Residence time distributions of different size particles in the spray zone of a Wurster fluid bed studied using DEM-CFD Liang Li1, 2, Johan Remmelgas2, *, Berend G.M. van Wachem3, Christian von Corswant2, Mats Johansson2, Staffan Folestad2, Anders Rasmuson1 1Department of Chemical and Biological Engineering, Chalmers University of Technology, SE-412 96, Gothenburg, Sweden 2Pharmaceutical 3Division Development, AstraZeneca R&D, Mölndal, Sweden of Thermofluids, Department of Mechanical Engineering, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom *Correspondence should be addressed to Johan Remmelgas at Tel +46-(0)-31-7065838 / Fax +46-(0)31-7763729 [email protected]. Abstract Particle cycle and residence time distributions in different regions, particularly in the spray zone, play an important role in fluid bed coating. In this study, a DEM-CFD (discrete element method, computational fluid dynamics) model is employed to determine particle cycle and residence time distributions in a laboratory-scale Wurster fluid bed coater. The calculations show good agreement with data obtained using the positron emission particle tracking (PEPT) technique. The DEM-CFD simulations of different size particles show that large particles spend a longer time in the spray zone and in the Wurster tube than small particles. In addition, large particles are found on average to move closer to the spray nozzle than small particles, which implies that the large particles could shield small particles from the spray droplets. Both of these effects suggest that large particles receive a greater amount of coating solution per unit area per cycle than small particles. However, the simulations in combination with the PEPT experiments show that this is partly compensated for by a longer cycle time for large particles. Large particles thus receive more coating per unit area per pass through the spray zone, but also travel through the spray zone less frequently than small particles. Keywords: fluid bed, coating, spray zone, residence time distribution, discrete element method 1 1. Introduction The Wurster process [1] has been widely used to coat particles in industry for a number of different purposes [2]. In the pharmaceutical industry it is used to coat tablets or pellets with drug substances or functional films that, e.g. control the release of the drug substance [3-6]. The process typically takes place in a fluid bed, as illustrated in Figure 1, in which particles are kept near minimum fluidization by a fluidization air flow that is supplied through a distributor plate at the bottom of the fluid bed. One or more twofluid nozzles located at the bottom of the bed supply an atomization air flow and a liquid suspension in the form of droplets. The liquid droplets are deposited onto the particles that pass through the spray zone. The particles are then dried by the air flow as they move upwards and as they settle back towards the bottom of the fluid bed. Figure 1 Schematic of the Wurster process and the different regions: 1) the spray zone, 2) the Wurster tube, 3) the fountain region, 4) the downbed region, and 5) the horizontal transport region. The fluid bed can be divided into different regions as shown in Figure 1 [7-9]. The particle coating cycle, i.e. the sequence of coating and subsequent drying, is also illustrated in Figure 1. It is here defined as the trajectory in which the particle travels through the spray zone, the Wurster tube, the fountain region and the downbed region before it reappears in the spray zone to begin the next coating cycle. The total amount of coating deposited onto a particle depends on the number of times the particle passes the spray zone and on the amount of coating solution that the particle receives per pass [1013]. Thus it is clear that the cycle time distribution (CTD) and the residence time distribution (RTD) in the spray zone of particles are important factors in determining the quality of the product such as the film thickness and the film thickness variability. Furthermore, the RTDs in different regions determine the drying rate of the particles in different regions, which plays a key role in the film formation process. There have been a number of experimental studies on CTDs and RTDs in previous work. Mann and Crosby [14] and Shelukar et al. [12] measured the CTDs using radioactive or magnetic particles in spouted beds and Wurster beds respectively, and San José et al. [15] investigated the CTDs by monitoring colored particles in spouted bed dryer. While the CTD certainly affects the amount of coating solution deposited onto the particles, the RTD in the spray zone and the detailed motion of particles in the spray zone also play an 2 important role. Moreover, it has been proposed that particles of one size receive a smaller portion of the coating solution due to shielding by particles of a different size. For example, Cheng and Turton [16] reported that the major cause of coating variation can be attributed to particles receiving different amounts of coating when passing through the spray zone. Recently, Li et al. [17] presented an experimental study of particle cycle and residence time distributions in different regions using the positron emission particle tracking (PEPT) technique. The results from the PEPT technique confirmed clear differences in the RTD for different size particles, also for mixtures of particles. Unfortunately, because of limitations with the PEPT technique the particle motion in the spray zone could only partially be characterized. Additional studies were therefore suggested by Li et al. [17] to provide further insight into the detailed particle motion in the spray zone and its contribution to particle coating process. In order to shed light on the detailed particle motion in the spray zone, DEM-CFD (discrete element method, computational fluid dynamics) modeling may be employed. In this modeling approach, every particle is modeled (as a discrete element) while the gas phase is treated as a continuum. When the number of particles is large, as is typical in particle coating processes, the computational time can become very long. For many particle coating systems used in the pharmaceutical industry, however, batch sizes