. By the combination of the newly developed model with existing models for the various physical phenomena affecting viscosity, it can be applied to model the viscosity over a broad range of solids contents, shear rates, temperatures and particle sizes. Due to its mechanistic nature, the model even allows an extrapolation beyond the limits of the data points used for calibration, allowing a prediction of the viscosity in this area. Only two parameters are required for this purpose. Experimental data of an epoxy resin filled with boehmite nanoparticles were used for calibration and comparison with modelled values.

The bulk properties of powders depend on material characteristics and size of the primary particles. During storage and transportation processes in the powder processing industry, the material undergoes various modes of deformation and stress conditions, e.g., due to compression or shear. In many applications, it is important to know when powders are yielding, i.e. when they start to flow under shear; in other cases it is necessary to know how much stress is needed to keep them flowing. The measurement of powder yield and flow properties is still a challenge and will be addressed in this study.In the framework of the collaborative project T-MAPPP, a large set of shear experiments using different shear devices, namely the Jenike shear tester, the ELE direct shear tester, the Schulze ring shear tester and the FT4 powder rheometer, have been carried out on eight chemically-identical limestone powders of different particle sizes in a wide range of confining stresses. These experiments serve two goals: i) to test the reproducibility/consistency among different shear devices and testing protocols; ii) to relate the bulk behaviour to microscopic particle properties, focusing on the effect of particle size and thus inter-particle cohesion.The experiments show high repeatability for all shear devices, though some of them show more fluctuations than others. All devices provide consistent results, where the FT4 powder rheometer gives lower yield/steady state stress values, due to a different pre-shearing protocol. As expected, the bulk cohesion decreases with increasing particle size (up to 150 μm), due to the decrease of inter-particle cohesion. The bulk friction, characterized in different ways, is following a similar decreasing trend, whereas the bulk density increases with particle size in this range. Interestingly, for samples with particle sizes larger than 150 μm, the bulk cohesion increases slightly, while the bulk friction increases considerably—presumably due to particle interlocking effects—up to magnitudes comparable to those of the finest powders. Furthermore, removing the fines from the coarse powder samples reduces the bulk cohesion and bulk density, but has a negligible effect on the bulk friction.In addition to providing useful insights into the role of microscopically attractive, van der Waals, gravitational and/or compressive forces for the macroscopic bulk powder flow behaviour, the experimental data provide a robust database of cohesive and frictional fine powders for industrially relevant designs such as silos, as well as for calibration and validation of models and computer simulations.

Binder jetting is known to produce porous objects by depositing the binder selectively layer by layer on a powder bed. In this study, the pore size of printed parts and the correlating mechanical properties are investigated on a commercially available PMMA powder binder system. Pore sizes are measured via capillary flow porometry and mechanical properties via tensile tests. Porometry indicates that the pore size stays at a constant level of 22 µm at 5 to 10 wt% binder loading before decreasing to 6 µm at loadings of 30 wt% or higher. The results were compared with the mechanical testing and related to the agglomerate strength model of Rumpf. The highlights of the article are the application of a binder jetted part as a filter and the identification of a close relationship between porosity and mechanical strength, similar to phenomena in agglomeration science.

The global use of lithium-ion batteries of all types has been increasing at a rapid pace for many years. In order to achieve the goal of an economical and sustainable battery industry, the recycling and recirculation of materials is a central element on this path. As the achievement of high 95% recovery rates demanded by the European Union for some metals from today’s lithium ion batteries is already very challenging, the question arises of how the process chains and safety of battery recycling as well as the achievement of closed material cycles are affected by the new lithium battery generations, which are supposed to enter the market in the next 5 to 10 years. Based on a survey of the potential development of battery technology in the next years, where a diversification between high-performance and cost-efficient batteries is expected, and today’s knowledge on recycling, the challenges and chances of the new battery generations regarding the development of recycling processes, hazards in battery dismantling and recycling, as well as establishing a circular economy are discussed. It becomes clear that the diversification and new developments demand a proper separation of battery types before recycling, for example by a transnational network of dismantling and sorting locations, and flexible and high sophisticated recycling processes with case-wise higher safety standards than today. Moreover, for the low-cost batteries, recycling of the batteries becomes economically unattractive, so legal stipulations become important. However, in general, it must be still secured that closing the material cycle for all battery types with suitable processes is achieved to secure the supply of raw materials and also to further advance new developments.

Product fineness during grinding in stirred media mills is mainly influenced by the specific energy input, the stress energy transferred by the colliding grinding media and the stress frequency. The stress energy from grinding media collisions is heterogeneously distributed in stirred media mills. Herein, in order to characterize the stress energy distribution and the local grinding media collision frequencies, the grinding media motion was calculated using discrete element method (DEM) simulations coupled with computational fluid dynamics (CFD). The local grinding media concentration, velocity profiles, grinding media collisions and stress energies were compared for varied total grinding media fillings and stirrer speeds. It was confirmed that the normalized grinding media velocity profile can be used to divide the grinding chamber into four types of zones that allow the modeling of the stress energy distribution. However, the collision frequency showed very different distributions for varied stirrer velocities and grinding media fillings.

