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Nowadays, a growing offering of plant-based meat alternatives is available in the food market. Technologically, these products are produced through high-moisture shear technology. Process settings and material composition have a significant impact on the physicochemical characteristics of the final products. Throughout the process, the unfolded protein chains may be reduced, or associate in larger structures, creating rearrangement and cross-linking during the cooling stage. Generally, soy and pea proteins are the most used ingredients in plant-based meat analogues. Nevertheless, these proteins have shown poorer results with respect to the typical fibrousness and juiciness found in real meat. To address this limitation, wheat gluten is often incorporated into the formulations. This literature review highlights the key role of wheat gluten in creating products with higher anisotropy. The generation of new disulfide bonds after the addition of wheat gluten is critical to achieve the sought-after fibrous texture, whereas its incompatibility with the other protein phase present in the system is critical for the structuring process. However, allergenicity problems related to wheat gluten require alternatives, hence an evaluation of underutilized plant-based proteins has been carried out to identify those that potentially can imitate wheat gluten behavior during high-moisture shear processing. [ABSTRACT FROM AUTHOR]

The design of new technology for processing and manufacturing particulate products requires understanding granular rheology over a broad range of conditions. Powders display a complex behaviour due to their ability to rearrange under stress, and as a result, granular flow is generally classified into three flow regimes, namely a quasi-static regime dominated by frictional contacts, an inertial regime dominated by collisional and kinematic stresses and an intermediate regime where the three sources of stress are important to establish a stress-strain rate relationship. Characterisation of the flowability is generally restricted to the flow initiation in quasi-static regime, even if, transition into inertial conditions is very common in practical applications involving the control of dense flows, such as powder handling, particle formation processes or additive manufacturing. This work presents a critical review of available techniques to characterise the departure from the quasi-static regime into an intermediate flow. We revise the application of shear cells and present different strategies to modify classic devices with external actuation, such as aeration, to operate at higher inertial numbers. We pay particular attention to innovative designs using aerated Couette flow configurations, highlight the complexity in the standardisation and the challenges in advancing towards a universal model.

Purpose: The aim of this study was to compare the bulk lactose flow behavior with a defined fraction with smaller particles obtained by sieving from the bulk lactose and to evaluate the effect of a glidant addition on both samples. These powders showed, in a previous work, similar flow indexes (ffc) that motivated the addition of colloidal silicon dioxide in order to observe if there were any changes in their flow behaviors. Methods: To evaluate this effect on the diluent flow behavior, the methods described in the European Pharmacopeia were used. Results: The results obtained from conventional methods and shear cell methods (using the Powder Flow Tester) were compared, and they showed evident differences in the bulk and tapped densities values and flow classifications. The lactose monohydrate (FTotal) and lactose with particles smaller than 63 μm (F < 63) analyzed in a previous study presented similar ffc. To these pure powders a glidant was added, in increasing proportion (0.25—1.00%). The results obtained for all powders with colloidal silicon dioxide showed an improvement in its flow behaviors in comparison with pure powders. Conclusion: All the parameters studied showed an evident effect of the glidant used. For the same amount of glidant, the F < 63 presented worse flow profiles than FTotal because its particles have a larger surface area. The FTotal + 0.25 flow profile was more similar to the F < 63 + 0.50 flow profile than F < 63 + 0.25 flow profile. For both powders, the maximum amount of glidant that produces effect was 1.00% for F < 63 and 0.75% for FTotal, respectively. In all powders, the occurrence of caking was not observed. [ABSTRACT FROM AUTHOR]

This review discusses the use of starch in plant‐based meat replacing products. Starch is often added to meat and meat replacing products as a functional ingredient. The function of starch in those applications is investigated to be able to describe how it affects the production and structuring process as well as product properties. Often modified starch is used in these products, because of its improved functionality compared to native starch. Next to that, starch can also be present in meat replacing products as part of other ingredients, for example, when using legume or cereal meals or concentrates. It is discussed if this endogenous starch can have similar functionality and if not, whether it can be modified in a similar way as industrially modified starch. A new perspective on endogenous starch is proposed, demonstrating options for in situ modifications and promoting the use of less‐refined and therefore more sustainable ingredients in fibrous meat replacing products. [ABSTRACT FROM AUTHOR]