of a few hundred grams are often employed during development. Depending on the particle size, these systems thus contain between tens of thousands and a few million particles. Simulations involving tens of thousands of particles are fairly straightforward, while simulations involving a few million particles are challenging but still feasible (see e.g. [18]). In the pharmaceutical industry, CFD-DEM modeling thus offers a unique opportunity to study process systems that are commonly used for small-scale production. The discrete element method was proposed for granular assemblies by Cundall and Strack [19] and was first introduced into research in fluid beds by Tsuji et al. [20]. The DEM-CFD approach is increasingly applied in modeling of particle/powder processes [21-29] and has become popular [30] because interparticle interactions are accounted for in a straightforward manner. For example, Link et al. [22] assessed the capability of DEM to reproduce several important flow regimes observed in a 3D spout-fluid bed and van Buijtenen et al. [31, 32] investigated the effect of elevating the spout on the dynamics of a (multiple) spout-fluidized bed. In the work by Fries et al. [26], an example of the RTD in the spray zone of a Wurster coater was reported by means of DEM-CFD 3 simulations. In addition, Yang et al. [29, 33, 34] presented the hydrodynamics in a 3D spouted bed and found that the solid residence time is shortest in the spout region. The aim of the present study is to establish and validate a DEM-CFD model for simulations of particle motion in a Wurster fluid bed. This is performed as an important step in developing a simulation tool for the entire particle coating process. By following particle trajectories, the CTDs and RTDs in different regions of the Wurster fluid bed process are determined and compared to data from recent PEPT experiments [17]. In these recent experiments, it was pointed out that it is difficult to detect the tracer particle in the spray region towards the bottom of the bed because the ο§-rays tend to be absorbed by the bulky metal parts in this region. Since it was not possible to employ the PEPT technique to measure the particle residence time in the spray zone, special attention is in the present study paid to evaluate the predicted particle motion in the spray zone. The validated DEM-CFD model is thus employed to simulate particle motion in the spray zone to gain an improved understanding of the coating process. These latter simulations are used to predict the residence time in the spray zone and to examine whether particles of one size may preferentially shield particles of a different size from the spray droplets. Lastly, the results are discussed in the context of coating and the effect on the overall coating process. 2. Mathematical model 2.1. Equations of particle motion The motion of an individual particle is described using Newtonβs second law ππ,π πππ,π ππ,π =π½ (ππ β ππ,π ) + ππ,π π β ππ,π π»π + ππ,π ππ‘ ππ (1) where ππ,π is the mass of the π π‘β particle, ππ,π is the particle velocity, ππ is the gas velocity, π is the gravitational acceleration, ππ,π is the particle volume, π»π is the gas pressure gradient, ππ is the particle volume fraction, ππ,π is the contact force during particle-particle and particle-wall collisions and π½ is the interphase momentum transfer coefficient. The particle volume fraction is calculated using π ππ = β π=1 ππ,π ππ (2) where ππ is the volume of the computational cell. The coupling between the discrete and continuous phase is handled based upon a multigrid technique [35], as described by e.g. 4 Bruchmüller et al. [36]. The particles are tracked on a so-called particle mesh, which is a Cartesian mesh with the size larger than the particle. All the coupling terms, including the volume fraction and the drag forces, are determined on the length-scale of this particle mesh. In case the local fluid cell is smaller than a particle, the coupling between that fluid cell and a particle occupying that fluid cell will be length-scale weighted and thus remain physical. The procedure has been described and tested by Mallouppas and van Wachem [37], and has been further worked out in the recent work of Capecelatro and Desjardins [38]. The interphase momentum transfer coefficient is based on the Ergun equation [39] in the dense regime and on the Wen and Yu drag correlation in the dilute regime [40], ππ ππ 2 + 1.75ππ π ππ ) 2 (150 ππ ππ π½= ππ ππ β2.65 3 π ππ πΆπ· 2 ππ ππ { 4 ππ > 0.2 ππ β€ 0.2 (3) where ππ = 1 β ππ is the gas volume fraction, ππ is the dynamic viscosity of air, and ππ is the particle diameter. In equation (3), πΆπ· is the drag coefficient, which is written as 1 + 0.15π ππ 0.687 ) π ππ < 1000 πΆπ· = { π ππ 0.44 π ππ β₯ 1000 24 ( (4) where π ππ is the particle Reynolds number π ππ = ππ ππ |ππ β ππ,π | ππ ππ (5) In equation (5) ππ is the air density. The angular momentum of the particle is calculated by πΌπ,π πππ,π = β π»π,π ππ‘ (6) where πΌπ,π is the moment of inertia of the particle, ππ,π is the rotational velocity and π»π,π is the total torque acting on the particle. 2.2. Soft sphere model In general, particle-particle and particle-wall collisions can be modeled using the hard sphere or soft sphere model. In the hard sphere model, the interaction forces are assumed to be impulsive and all other forces are negligible during collisions [41]. In the soft sphere model, the deformation of particles in contact is modeled by relating the 5 local linear deformation in the normal and tangential directions to a force in these directions, using Hertz-Mindlin theory [42]. The hard sphere model is easier to use but applicable only to binary collisions. The soft sphere model directly implements the physics of collisions but is computationally costly. In this study, since there are dense regions where many particles can be in contact for a long time, the soft sphere model is used. In the soft sphere model, deformation of particles is replaced with overlap of two particles and the energy loss during collisions is taken into account through a springdashpot system. This system is characterized using the spring stiffness, π, the damping coefficient, π , and the friction coefficient, π. The former