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Fine grinding in wet stirred media mills is a key operation in numerous industrial processes. During wet milling, grinding beads (typically millimetre scale) collide with each other under rapid agitation. These collisions transfer energy into the surrounding medium, a feed stream comprising a premixed slurry (a suspension of micron-sized particles), leading to a reduced particle size. Numerical simulation provides an opportunity to gain mechanistic insight by modelling the influences of grinding media, agitator speed and slurry rheology on the breakage. The multiphase nature of wet milling necessitates models that account for both the solid grinding beads and the slurry feed. Established fluid-particle coupled methods are in principle capable of doing this, but the need to resolve the large hydrodynamic lubrication forces between near-contacting beads demands extremely high fluid field resolution, leading to proliferating simulation size and cost. To address this challenge, a Discrete Element Method (DEM) simulation for a lab scale mill is presented in which the bead-bead interaction includes pairwise hydrodynamic lubrication in addition to frictional contact forces. The model accounts for multiphase effects in a simplified yet physically well-motivated way, circumventing the computational cost of a fully fluid-resolved model. A systematic model calibration against the laboratory mill is presented, and thereafter the model provides a good estimation for the empirical power draw across the full range of rotation speeds and considered feed viscosities. The differences in energy dissipation modes and the local distribution of collisions along the mill chamber are examined for the extreme viscosity condition, revealing that most energy dissipation is due to inter-particle forces acting tangentially (shearing and rolling) while highly energetic collisions (impact and torsion), relying on free flows and inter-bead mobility, are relatively unimportant.

Processability of powders in high load compaction constitutes a challenge due to particle rearrangement, compression and breakage occurring simultaneously. Although tableting is a central operation in pharmaceutical technology, a better understanding of the link between the macroscopic powder behaviour and its micro-mechanical properties is still required. In the present study, a dual focus on the powder compaction behaviour and the quality properties of final tablets using a compaction simulator is presented. Tableting has been performed for a wide size range of limestone powders from 10 to 400 MPa, in order to understand and compare the powder compaction behaviour at both low and high confining stresses. Compactibility of limestone, the relation between porosity and stress, has been assessed with both the classical (logarithmic) Heckel model and the newly proposed (double logarithmic) Wunsch model, confirming the improvement of the latter to enhance the description of the porosity change during compaction, as well as the model robustness towards non-pharmaceutical powders. The qualitative effect of particle size and thus cohesion on the bulk density at high pressure compaction is found to be very similar to the low pressure regime. However, the geometrical interlocking influence of large size powders found in a previous study becomes irrelevant at such high pressures. For d 50 10 μm, the tablet tensile strength remains almost insensitive to the size variation. However, for the coarsest grades, the tensile strength decreases with increasing d 50 at all compaction stresses. In addition, the tablet tensile strength is found to follow a non-monotonic trend with median particle size.

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.

The goal of the present study is to assess the extent of particle rearrangement and the degree of anisotropy for uni-axial compaction of microcrystalline cellulose (MCC) by Discrete Element method simulations. The elasto-plastic cohesive hysteretic Edinburgh contact model is hereby considered. First, a calibration strategy for all required collisional, frictional, or cohesion input parameters is presented. A dual approach combining direct determination tests (e.g., nano-indentation or inverse gas chromatography) and indirect fitting tests (e.g., tumbling drum test) provides the final set of property values. Second, the uni-axial compaction of MCC for a range of target compaction pressures and different primary particle dispersities (mono- and polydisperse) is conducted. The anisotropic behavior of compaction is analyzed by computing averaged quantities such as the deviatoric term and the maximum difference between characteristic roots of the fabric tensor. The results depict a remaining degree of anisotropy after compaction, depending on the maximum compaction pressure and particle dispersity, which does not fully recover after powder decompression.

Powder densification through uniaxial compaction is governed by a number of simultaneous processes taking place on a reduced time as the result of the stress gradients within the packing, as well as the frictional and adhesive forces between the powder and the die walls. As a result of that, a density and stiffness anisotropy is developed across the axial and radial directions. In this study, microindentation has been applied to assess and quantify the variation of the module of elasticity ( E m o d ) throughout the surface of cylindrical tablets. A representative set of deformation behaviors was analyzed by pharmaceutical excipients ranging from soft/plastic behavior (microcrystalline cellulose) over medium (lactose) to hard/brittle behavior (calcium phosphate) for different compaction pressures. The results of the local stiffness distribution over tablet faces depicted a linear and directly proportional tendency between a solid fraction and E m o d for the upper and lower faces, as well as remarkable stiffness anisotropy between the axial and radial directions of compaction. The highest extent of the stiffness anisotropy that was found for ductile grades of microcrystalline cellulose (MCC) in comparison with brittle powders has been attributed to the dual phenomena of overall elastic recovery and Poisson&rsquo, s effect on the relaxation kinetics. As a reinforcement of this analysis, the evolution of the specific surface area elucidated the respective densification mechanism and its implementations toward anisotropy. For ductile excipients, the increase in the contact surface area as well as the reduction and closing of interstitial pores explain the reduction of surface area with increasing compaction pressure. For brittle powders, densification evolves through fragmentation and the subsequent filling of voids.

We present a methodology to characterize the 3D microstructure of Ibuprofen tablets, which strongly influences the strength and solubility kinetics of the final formulation, by means of synchrotron tomography. A physically coherent trinarization for greyscale images of Ibuprofen tablets consisting of the three phases microcrystalline cellulose, Ibuprofen and pores is presented. For this purpose, a hybrid approach is developed combining a trinarization by means of statistical learning with a trinarization based on a watershed algorithm. This hybrid approach allows us to compute microstructure characteristics of tablets using image analysis. A comparison with experimental results shows that there is a significant amount of pores which is below the resolution limit and results from image analysis let us conjecture that these pores make up the major part of the surface between pores and solid. Furthermore, we compute microstructure characteristics, which are experimentally not accessible such as local percolation probabilities and chord length distribution functions. Both characteristics are meaningful in order to quantify the influence of tablet compaction on its microstructure. The presented approach can be used to get better insights into the relationship between production parameters and microstructure characteristics based on 3D image data of Ibuprofen tablets manufactured under different conditions., Comment: 20 pages, 8 figures