Internal short-circuit tests were carried out in a battery safety investigation chamber to determine the behavior of batteries during the nail penetration test. So far, systematic investigations regarding the test setup and its influence are rarely found in the literature. Especially, to improve the comparability of the multitude of available results, it is essential to understand the effects of the geometric, operating and ambient parameters. In this study commercial lithium ion batteries with a capacity of 5.3 and 3.3 Ah were used to study the influence of the varied parameters on the voltage drop, the development of surface temperatures and of infrared active gas species. We studied both the influence of the geometry of the penetrating nail and concentration of water in the inert atmosphere especially on the quantities of the reaction products under variation of cell capacity. It could be shown that the geometry of the nail, within certain limits, has no influence on the processes of the thermal runaway of high energy density lithium ion batteries (LIBs). However, a change in capacity from 5.3 to 3.3 Ah shows that in particular the gaseous reaction products differ: The standardized gas concentrations show a higher measurable concentration of all gases except CO for the 3.3 Ah LIBs. This circumstance can be explained by the intensity of the reactions due to the different battery capacities: In the 5.3 Ah cells a larger amount of unreacted material is immediately discharged from the reaction center, and by the different available amounts of oxidizing reaction partners. An increase of the water content in the surrounding atmosphere during the thermal runaway leads to a reduction of the measurable gas concentrations of up to 36.01%. In general, all measured concentrations decrease. With increased water content more reaction products from the atmosphere can be directly bound or settle as condensate on surfaces.

In all production processes of solid dosage forms, powders with a multitude of distributed properties must be processed [...]

Nanoparticles significantly alter the rheological properties of a polymer or monomeric resin with major effect on the further processing of the materials. In this matter, especially the influence of particle material and disperse properties on the viscosity is not yet understood fully, but can only be modelled to some extent empirically after extensive experimental effort. In this paper, a numerical study on an uncured monomeric epoxy resin, which is filled with boehmite nanoparticles, is presented to elucidate the working principles, which govern the rheological behavior of nanoparticulate suspensions and to simulate the suspension viscosity based on assessable material and system properties. To account for the effect of particle surface forces and hydrodynamic interactions on the rheological behavior, a resolved CFD is coupled with DEM. It can be shown that the particle interactions caused by surface forces induce velocity differences between the particles and their surrounding fluid, which result in increased drag forces and cause the additional energy dissipation during shearing. The paper points out the limits of the used simulation method and presents a correction technique with respect to the Péclet number, which broadens the range of applicability. Valuable information is gained for a future mechanistic modelling of nanoparticulate suspension viscosity by elucidating the interdependency between surface forces, shear rate and resulting drag forces on the particles.

The particle size reduction of active pharmaceutical ingredients is an efficient method to overcome challenges associated with a poor aqueous solubility. With respect to stability and patient’s convenience, the corresponding nanosuspensions are often further processed to solid dosage forms. In this regard, the influence of several formulation parameters (i.e., type of carrier material, type and amount of additional polymeric drying excipient in the nanosuspension) on the redispersibility of naproxen nanoparticle-loaded granules produced in a fluidized bed process was investigated. The dissolution rate of the carrier material (i.e., sucrose, mannitol, or lactose) was identified as a relevant material property, with higher dissolution rates (sucrose > mannitol > lactose) resulting in better redispersibility of the products. Additionally, the redispersibility of the product granules was observed to improve with increasing amounts of polymeric drying excipient in the nanosuspension. The redispersibility was observed to qualitatively correlate with the degree of nanoparticle embedding on the surface of the corresponding granules. This embedding was assumed to be either caused by a partial dissolution and subsequent resolidification of the carrier surface dependent on the dissolution rate of the carrier material or by resolidification of the dissolved polymeric drying excipient upon drying. As the correlation between the redispersibility and the morphology of the corresponding granules was observed for all investigated formulation parameters, it may be assumed that the redispersibility of the nanoparticles is determined by their distance in the dried state.

Paddle feeders are devices commonly used in rotary tablet presses to facilitate constant and efficient die filling. Adversely, the shear stress applied by the rotating paddles is known to affect the bulk properties of the processed powder dependent on the residence time. This study focuses on the residence time distribution (RTD) of two commonly applied excipients (microcrystalline cellulose, MCC; dicalcium phosphate, DCP), which exhibit different flow properties inside rotary tablet presses. To realistically depict the powder flow inside rotary tablet presses, custom-made tracer powder was developed. The applied method was proven to be appropriate as the tracer and bulk powder showed comparable properties. The RTDs of both materials were examined in two differently scaled rotary tablet presses and the influence of process parameters was determined. To analyze RTDs independent of the mass flow, the normalized variance was used to quantify intermixing. Substantial differences between both materials and tablet presses were found. Broader RTDs were measured for the poorer flowing MCC as well as for the production scale press. The obtained results can be used to improve the general understanding of powder flow inside rotary tablet presses and amplify scale-up and continuous production process development.

For the efficient and safe production of pharmaceutical tablets, a deep process understanding is of high importance. An essential process step during tableting is the die filling, as it is responsible for a consistent tablet weight and drug content. Furthermore, it affects the results of subsequent process steps, compaction and ejection, and thus critical quality attributes. This study focuses on understanding the influences of process parameters and material properties on die filling on a rotary tablet press. By the systematic variation in process parameters as the turret and paddle speeds as well as the fill and dosing depths, five formulations with differing properties are processed. Analysis of the normalized tablet weight, called filling yield, revealed different limitation mechanisms of the filling process, i.e., incomplete filled dies for certain parameter settings. Kinetic limitations occur due to a short residence time under the feed frame (filling time) caused by high turret speeds, which additionally induce high tablet weight variation coefficients. Characteristic maximum turret speeds at certain paddle speeds can be found to still achieve complete filling. At low turret speeds, densification of the powder inside the dies takes place, induced by two mechanisms: either high paddle speeds or high overfill ratios, or a combination of both. The challenge to fill the dies completely as well as avoid densification is dependent on material properties as the flowability. The mass discharge rate from an orifice was found to be in a linear correlation to the filling results of different formulations below complete filling.