two quantities are calculated using Hertz contact theory [42, 43], as explained below. The normal and tangential contact forces acting on the particle, πππ,ππ and πππ,ππ, are given by 3/2 πππ,ππ = βππ πΏπ πππ β πππ (πππ β πππ )πππ πππ,ππ = { (7) βππ‘ πΉπ‘ β ππ‘π πππ ππ |πππ,ππ | β€ π|πππ,ππ | βπ|πππ,ππ |πππ ππ |πππ‘,ππ | > π|πππ,ππ | (8) where πΏπ and πΉπ are the normal and tangential displacements of the particle, πππ and πππ are unit vectors normal and tangential to the contact plane, respectively, πππ is the relative velocity between the π π‘β and π π‘β particles, and πππ is the slip velocity of the contact point. The normal and tangential stiffnesses, ππ and ππ‘ , are expressed by β1 4 1 β ππ2 1 β ππ2 ππ = ( + ) 3 πΈπ πΈπ 1 β ππ2 1 β ππ2 ππ‘ = 8 ( + ) π»π π»π β1 ππ + ππ ( ) ππ ππ ππ + ππ ( ) ππ ππ β1β2 (9) β1β2 1/2 πΏπ (10) where πΈ is the Youngβs modulus of the particle, π» is the shear modulus, π is the Poissonβs ratio and π is the radius. The suffixes π and π‘ denote the components in the normal and tangential directions, while the suffixes π and π denote the π π‘β particle and the π π‘β particle respectively. According to Tsuji et al. [20], the damping coefficients ππ and ππ‘ represent the viscoelastic dissipation of kinetic energy in the normal and tangential directions, respectively. These are given as 6 1/4 ππ = 2πΌ βππ β ππ πΏπ (11) ππ‘ = 2πΌ βππ β ππ‘ (12) where πΌ denotes a constant related to the coefficient of restitution [44], and ππ β represents the effective particle mass and is calculated by ππ β = ππ,π ππ,π . ππ,π + ππ,π (13) More detailed description of the model can be found in literature [19, 20, 30, 41]. 2.3. Equations of gas flow A characteristic time scale of the flow may be calculated based on the atomizer flow rate and the nozzle diameter. The Reynolds number thus calculated is approximately 104 and single-phase flow of air may therefore be expected to be turbulent. However, since the Stokes number of the particles is quite large, turbulence is not expected to have a direct influence on the particle trajectories. In addition, for dense gas-solid flows, such as the one in this study, the particle stress is expected to be much greater than the stress due to turbulence [45]. A turbulence model is therefore not used in the DEM-CFD model. The continuity and momentum equations for gas flow are then written as follows π (π π ) + π» β (ππ ππ ππ ) = 0 ππ‘ π π (14) π π (π π π ) + π» β (ππ ππ ππ ππ ) = βππ π»π β π» β (ππ ππ ) + ππ ππ π β β π½(ππ β ππ,π ) ππ‘ π π π π=1 (15) where ππ is the viscous stress tensor for incompressible flow, π π π = ππ (π»ππ + (π»ππ ) ) (16) 3. Experimental 3.1. The Wurster bed configuration The model of the fluid bed used in this study is based on the geometry of the Strea-1 fluid bed. The fluid bed is 380 mm high, with top and bottom diameters of 250 mm and 114 mm respectively. Detailed dimensions are given in the experimental paper [17]. The atomization air flow was supplied through a nozzle with a diameter of 5 mm located 3 mm above the bottom of the fluid bed. This nozzle was only a big circular inlet with no opening for any liquid suspensions. Even in this case, the nozzle air velocity is high, 7 e.g. 50 m/s. This nozzle was used in the experiments in anticipation of future computational work so as to avoid the numerical difficulties associated with simulating sonic air flow while at the same time maintaining a high velocity jet. The fluidization air flow passes through the bowl-shaped distributor, which consists of a central base and an outer annular region. While the central base of the distributor is fully open, the spray nozzle at the center implies that the region is also annular. The outer annulus region of the distributor has a number of orifices with a diameter of 3 mm, as illustrated in Figure 2. A wire mesh screen was put over the distributor to prevent particles from falling down below the distributor. Figure 2 A sketch of the bowl-shaped distributor: 1) nozzle, 2) solid, 3) fully-opened central base, and 4) outer annulus 3.2. PEPT data In this work, calculations using the DEM-CFD model are compared to recent PEPT experimental data [17]; no additional experiments are performed. In the PEPT measurement system, a radioisotope is incorporated into a tracer particle. As the tracer particle moves around in the vessel the radioisotope decays in beta-decay and releases back-to-back Ξ³-rays. These Ξ³-rays are detected via two large position sensitive detectors. After a sufficient number of Ξ³-rays are collected the location of the tracer particle can be found through three dimensional triangulation. More details about the technique and the algorithms used to determine the location have been reported by Parker et al. [4648]. 3.3. Material As a common material in the pharmaceutical industry, microcrystalline cellulose (MCC) spheres were employed in the PEPT experiments, as well as a model particulate material in the DEM-CFD simulations. The pellets that typically are used in practice have a diameter that ranges from 200 µm to 1 mm. However, smaller or larger particles, such as tablets, are also coated using the Wurster process. In order to limit the number of particles, the particle size of 1749 and 2665 µm, which is still relevant and applicable to product development, was selected. In the PEPT experiments, the particle size was measured using a QICPIC Particle Size Analysis (Sympatec GmbH), and the sphericity ranged from 0.85 to 0.95 (see [17] for a photograph of samples). 