The objective of this work was to analyze the flow behavior of a commonly used filler (pregelatinised starch) and the effect of two of the most used lubricants (talc and colloidal silicon dioxide). The studies were carried out according to the conventional methods (Angle of Repose, Bulk and Tapped densities and from these the Compressibility Index) and shear cell methods (Brookfield Powder Flow Tester apparatus) described in European Pharmacopeia (Ph. Eur.). The results showed some surprising and unexpected values for the flow behavior of this filler under influence of the methods and the used glidants. Regarding pure starch and mixtures containing talc, the flow behavior was similar between them and the Flow Index (ffc) values varied between 1.8 and 4 (very cohesive and cohesive) as consolidation stress (σ1) increased. In this case, the glidant effect was not observed. However, for the mixtures of starch with colloidal silicon dioxide this effect was observed providing Flow Index (ffc) values between 2.6 and 8.9 (cohesive and easy-flowing) as consolidation stress (σ1) increased. Other parameters that are also used to characterize flow properties, more specifically, within silos, chutes and hoppers, such as effective angle of internal friction (φe), effective angle of wall friction (φx), critical arching and critical rathole values, provided similar information. Based in the obtained results from all tests it can be said that the talc did not induce improvement on the starch flow behavior in the used conditions in opposition to the effect produced by colloidal silicon dioxide. Example 1. A good flowability of powders is needed in order to be compressed/filled; Example 2. The overcome the poor flow it is usual to use glidants; Example 3. CSD improved the pregelatinised starch (Starch 1500®) flow; Example 4. Talc do not have relevant effect in the pregelatinised starch (Starch 1500®) flow; Example 5. Powder FlowTester method showed more complete and consistent results. [ABSTRACT FROM AUTHOR]

Tablet sticking, a phenomenon in which material adheres to the surface of tablet-punch face, is an ongoing and costly problem in pharmaceutical manufacturing, and is a significant issue for drug-product formulators. Here, it was hypothesized that the underlying cause of this phenomenon is due to intermolecular interactions between punch face and drug molecules. The present study evaluates powder rheology as a potential predictive technique for these interactions between the Active Pharmaceutical Ingredient (API) and punch face. In this study, we describe a series of powder rheology experiments to estimate the sticking tendencies of five model drugs to five different tablet punch metals. The results have shown that this approach was able to differentiate the five model drugs based on their sticking propensity to each punch metal used. Furthermore, the predicted sticking tendency rank order of the drugs obtained from powder rheology technique was validated by compression studies. The present work highlights powder rheology as a potential technique for predicting tablet sticking during research and development stage. A series of powder rheology experiments was conducted to estimate and predict sticking tendencies of five Active Pharmaceutical Ingredients to five different tablet punch metals. [Display omitted] • Intermolecular interactions between drug and punch initiates tablet sticking. • Powder rheology can be used as a predictive R&D technique for tablet sticking. • Tablet sticking is both drug, and metal surface specific. • Chromium punches are ineffective in reducing tablet sticking for certain APIs. [ABSTRACT FROM AUTHOR]

Purpose: Understanding and predicting the flow of bulk pharmaceutical materials could be key in enabling pharmaceutical manufacturing by continuous direct compression (CDC). This study examines whether, by taking powder and bulk measurements, and using statistical modelling, it would be possible to predict the flow of a range of materials likely to be used in CDC. Methods: More than 100 materials were selected for study, from four pharmaceutical companies. Particle properties were measured by static image analysis, powder surface area and surface energy techniques, and flow by shear cell measurements. The data was then analysed, and a range of statistical modelling techniques were used to build predictive models for flow. Results: Using the results from static image analysis, a model could be built which allowed the prediction of likely flow in a shear cell, which can be related to performance in a CDC system. Only a small amount of powder was required for the image analysis. Surface area did not add to the precision of the model, and the available surface energy technique did not correlate with flow. Conclusions: A small sample of powder can be examined by static image analysis, and this data can be used to give an early read on likely flow of a material in a CDC system or other pharmaceutical process, allowing early intervention (if necessary) to improve the characteristics of a material, early in development. [ABSTRACT FROM AUTHOR]

