Investigation of mass discharge rate and segregation from hopper by discrete element method

Hoppers of different shape and angle are widely used in different industries particularly in handling of solids as storage units and in unit operations, e.g. mixing, tableting, etc. It is a challenge to choose a right hopper to achieve desired flow and insignificant segregation due to difference in material properties. General approach for the selection of optimum hopper for a given unit operation is based on the trial-and-error experimental approach. To address this optimum hopper selection, combined experimental and numerical approach is presented in this study. The objective of this study is to analyze the effect of mixture composition and hopper angle on the flow rate and segregation behavior. The numerical simulation of granular flow out of various conical hoppers was also performed using the discrete element method (DEM). The materials considered include different particle size glass bead particles in different proportions by mass. The experimental study is done to validate the DEM results, particularly, mass flow rate. The results analyzed include temporal development of mass fraction of a given particle size during discharge. In addition, the mass flow rate is also computed. The results indicate that fines percentage in the mixture, ratio of smallest particle size to largest in the mixture, and hopper angle plays significant role in determining the segregation and mass flow rate. The flow pattern found to be influenced by the hopper angle and mean particle size of mixture. The results of discharge rate from DEM are also compared with existing empirical correlations and finite element method based elastoplastic model. The DEM prediction shows a good agreement with the existing correlations for a wide range of hopper angles, and with the experimental data

Numerical investigation of screw design influence on screw feeding in a roller compactor

Roller compaction refers to a dry granulation process where fine particulate feed is fed to the counter rotating rolls of a roller compactor to form ribbons which are further milled to produce free flowing agglomerates. For the continuous production of ribbons, there needs to be an adequate supply of powder by the screw to the rolls without any interruptions. In general, screws used in roller compactors are designed to convey powders of all types (cohesive, bulky, compressible, etc.), whereby usage of different screw designs for different powder types may be avoided. However, using such single screw type roller compactors for poor flowing powders may be challenging. On the other hand, the selection of the right screw for a given powder can only be done based on a combination of prior experience and trial-and-error experimentation. Empirical correlations exist to predict the draw down rate of screw feeders depending on their design, however, these correlations assume that there is continuous supply of powder by the screw, which limits its application to free-flowing powders only. To address this, in this study numerical simulations are performed based on discrete element method (DEM) to investigate the impact of screw design on the powder supply to rolls for cohesive and poorly flowing powders. The geometry considered includes a hopper, horizontal feeding screw below the hopper, and two counter-rotating rolls at the end of the screw. Two different screw designs are investigated where the main difference between them is the pitch length. The influence of scraper speed is investigated. Additionally, the influence of material attribute such as cohesion is studied. For both designs, the simulation results calculated include the rate of powder supply by the screw, velocity of particles in the screw etc. The simulation results of powder supply rate are also compared with results obtained based on empirical correlation. Overall, this simulation approach helps in selecting appropriate screw design for the given cohesive powder

Powder flow within a pharmaceutical tablet press – a DEM analysis

Numerical simulations in pharmaceutical industry are gaining importance as an advanced tool to elucidate the underlying physics in unit operations during tablet manufacturing. Out of different processing stages, powder flow within the tableting machine constitutes one critical step defining inter alia product safety in terms of content and content uniformity of the active pharmaceutical ingredient (API). By means of numerical simulations the Quality by Design (QbD) approach could be integrated to enhance product quality. However, the numerical simulations reported so far either evaluated the powder flow in a simplified system without considering the complex geometrical configuration within the rotary tablet press or used unrealistic micro-mechanical particle properties and sizes. This work presents a numerical approach for studying the powder flow within a force feeder to die/cavity in a rotary tablet press with actual dimensions to evaluate the final product quality. The computations were carried out using an open source discrete element method (DEM) code. The investigated system consists of a hopper, a force feeder comprising three rotating paddle wheels, and a turret with 24 dies. A poly-disperse particle size distribution was used mimicking a low dose direct compression formulation with calibrated micro-mechanical material properties. First of all, a summary of the basic metrics such particle size distribution and mass hold up in the different parts of the feeder is provided. Subsequently emphasis is given to the powder flow patterns in the force feeder that are visualized by particles’ coloring. Results reveal that (1) the powder feeding from the hopper into the feeder shows a gradient across the feeding hopper width causing an intriguing particle mixing, (2) particles are unequally refed from dosing wheel zone and (3) an intermixing between the reverse dosing and filling wheel zone can be identified. Those three visualized powder flow phenomena are supported by quantitative analysis and eventually their influence on the filled dies is being explained. In conclusion, this study helps in visualizing powder flow in a pharmaceutical tablet press disclosing astonishing particle flow phenomena that have not been reported yet