8 4. Numerical 4.1. Meshing To solve the equations of particle motion and gas flow, a fully coupled multi-phase flow solver, MultiFlow (www.multiflow.org) is employed. The model of the fluid bed is the same as in the PEPT experiments. Figure 3 shows the global mesh and close-ups of the surface mesh at the bowl-shaped distributor and nozzle. Approximately 65000 hexahedral cells are required based on a grid independence check via simulations of single phase gas flow. The computational mesh near the distributor and inside the Wurster tube is locally refined in order to properly capture the flow characteristics in this region. Figure 3 (a) The surface mesh of the fluid bed and (b) the close-up of the bowl-shaped distributor (from top view) 4.2. Boundary and initial conditions In the recent PEPT experiments, the flow rates of the atomization and fluidization air were measured separately using rotameters [17]. These measurements provide the global flow rates, but they do not give any information about the flow distribution at the distributor. In order to specify the flow distribution at the distributor, a single-phase CFD model including the air supply chamber, the distributor, the wire mesh screen, and the fluid bed was developed in Ansys Fluent. In this single-phase CFD model, the distributor was modeled with all its orifices, but the wire mesh screen was included as a region with a specified pressure loss (see e.g. [49]). The results obtained using this single-phase CFD model (not shown) show that the air flow passing through the central base of the distributor is in between 53% and 64% of the total fluidization air flow. In addition to this single phase CFD model, the particle velocity in the lower part of the bed is also used as an indication of the flow distribution at the distributor. Since the resolution of the PEPT measured particle trajectories towards the bottom of the bed is low, it is necessary to employ measurements higher up. The resolution of the PEPT measurements is estimated at several positions along the length of the Wurster tube and a location at the middle of the Wurster tube, 90 mm above the bottom, is selected in order to compare experimental data with calculated results. The boundary condition employed in the DEM-CFD simulation reflects a flow distribution where 55% of the fluidization flow enters normal to the boundary in the 9 central region and 45% enters normal to the boundary in the outer annulus region. Figure 4, which shows the average vertical particle velocity as a function of the radial coordinate, illustrates that the particle velocity calculated in the DEM-CFD simulation agrees with that measured in the PEPT experiment [17]. Figure 4 The average vertical particle velocity along the radial direction for case #1 (VMD 1749 µm, batch size 200 g, fluidization air flow rate 73.3 m 3/h and atomization air flow rate 3.50 m3/h). As already discussed, the atomizer flow is imposed as a velocity inlet normal to the boundary at the nozzle. The walls of the fluid bed and the Wurster tube are set to be noslip for the gas flow. The outlet of the domain is considered to be pressure outlet. At the start-up of the simulations, 200 g (between approximately 15000 and 270000 particles depending on the particle size) particles are put into the vessel at a certain height above the distributor and are allowed to settle down without any gas flow. After 2 s, when particles are at rest near the bottom of the equipment, the gas flow is turned on. 4.3. Cycle and residence time distributions For simplicity we define the start of a particle coating cycle when a particle enters into the spray zone from the horizontal transport region or the lower region in the Wurster tube. The particle coating cycle then ends when the particle reappears in the spray zone after having subsequently traveled through the Wurster tube, the fountain, downbed, and horizontal transport regions. When one particle coating cycle ends, the next one begins. The particle coating cycle time is thus defined to be the time it takes for a particle to complete one cycle. In the recent PEPT experiments [17], the bulk of the particulate material that was used in each process experiment contained only one single tracer particle. This tracer particle was then followed via PEPT monitoring for 1.5 hours and the cycle and residence time distributions were calculated from different cycles for the same tracer particle. In the present DEM-CFD simulations, on the other hand, the calculation of the cycle and residence times is based on data from many particles within a short period of time. For the pseudo-steady particle dynamics in this fluid bed, as long as one particle is followed the information obtained (such as the particle velocity or the cycle time distribution) is assumed to be representative of the motion of all particles in a short period. 10 This study does not include any liquid spray. However, it is nevertheless of interest to understand the particle motion near the spray nozzle. A spray zone is therefore defined as shown in Figure 5, which gives a schematic of the shape of the spray zone, i.e. a solid cone. This model is mainly conceptual and similar to the one in the work by Fries et al. [26]. The height of the spray zone, L, is assumed to be 45 mm, which corresponds to the height where the cone approaches the tube wall. The spray half-angle, ΞΈ, is assumed to be 30 degrees. In order to study the shielding effect of different size particles, an entrance distance into the spray zone is defined as the distance between the spray nozzle and the location where the particle enters the spray zone (see Figure 5). Figure 5 A schematic of the spray zone 4.4. Simulation time In order to estimate the required simulation time the cumulative cycle time distributions are plotted for different simulation times, as shown in Figure 6. It can be seen that the CTD is not sensitive to the simulation time provided that it is at least 25 s, and this simulation time is therefore chosen for purposes of studying particle cycles and the CTD. Similar plots were also made for the RTD in the spray zone and in the Wurster tube (not shown). It was found that 10 s is sufficient in order to obtain a reasonable compromise between the computational cost and the quality of the data in order to calculate the RTD in the spray zone and in the Wurster tube. Figure 6 The cumulative cycle time distributions for different simulation times (with the first 2 s discarded), for case #1 (VMD 1749 µm, batch size 200 g, fluidization air flow rate 73.3 m3/h and atomization air flow rate 3.50 m3/h). 