The design of new technology for processing and manufacturing particulate products requires understanding granular rheology over a broad range of conditions. Powders display a complex behaviour due to their ability to rearrange under stress, and as a result, granular flow is generally classified into three flow regimes, namely a quasi-static regime dominated by frictional contacts, an inertial regime dominated by collisional and kinematic stresses and an intermediate regime where the three sources of stress are important to establish a stress-strain rate relationship. Characterisation of the flowability is generally restricted to the flow initiation in quasi-static regime, even if, transition into inertial conditions is very common in practical applications involving the control of dense flows, such as powder handling, particle formation processes or additive manufacturing. This work presents a critical review of available techniques to characterise the departure from the quasi-static regime into an intermediate flow. We revise the application of shear cells and present different strategies to modify classic devices with external actuation, such as aeration, to operate at higher inertial numbers. We pay particular attention to innovative designs using aerated Couette flow configurations, highlight the complexity in the standardisation and the challenges in advancing towards a universal model. [ABSTRACT FROM AUTHOR]

Discharge behavior of powders is crucial for pharmaceuticals and other industrial branches. However, for small particle sizes, the influence of the surrounding fluid can lead to unsteady and unexpected mass flow rates. For detailed insight during powder discharge, a CFD-DEM study was carried out for a cohesive lactose powder. Firstly, calibration of DEM parameters was conducted with nanoindentation, free fall experiments, friction tests and angle of repose measurements. Further validation was achieved by shear tests and powder rheometry. Subsequently, experimental and numerical discharge procedures were performed for a wedge-shaped silo with varying configurations. Bed expansion inside the silo led to a vacuum in the hopper, which reduced the discharge rate. The mass flow rate in experiments and CFD-DEM simulations showed only low sensitivity to hopper angle variation. For flat hopper angles, relative air flow extended horizontally to stagnant zones, which acted as a permeable hopper and reduced the air impairment. Unlabelled Image • Extensive DEM model calibration achieved realistic powder flow behavior. • Air impairment of powder discharge by interstitial air is dependent on hopper angle. • Dead zones act as permeable hopper, decreasing the vertical pressure gradient. • Steeper hoppers lead to higher pressure gradients which balances the flow rate. • The stagnant zone angle increased with decreasing surcharge level. [ABSTRACT FROM AUTHOR]

Shear cell tests have been conducted on twenty different lactose powders, most of which commercially available for oral or inhalation purposes, spanning a wide range of particle sizes, particle morphologies, production processes. The aims of the investigation were: i) to verify the reliability of the technique in evaluating and classifying the flowability of powders; ii) to understand the connection between the flowability of a powder and the morphological properties of its particles; iii) to find a general mathematical relationship able to predict the yield locus shape given the particle size, shape and consolidation state of a lactose powder. These aspects and their limitations are detailed in the manuscript together with other interesting findings on the stick-slip behavior observed in most of the lactose powders examined. Unlabelled Image • 16 different lactose powders investigated in detail using shear cell tests. • The variability of the shear cell results was investigated and reduced. • A formula to predict the yield locus at a given consolidation state was provided. • Stick-slip oscillations in lactose powders were detected and analyzed in detail. [ABSTRACT FROM AUTHOR]

The flow properties of pharmaceutical powders have a great importance in the manufacturing of solid dosage forms. In order to ensure the performance in the production line this parameter must be determined. There are several methods described in European Pharmacopeia that are used to measure these properties. Some of them were used in this study and the results obtained from conventional methods (Conv) and shear cell using the powder flow tester (PFT) showed differences that were more evident in fractions with smaller particle size (F < 63) and for bulk powder (FTotal). The various powder behaviors showed to be related with the size of the particles. An increase of the ffc (Flow Index) was observed with the increase of the particle size. It was also found for the different fractions that the ffc always increases with increasing major principal consolidation stress (σ1). This study shown to be predictive because it also allowed the behavior profiles of other LactMN fractions to be known by interpolation of the median size (Dv50) or σ1 values ranged between the studied intervals. Furthermore, it was also observed that ffc of the FTotal was similar to the F < 63, showing the same behavior under σ1. The occurrence of caking was not observed. [ABSTRACT FROM AUTHOR]