Quantitative Analysis of Glassy State Relaxation and Ostwald Ripening during Annealing Using Freeze-Drying Microscopy

Supercooling during the freezing of pharmaceutical solutions often leads to suboptimal freeze-drying results, such as long primary drying times or a collapse in the cake structure. Thermal treatment of the frozen solution, known as annealing, can improve those issues by influencing properties such as the pore size and collapse temperature of the lyophilisate. In this study we aimed to show that annealing causes a rearrangement of water molecules between ice crystals, as well as between the freeze-concentrated amorphous matrix and the crystalline ice phase in a frozen binary aqueous solution. Ice crystal sizes, as well as volume fractions of the crystalline and amorphous phases of 10% (w/w) sucrose and trehalose solutions, were quantified after annealing using freeze-drying microscopy and image labelling. Depending on the annealing time and temperature, the amorphous phase was shown to decrease its volume due to the crystallisation of vitreous water (i.e., glassy state relaxation) while the crystalline phase was undergoing coarsening (i.e., Ostwald ripening). These results allow, for the first time, a quantitative comparison of the two phenomena. It was demonstrated that glassy state relaxation and Ostwald ripening, although occurring simultaneously, are distinct processes that follow different kinetics

Numerical and Experimental Investigation of the Hydrodynamics in the Single-Use Bioreactor Mobius® CellReady 3 L

Two-way Euler-Lagrange simulations are performed to characterize the hydrodynamics in the single-use bioreactor Mobius® CellReady 3 L. The hydrodynamics in stirred tank bioreactors are frequently modeled with the Euler–Euler approach, which cannot capture the trajectories of single bubbles. The present study employs the two-way coupled Euler–Lagrange approach, which accounts for the individual bubble trajectories through Langrangian equations and considers their impact on the Eulerian liquid phase equations. Hydrodynamic process characteristics that are relevant for cell cultivation including the oxygen mass transfer coefficient, the mixing time, and the hydrodynamic stress are evaluated for different working volumes, sparger types, impeller speeds, and sparging rates. A microporous sparger and an open pipe sparger are considered where bubbles of different sizes are generated, which has a pronounced impact on the bubble dispersion and the volumetric oxygen mass transfer coefficient. It is found that only the microporous sparger provides sufficiently high oxygen transfer to support typical suspended mammalian cell lines. The simulated mixing time and the volumetric oxygen mass transfer coefficient are successfully validated with experimental results. Due to the small reactor size, mixing times are below 25 s across all tested conditions. For the highest sparging rate of 100 mL min−1, the mixing time is found to be two seconds shorter than for a sparging rate of 50 mL min−1, which again, is 0.1 s longer than for a sparging rate of 10 mL min−1 at the same impeller speed of 100 rpm and the working volume of 1.7 L. The hydrodynamic stress in this bioreactor is found to be below critical levels for all investigated impeller speeds of up to 150 rpm, where the maximum levels are found in the region where the bubbles pass behind the impeller blades

CFD-Based and Experimental Hydrodynamic Characterization of the Single-Use Bioreactor XcellerexTM XDR-10

Understanding the hydrodynamic conditions in bioreactors is of utmost importance for the selection of operating conditions during cell culture process development. In the present study, the two-phase flow in the lab-scale single-use bioreactor XcellerexTM XDR-10 is characterized for working volumes from 4.5 L to 10 L, impeller speeds from 40 rpm to 360 rpm, and sparging with two different microporous spargers at rates from 0.02 L min−1 to 0.5 L min−1. The numerical simulations are performed with the one-way coupled Euler–Lagrange and the Euler–Euler models. The results of the agitated liquid height, the mixing time, and the volumetric oxygen mass transfer coefficient are compared to experiments. For the unbaffled XDR-10, strong surface vortex formation is found for the maximum impeller speed. To support the selection of suitable impeller speeds for cell cultivation, the surface vortex formation, the average turbulence energy dissipation rate, the hydrodynamic stress, and the mixing time are analyzed and discussed. Surface vortex formation is observed for the maximum impeller speed. Mixing times are below 30 s across all conditions, and volumetric oxygen mass transfer coefficients of up to 22.1 h−1 are found. The XDR-10 provides hydrodynamic conditions which are well suited for the cultivation of animal cells, despite the unusual design of a single bottom-mounted impeller and an unbaffled cultivation bioreactor