4.5. Simulation parameters The parameters used in the simulations are presented in Table 1 and the operating conditions for each case are summarized in Table 2. For Run #1 the same conditions as the base case in the experimental study are used, and the results are used for evaluating the DEM-CFD model in detail. Runs #2 and 3 with larger batch sizes of 400 g and 600 g are used to further evaluate the model as well as to verify the interpretations made in the experiments. The effect of particle size is studied in Runs #4 and 5 by increasing or decreasing the particle size by approximately 0.8 mm. Lastly, the effect of mixtures with 11 different components is studied in Runs #6-8 by replacing 25%, 50% or 75% (by mass) of 1749 µm particles with 2665 µm particles. A typical simulation is run in parallel using 32 CPUs and takes 12 hours per second. Table 1 The numerical parameters used in the simulations [50-52]. Table 2 The operating conditions for each DEM-CFD simulation. 5. Results and discussion In this study the performance of the DEM-CFD model is evaluated by comparing the calculated results with the results from previous PEPT experiments for the base case and for different batch sizes. In addition, simulations for different particle sizes and mixtures of different particle sizes are performed with emphasis on evaluating the effect on the RTDs in the spray zone and in the Wurster tube. 5.1. Validation of the DEM-CFD model 5.1.1. The general particle movement for the base case Figure 7 shows the particle velocity field determined in the DEM-CFD simulation and in the PEPT experiment respectively. It is seen that the characteristic motion of the particles in the Wurster fluid bed is predicted quite well using the DEM-CFD model. The particles accelerate in the Wurster tube to reach a maximum velocity of approximately 3.0 m/s (this maximum value is difficult to observe in the figure due to an overlap of the particle trajectories), and then fall down through the downbed region. Figure 7 The particle velocity field at a vertical cross-section through the center of the bed (a) simulated using DEM-CFD and (b) measured using PEPT (VMD 1749 µm, batch size 200 g, fluidization air flow rate 73.3 m3/h and atomization air flow rate 3.50 m3/h). By following particle trajectories, the cycle time and the residence times in different regions can be obtained. In Figure 8, the CTD of particles in the DEM-CFD simulation is compared with the CTD determined in the PEPT experiment. Since the actual simulation time is 25 s (with the first two seconds discarded), only particle cycles shorter than 25 s are used for this comparison, both in the simulation and in the experiment. Since only 12 cycles that are shorter than 25 s are used for the comparison, the experimental values of the cycle time and the RSD in the cycle time may be slightly different from those presented in the previous experimental study [17] in which all cycles were included. Figure 8 shows good agreement in terms of both the shape of the distribution and the actual values. In the DEM-CFD simulation, the CTD has a larger percentage of short cycle times compared to the CTD in the PEPT experiments. This difference may be attributed to a greater weight factor of short cycles in the DEM-CFD simulation since the DEM-CFD model follows many particles for a short time whereas the PEPT experiment follows a single tracer particle for a long time. Figure 9 shows the mean residence times of particles in different regions and the mean fractions of the cycle time spent in different regions. The DEM-CFD simulation predicts that particles spend the longest time in the horizontal transport region, and that the residence time is considerably shorter in the Wurster tube and in the fountain and downbed regions. This result corresponds closely to the corresponding values measured in the PEPT experiment, especially in terms of the mean fractions of the cycle time spent in different regions. That is, particles spend 19% of cycle time in the Wurster tube, 5%, 4% and 73% of cycle time in the fountain, downbed and horizontal transport regions in both the DEM-CFD simulation and in the PEPT experiment. Figure 8 The cycle time distribution (for cycles shorter than 25 s) calculated in the DEMCFD simulation and measured in the PEPT experiment (VMD 1749 µm, batch size 200 g, fluidization air flow rate 73.3 m3/h and atomization air flow rate 3.50 m3/h). Figure 9 (a) The mean residence times in different regions and (b) the mean fractions of the cycle time spent in different regions for case #1 (VMD 1749 µm, batch size 200 g, fluidization air flow rate 73.3 m3/h and atomization air flow rate 3.50 m 3/h). 5.1.2. Effect of batch size In addition to the general particle movement for a batch size of 200 g, simulations of different batch sizes of 400 g and 600 g are also performed. It is clearly shown in Figure 10, which shows the time-averaged solids fraction at a vertical cross-section through the center of the bed for different batch sizes, that a higher fountain is obtained with an increase in the batch size. As reported earlier [17], this increase in the fountain height is due to a higher gas flow rate and, hence, a faster acceleration of particles in the Wurster tube. In the PEPT experiments, this effect was attributed to an increased resistance in the downbed region, which increased the air flow rate through the Wurster tube. Here it 13 is possible to verify this interpretation by noting that the dense region in the downbed region increases when the batch size increases. As a result, the air flow rate passing through the Wurster tube increases from 34.9 m3/h to 40.1 m3/h, and to 51.7 m3/h when the batch size increases from 200 g to 400 g, and to 600 g respectively. It is also of interest to examine the effect of the batch size on the cycle time. In addition, the relative standard deviation (RSD) in the cycle time is calculated, since a variability in the cycle time can affect the quality of the product. Figure 11 shows the effect of batch size on the cycle time as well as on the RSD in the cycle time. There is good agreement between the measured and calculated mean cycle time. The measured and calculated values of the RSD do not agree so well, which could be due to the fact that spherical particles are assumed and the VMD of particles is employed in the simulations rather than the actual particle size distribution. But there is good agreement in the trend of a decreased RSD when increasing the batch size, except for the very slight increase in the RSD determined experimentally (from 63 to 66%) when