Multiple pharmaceutical powder processes operate at stresses lower than utilized in typical lab-scale shear cell testing. To bridge this gap, we developed a method to determine intrinsic powder flow properties, in particular, flow function (FF c), under such low stresses. A simple, commercially-available flow-through-orifice device (Flodex™ apparatus) was selected. By developing a theoretical framework using Jenike's radial stress field analysis, the major principal stress and FF c of the tested powder can be derived from the otherwise empirical "Flodex" experiment. This method was applied to 10 distinct pharmaceutical powders. The major principal stresses associated with the test were estimated to be in the order of 100 Pa, significantly lower than what is achievable using shear cell-based methods. The resulting FF c values are generally consistent with the data extrapolated from ring shear testing. We showed that for pharmaceutical powders, FF c decreases with decreasing consolidation stress, but the values are always greater than 1. Therefore, the threshold for poor/acceptable flowability (by FF c) should be used with caution at low-stress conditions. Through this work, we showed that by integrating the radial stress field theory with a simple flow-through-orifice experiment, intrinsic powder flow properties under low stresses could be reliably determined. [ABSTRACT FROM AUTHOR]

There is an ongoing search for sustainable and functional alternative protein sources to animal proteins. Methylobacillus flagellatus (grown on renewable methanol) is known to give high protein yields with low resource requirements. However, the techno-functionality for food applications has not yet been explored. In this study, the biomass was processed by microfluidizer, centrifugation and acid precipitation. Unprocessed biomass (UB: protein content of 73 %) and processed biomass fractions were investigated on their composition, physicochemical and rheological properties. All the biomass fractions had comparable composition, a pink, meat-like colour and umami smell. Differences were observed in the rheological and structuring properties using shear cell: UB yielded layered but crumbly structure, while the acid precipitated fraction resulted in a firm consistent product. From a functional point of view, M. flagellatus is a promising protein source that can be used for meat analogues without extensive prior fractionation. [Display omitted] • M. flagellatus can be grown to high cell densities with methanol. • M. flagellatus biomass has pinkish colour. • A high protein content of 70 % was found in all biomass fractions. • Rheological properties were enhanced after acid precipitation. • Layered meat analogues could be produced with unprocessed biomass. [ABSTRACT FROM AUTHOR]

Interdiffusion coefficients are key parameters for the solidification process of liquid alloys. However, the determination of interdiffusion coefficients in liquid metals at high temperatures is a challenging and extensive task, due to a variety of potential systematic errors. In recent years we have developed an X-ray in situ shear cell method for the measurement of interdiffusion coefficients in binary metallic melts. This technique enables the monitoring of the experiment in order to exclude fatal errors. Utilizing X-ray contrast, the method also provides a time-resolved concentration distribution. Such an in situ data set contains significantly more information than ex situ evaluated experiments. Available analyzing strategies do not fully exploit this potential yet. We present three new analyzing approaches that are able to retrieve a concentration-dependent interdiffusion coefficient from only one in situ data set. In that way, larger concentration differences become accessible for an experiment, which considerably decreases efforts. Using simulations, the approaches are checked for robustness. Furthermore, the approaches are run on real in situ data from a binary (0 to 9 at% Au-content) Al–Au alloy at 1000 °C which results in a concentration-dependent interdiffusion coefficient within the measured concentration range.