the batch size increases from 200 to 400 g. This slight increase in the experimental RSD is different from the values of the RSD calculated based on all cycles, i.e. 77 and 76% for 200 and 400 g respectively [17]. Since only particle cycles shorter than 25 s are used for the comparison in Figure 11, the RSD in the cycle time is smaller than the RSD presented in the earlier study. Apart from the simulated RSD values, good agreement between the DEM-CFD simulations and the PEPT experiments is obtained for the cycle times, residence times and the trend of RSD. In the next sections it is therefore of interest to focus on the simulation results for different particle sizes and mixtures of different particle sizes. Figure 10 The solids fraction at a vertical cross-section through the center of the bed for different batch sizes: a) 200 g, b) 400 g and c) 600 g (VMD 1749 µm, fluidization air flow rate 73.3 m3/h and atomization air flow rate 3.50 m3/h). Figure 11 The mean cycle time and RSD for different batch sizes (VMD 1749 µm, fluidization air flow rate 73.3 m3/h and atomization air flow rate 3.50 m3/h). 5.2. Simulating with the DEM-CFD model 5.2.1. Effect of particle size Figure 12 shows that there is a significant effect of the particle size on the residence times in the spray zone and in the Wurster tube. When the particle size increases from 1000 µm to 2665 µm, there is an almost seven-fold increase in the residence times in the 14 spray zone, from 0.032 s to 0.214 s. For the same increase in the particle size, the increase in the residence time in the Wurster tube increases by a factor of almost 4, from 0.36 s to 1.38 s. These results indicate that large particles reside longer in the spray zone than small particles. If all particles of the same size in the spray zone receive the same amount of coating per unit time, large particles will then obviously receive more coating per unit area per pass than small particles. Fortunately, as large particles stay longer in the Wurster tube, they will also have a greater chance of drying as they move upwards through the Wurster tube. Figure 13 shows the RTDs in the spray zone for different size particles. Figure 13 shows that small particles have a narrow RTD in the spray zone while the RTD becomes much wider for large particles. This difference can be attributed to different terminal velocities for different size particles. For the same fluidization air flow rate, large particles are more likely to recirculate in the Wurster tube [17] and return to the spray zone than small particles. This effect can result in a wider distribution in the coating thickness. Figure 12 The simulated residence times in the spray zone and in the Wurster tube for different size particles. Figure 13 particles. The simulated residence time distributions in the spray zone for different size 5.2.2. Effect of mixtures of different size particles Figure 14 shows the mean residence times in the spray zone and in the Wurster tube for small and large particles in mixtures with different fractions of small and large particles. These 200 g mixtures of 1749 µm and 2665 µm particles contain 25%, 50% and 75% 2665 µm particles. It is seen that large particles stay longer both in the spray zone and in the Wurster tube. A longer residence in the spray zone can lead to more coating being deposited on the particle surface. Moreover, as shown in Figure 15, the large particles enter the spray zone closer to the spray nozzle than the small particles. This latter effect occurs because a greater gas velocity is required to accelerate the large particles. The large particles therefore have to move closer to the nozzle, where the gas velocity is higher, to be able to move upwards through the Wurster tube. The smaller entrance distance into the spray zone for the 15 large particles can result in the large particles shielding the small particles from the spray droplets. This effect [53], in addition to the effect of a longer residence time in the spray zone, suggests that the large particles receive more coating solution per cycle than the small particles. This was experimentally observed by Wesdyk et al. [54] for beads with a size distribution in the no. 14-20 mesh range. 5.2.3. Effect on coating thickness Based upon the simulation results above, the effect of the residence time in the spray zone, the entrance distance into the spray zone, the cycle time and the particle diameter on the coating thickness may be explored in terms of a simple model. In order to develop such a model, it is noted that the total amount of coating per unit time deposited on the surface of a particle, πππππ , can be expected to be proportional to the spray rate, πΜ, the time spent in the spray zone, π‘π ππππ¦ , and the number of coating cycles, πππ¦πππ . In addition, the probability that a spray droplet is deposited onto a particle can be expected to be proportional to the cross-sectional area of the particle and to the droplet flux, which decreases quadratically with the distance from the spray nozzle for a solid-cone spray zone. This simple model may thus be written ππππππ π‘π ππππ¦ πππ 2 β4 = πΎ(ππππ‘πππππ )πΜ ( )( ) ππ‘ π‘ππ¦πππ ππππ‘πππππ 2 (17) where π‘ππ¦πππ ~1/πππ¦πππ is the cycle time, which is available in Li et al. [17], and πΎ represents other factors that may affect the amount of coating solution that the particle receives such as the shielding effect. Since the shielding effect is predominantly entrance distance dependent, πΎ should be a function of the entrance distance, i.e. πΎ~1/ππππ‘πππππ . The rate of increase in the coating thickness can then be written ππππππ ππππππ 1 = ππ‘ πππππ πππ 2 ππ‘ (18) where πππππ is the density of the coating film. Using equations (17) and (18), the relative rate of increase of the coating thickness between the large and small particles for different mixtures can be explored in a postprocessing step, as illustrated in Figure 16. Figure 16 shows that the large particles only have a slightly larger increase in the coating thickness than the small particles when the fraction of large particles in the mixture is 25%. In this mixture the mean cycle times for the small particles and the large particles are 4.95 s and 7.94 s respectively [17], which indicates that the small particles pass through the spray zone 1.64 times more 16 frequently than the large particles. On the other hand, the large particles stay 1.48 times longer in the spray zone and move 1.06 times closer to the spray nozzle than the small particles. As a result, the increase in the residence time in the spray zone of the large particles is almost compensated for by the decrease in the number of passes through the spray zone. The end result in this particular case is that the large particles grow only slightly faster than the small particles. As the fraction of large particles in the mixtures increases from 25%, however, the difference in the cycle time between small and large particles decreases while the difference in the residence time in the spray zone increases. For these latter mixtures, the large particles therefore have a greater rate of increase in the coating thickness than the small particles. Figure 14 The simulated residence times of small and large particles in (a) the spray zone and in (b) the Wurster tube for different mixtures of small and large particles. Figure 15 The simulated entrance distance into the spray zone of small and large particles for different mixtures of small and large particles. Figure 16 The simulated relative rate of increase of the coating thickness between the large and small particles for different mixtures of small and large particles. 6. Conclusions In this study, coupled DEM-CFD simulations have been performed to study particle motion in a Wurster fluid bed. The particle trajectories were used to identify particle cycles and to determine the CTDs and RTDs of particles in different regions. The DEM-CFD model was validated by comparing the particle velocity field as well as cycle and residence time distributions with results from recent PEPT experiments. The general characteristic particle motion was successfully captured and the residence times of particles in different regions were found to correspond closely to the experimental results. A shorter cycle time with a larger batch size was also predicted by the DEM-CFD simulations, in agreement with the PEPT monitored experiments. The effect of particle size and mixtures of different size particles were studied in the DEM-CFD simulations. The results show that large particles spend a longer time in both the spray zone and the Wurster tube, suggesting that large particles get greater amount of coating solution per cycle compared to small particles. This difference is however, 17 partly compensated for by the fact that large particles pass through the spray zone less frequently than small particles due to their longer cycle times. The DEM-CFD simulations also show that the large particles on average enter the spray zone closer to the spray nozzle than the small particles. This indicates that the large particles can shield the small particles from the spray droplets, and that the large particles therefore receive a greater amount of coating solution per pass than what would be anticipated based on their larger size, and the longer time spent in the spray zone. A simple conceptual model was developed to predict the effect of the residence time in the spray zone, the cycle time, and the entrance distance on the relative rate of increase of the film thickness between large and small particles. This model showed that as the fraction of the large particles in the mixture increases, they have a greater rate of increase in the coating thickness than the small particles. Due to its simplicity, however, this model should be further developed in the future. Acknowledgements This work is undertaken within the EU seventh framework program, the PowTech Marie Curie Initial Training Network (Project no. EU FP7-PEOPLE-2010-ITN-264722). The experiments were financially supported by AstraZeneca R&D. Dr. Andy Ingram at University of Birmingham is gratefully acknowledged for the cooperation in the experimental work. The authors would also thank the high performance computing (HPC) team at AstraZeneca R&D for their support throughout the simulations. Notation 18 πΆπ· drag coefficient ππ particle diameter, m πΈ Youngβs modulus, Pa ππ contact force, N π gravity vector, m/s2 π» shear modulus, Pa ππ mass of the particle, kg π normal unit vector π tangential unit vector π°π moment of inertia, kgβm2 π pressure, N/m2 π ππ particle Reynolds number π‘ time, s π velocity vector of gas phase, m/s ππ velocity vector of the particle, m/s ππ volume of the particle, m3 ππ rotational velocity of the particle, rad/s Greek symbols ππ gas volume fraction ππ particle volume fraction π½ interphase momentum transfer coefficient, kg/(m3βs) ππ dynamic viscosity, Paβs π friction coefficient of particles π density, kg/m3 π damping coefficient π Poisson ratio 19 π viscous stress tensor, N/m2 Subscripts π the gas phase π the particle π, π the π π‘β or π π‘β particle π the normal direction π the tangential direction References [1] D.E. Wurster, Air-suspension technique of coating drug particles. A preliminary report, J. Am. Pharm. Assoc. (Wash). 48 (1959) 451-454. [2] E. Teunou, D. Poncelet, Batch and continuous fluid bed coating β review and state of the art, J. Food Eng., 53 (2002) 325-340. [3] K. Jono, H. Ichikawa, M. Miyamoto, Y. Fukumori, A review of particulate design for pharmaceutical powders and their production by spouted bed coating, Powder Technol., 113 (2000) 269-277. [4] R. Chopra, G. Alderborn, J.M. Newton, F. Podczeck, The influence of film coating on pellet properties, Pharm. Dev. Technol., 7 (2002) 59-68. [5] D. Ström, S. Karlsson, S. Folestad, I. Niklasson Björn, T. Laurell, J. Nilsson, A. Rasmuson, A new device for coating single particles under controlled conditions, Chem. Eng. Sci., 60 (2005) 46474653. [6] M. LuΕ‘trik, R. Dreu, S. SΕiΔ, Comparison and development of particle coating devices, Primerjava in razvoj naprav za oblaganje delcev, 61 (2010) 155-161. [7] F.N. Christensen, P. Bertelsen, Qualitative description of the Wurster-based fluid-bed coating process, Drug Dev. Ind. Pharm., 23 (1997) 451-463. [8] S. Karlsson, A. Rasmuson, I.N. Björn, S. Schantz, Characterization and mathematical modelling of single fluidised particle coating, Powder Technol., 207 (2011) 245-256. [9] S. Karlsson, I. Niklasson Björn, S. Folestad, A. Rasmuson, Measurement of the particle movement in the fountain region of a Wurster type bed, Powder Technol., 165 (2006) 22-29. [10] U. Mann, Analysis of spouted-bed coating and granulation. 