At moderate stresses, shear cells are the preferred method of powder flow measurement. However, several industrial processes operate at low stresses, where the determination of unconfined yield strength by the shear cell technique may be inconsistent, or found not to correlate with observed behaviour. Alternatively, ball indentation can be used, which directly measures hardness; related to unconfined yield strength by the constraint factor. However, it is not known how constraint factor is influenced by particle properties. Here, ball indentation and shear cell methods are applied for glass beads of various size distributions, and the influence of particle size distribution on the constraint factor is explored. The constraint factor is shown to be independent of the pre-consolidation stress, though reduces as the d 10 , d 50 or d 90 are increased. Unconfined yield strength inferred from indentation measurements suggest that extrapolation of shear cell data to low stresses overestimates the unconfined yield strength. Unlabelled Image • Extrapolating shear cell data from high to low stress overestimates yield strength. • Ball indentation measures hardness; equal to yield strength times constraint factor. • Constraint factor is independent of applied stress. • Constraint factor decreases with increasing particle size and distribution width. • Constraint factor increases with fines content, though reduces with added coarse. [ABSTRACT FROM AUTHOR]

The powders used in the production of solid dosage forms must have ability to flow that allows their industrial processing. Although this property has been studied for most of the powders, in this study non-expected flow behaviors were observed for the model excipient used, Microcrystalline Cellulose (MCC). Several fractions with different sizes were fractioned by sieving of the model excipient and its flow behaviors were analyzed by different methods. The shear cell results showed an increase of the flowability index (ffc) with the increase of the particle size and consolidation stress. Some related information has been referenced in the literature, however, in this work it was shown for different size fractions that the ffc decreased above a certain consolidation stress value (2000–4000 N/m2). The explanation of this phenomenon is based on the increase of cohesion. Furthermore, it was also observed that the fractions with sizes between 125–180 µm present a ffc higher than bulk powder (FTotal) with similar percentile (DV50) indicating that this index is dependent on the size of the particles and also on its size distribution range. Thus, it can be affirmed that more homogeneous samples in size and with a narrower distribution present a better ffc. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Flowability is a key consideration during the formulation and process development of oral solid dosage forms as it can have a critical impact on product quality. With a limited number of examples available in the literature, there is a need to better understand and share the typical flow properties of pharmaceutical materials. Here, historical data (3909 experiments) from a shear cell apparatus were extracted and analysed. These data were composed of different material types, including APIs, excipients, blends and granules from nearly a decade of development projects. APIs were found to have poor flow properties (ff c <2), while other materials (excipients, blends and granules) generally had good flow properties. This analysis provided an enhanced understanding of the typical flow properties of pharmaceutical materials. By combining these data with information on the process and achieved drug load, it was possible to characterise our current operating space as a process flow map which could be used to focus future development. [ABSTRACT FROM AUTHOR]

Abstract We present herein a comprehensive methodology to evaluate the risks involved in gravity-driven flow of pharmaceutical powders, including mass flow/funnel flow pattern, arch formation under active stress state (initial discharging) and passive stress state (following initial discharging), and rathole formation. Built on original theories underpinning the hopper design procedure, the methodology was modified to accommodate practices of pharmaceutical powder handling. All data required are generated from conventional ring shear tester. We applied the methodology to evaluate the powder flow risks during drug product manufacturing campaigns, where two powder blends with distinct flow behavior were discharged from a 200-L bin. The predicted results are in agreement with experiments where visual observations were possible, including the flow pattern, arch formation under active stress state, and rathole formation. One notable discovery is that pharmaceutical powders exhibit high risk of arch formation under active stress state, because of the exceeding major principal stress than the passive state. This phenomenon has been so far overlooked and the existing flow function-based classification cannot capture this risk. We propose, through this methodology, that reliable powder flow assessment should consider factors preventing flow (i.e., flow function), as well as factors facilitating flow (i.e., external stress). [ABSTRACT FROM AUTHOR]

Abstract In this study, we have investigated the impact of repeated shear displacement on powder flow properties. We show that when multiple yield loci are obtained using the same bulk solid specimen by stepping through different stress levels (i.e., stress walk [SW]), the shear deformation of the powder in a rotational shear cell, that is, Schulze Ring Shear Tester, is maximized, reducing the powder shear strength. This approach is material and time sparing; however, it imprecisely predicts better powder flowability. The magnitude of the change in the unconfined yield strength, σ c , due to this prolonged shear displacement appears to be material-dependent, being less impactful for free-flowing powders. Using the SW and the individual yield loci-generated flow properties, we have demonstrated that in hopper design, the shear displacement effect impacts the computed critical arching diameter more than the critical mass flow angle. This knowledge of powder flow properties highlights limitations associated with the SW. An exponential function was found to describe the relationship between the change in σ c at the highest major principal stress and the density weighted flowability, ff ρ , with an R 2 of 0.98. Such a model could be a valuable tool for correcting shear strength results obtained from SW, saving time, and material. [ABSTRACT FROM AUTHOR]

A comparative analysis was conducted to examine the flow characteristics of two HPMC grades and their fractions. Excipients processing contains critical steps in the manufacturing of solid dosage forms and therefore it is essential to determine their flowability. Flow characterization was done using conventional and shear cell methods. After the division into different particles size, HPMC2910 showed an increase of the ff c for the fractions with the largest particle size and HPMC2208 showed an unprecedented result for the fraction with the smallest size. Thus, for this excipient, the best ff c was obtained with the fraction containing the smallest particles which surprisingly contradicted the literature (shape effect overlapped the size effect). It was also found for different fractions that the ff c increased with the increasing of the σ 1 , showing in some of them a decrease of the same from a certain σ 1 value. Furthermore, caking was not observed in both cases. [Display omitted] • Excipients flow characterization is a critical step in the pharmaceutical development. • Particle shape and size can have an additive or contradictory effect on powder flow. • The shear cell method provides results more rigorous and reliable. • Flow index (ff c) depends on the particle size and shape. • The decreased of particle size does not always worsen the powder flow. [ABSTRACT FROM AUTHOR]

The purpose of this study was to demonstrate that the flow function (FFc) of pharmaceutical powders, as measured by rotational shear cell, is predominantly governed by cohesion but not friction coefficients. Driven by an earlier report showing an inverse correlation between FFc and the cohesion divided by the corresponding pre-consolidation stress (Wang et al. 2016. Powder Tech . 294:105-112), we performed analysis on a large data set containing 1130 measurements from a ring shear tester and identified a near-perfect inverse correlation between the FFc and cohesion. Conversely, no correlation was found between FFc and friction angles. We also conducted theoretical analysis and estimated such correlations based on Mohr–Coulomb failure model. We discovered that the correlation between FFc and cohesion can sustain as long as the angle of internal friction at incipient flow is not significantly larger than the angle of internal friction at steady-state flow, a condition covering almost all pharmaceutical powders. The outcome of this study bears significance in pharmaceutical development. Because the cohesion value is strongly influenced by the interparticle cohesive forces, this study effectively shows that it is more efficient to improve the pharmaceutical powder flow by lowering the interparticle cohesive forces than by lowering the interparticle frictions. [ABSTRACT FROM AUTHOR]

Air entrapment efficiency of the powders is one of the main factors leading to occurrence of capping or lamination tendency of tablets manufactured from the directly compressible powder blends. The purpose of the current research was to study this underlying cause leading to occurrence of capping or lamination of tablets through evaluation of powder rheological properties. Powder blends were prepared by addition of 0% w/ w to 100% w/ w of individual active pharmaceutical ingredient (API) [two model API: acetaminophen (APAP) and ibuprofen (IBU)] with microcrystalline cellulose without and with 0.5% w/ w Magnesium Stearate as lubricant. Powder rheological properties were analyzed using FT4 Powder Rheometer for dynamic, bulk, and shear properties. Tablet mechanical properties of the respective blends were studied by determining the ability of the material to form tablet of specific strength under applied compaction pressure through tabletability profile. The results showed that powder rheometer distinguished the powder blends based on their ability to relieve entrapped air along with the distinctive flow characteristics. Powder blend prepared with increasing addition of APAP displayed low powder permeability as compared to IBU blends with better powder permeability, compressibility and flow characteristics. Also, lubrication of the APAP blends did not ease their ability to relieve air. Tabletability profiles revealed the potential occurrence of capping or lamination in tablets prepared from the powder blends with high APAP content. This study can help scientist to understand tableting performance at the early-developmental stages and can avoid occurrence capping and lamination of tablets. [ABSTRACT FROM AUTHOR]