1. Batch operation, Ind. Eng. Chem. Proc. DD., 22 (1983) 288-292. 20 [11] X.X. Cheng, R. Turton, The prediction of variability occurring in fluidized bed coating equipment. I. The measurement of particle circulation rates in a bottom-spray fluidized bed coater, Pharm. Dev. Technol., 5 (2000) 311-322. [12] S. Shelukar, J. Ho, J. Zega, E. Roland, N. Yeh, D. Quiram, A. Nole, A. Katdare, S. Reynolds, Identification and characterization of factors controlling tablet coating uniformity in a Wurster coating process, Powder Technol., 110 (2000) 29-36. [13] R. Turton, Challenges in the modeling and prediction of coating of pharmaceutical dosage forms, Powder Technol., 181 (2008) 186-194. [14] V. Mann, E. Crosby, Cycle time distribution measurements in spouted beds, Can. J. Chem. Eng., 53 (1975) 579-581. [15] M.J. San José, S. Alvarez, F.J. Peñas, I. García, Cycle time in draft tube conical spouted bed dryer for sludge from paper industry, Chem. Eng. Sci., 100 (2013) 413-420. [16] X.X. Cheng, R. Turton, The Prediction of Variability Occurring in Fluidized Bed Coating Equipment. II. The Role of Nonuniform Particle Coverage as Particles Pass Through the Spray Zonemr, Pharm. Dev. Technol., 5 (2000) 323-332. [17] L. Li, A. Rasmuson, A. Ingram, M. Johansson, J. Remmelgas, C. von Corswant, S. Folestad, PEPT study of particle cycle and residence time distributions in a Wurster fluid bed, AlChE J., 61 (2015) 756-768. [18] D. Jajcevic, E. Siegmann, C. Radeke, J.G. Khinast, Large-scale CFDβDEM simulations of fluidized granular systems, Chem. Eng. Sci., 98 (2013) 298-310. [19] P.A. Cundall, O.D. Strack, A discrete numerical model for granular assemblies, Geotechnique, 29 (1979) 47-65. [20] Y. Tsuji, T. Kawaguchi, T. Tanaka, Discrete particle simulation of two-dimensional fluidized bed, Powder Technol., 77 (1993) 79β87. [21] M.A. van der Hoef, M. van Sint Annaland, N.G. Deen, J.A.M. Kuipers, Numerical simulation of dense gas-solid fluidized beds: A multiscale modeling strategy, Annual Review of Fluid Mechanics, 2008, pp. 47-70. [22] J.M. Link, N.G. Deen, J.A.M. Kuipers, X. Fan, A. Ingram, D.J. Parker, J. Wood, J.P.K. Seville, PEPT and discrete particle simulation study of spout-fluid bed regimes, AlChE J., 54 (2008) 1189-1202. [23] H.P. Zhu, Z.Y. Zhou, R.Y. Yang, A.B. Yu, Discrete particle simulation of particulate systems: A review of major applications and findings, Chem. Eng. Sci., 63 (2008) 5728-5770. [24] W.R. Ketterhagen, M.T. Am Ende, B.C. Hancock, Process modeling in the pharmaceutical industry using the discrete element method, J. Pharm. Sci., 98 (2009) 442-470. [25] R. Turton, The application of modeling techniques to film-coating processes, Drug Dev. Ind. Pharm., 36 (2010) 143-151. [26] L. Fries, S. Antonyuk, S. Heinrich, S. Palzer, DEMβCFD modeling of a fluidized bed spray granulator, Chem. Eng. Sci., 66 (2011) 2340-2355. [27] P. Darabi, K. Pougatch, M. Salcudean, D. Grecov, DEM investigations of fluidized beds in the presence of liquid coating, Powder Technol., 214 (2011) 365-374. [28] L. Fries, S. Antonyuk, S. Heinrich, D. Dopfer, S. Palzer, Collision dynamics in fluidised bed granulators: A DEM-CFD study, Chem. Eng. Sci., 86 (2013) 108-123. 21 [29] S. Yang, K. Luo, M. Fang, J. Fan, Discrete element simulation of the hydrodynamics in a 3D spouted bed: Influence of tube configuration, Powder Technol., 243 (2013) 85-95. [30] N.G. Deen, M.V. Annaland, M.A. Van der Hoef, J.A.M. Kuipers, Review of discrete particle modeling of fluidized beds, Chem. Eng. Sci., 62 (2007) 28-44. [31] M.S. van Buijtenen, W.-J. van Dijk, N.G. Deen, J.A.M. Kuipers, T. Leadbeater, D.J. Parker, Numerical and experimental study on multiple-spout fluidized beds, Chem. Eng. Sci., 66 (2011) 2368-2376. [32] M.S. van Buijtenen, K. Buist, N.G. Deen, J.A.M. Kuipers, T. Leadbeater, D.J. Parker, Numerical and experimental study on spout elevation in spout-fluidized beds, AlChE J., 58 (2012) 25242535. [33] S. Yang, K. Luo, M. Fang, J. Fan, K. Cen, Influences of operating parameters on the hydrodynamics of a 3-D spoutβfluid bed based on DEM modeling approach, Chem. Eng. J., 247 (2014) 161-173. [34] S. Yang, K. Luo, J. Fan, K. Cen, Particle-scale investigation of the solid dispersion and residence properties in a 3-D spout-fluid bed, AlChE J., 60 (2014) 2788-2804. [35] J. Bruchmuller, S. Gu, K.H. Luo, B.G.M. Van Wachem, DISCRETE ELEMENT METHOD FOR MULTISCALE MODELING, Journal of Multiscale Modelling, 02 (2010) 147-162. [36] J. Bruchmuller, Modelling the degradation of particles in fluidised beds, Engineering Sciences, University of Southampton, PhD thesis, 2011, pp. 176. School of [37] G. Mallouppas, B. van Wachem, Large Eddy Simulations of turbulent particle-laden channel flow, Int. J. Multiphase Flow, 54 (2013) 65-75. [38] J. Capecelatro, O. Desjardins, An EulerβLagrange strategy for simulating particle-laden flows, Journal of Computational Physics, 238 (2013) 1-31. [39] S. Ergun, Fluid flow through packed columns, Chem. Eng. Prog., 48 (1952) 89-94. [40] C. Wen, Y. Yu, Mechanics of Fluidization, Fluidization, Chemical Engineering Progress Symposium Series 62, (1966) 100-111. [41] C.T. Crowe, J.D. Schwarzkopf, M. Sommerfeld, Y. Tsuji, Multiphase Flows with Droplets and Particles, Second Edition, CRC Press Inc, GB, 2012. [42] H. Hertz, {Über} die {B} erührung fester elastischer {K} örper, J. für die reine u. angew. Math., 92 (1882). [43] E. Dintwa, E. Tijskens, H. Ramon, On the accuracy of the Hertz model to describe the normal contact of soft elastic spheres, Granular Matter, 10 (2007) 209-221. [44] Y. Tsuji, T. Tanaka, T. Ishida, Lagrangian numerical simulation of plug flow of cohesionless particles in a horizontal pipe, Powder Technol., 71 (1992) 239-250. [45] C.M. Hrenya, J.L. Sinclair, Effects of particle-phase turbulence in gas-solid flows, AlChE J., 43 (1997) 853-869. [46] D.J. Parker, C.J. Broadbent, P. Fowles, M.R. Hawkesworth, P. McNeil, Positron emission particle tracking - a technique for studying flow within engineering equipment, Nucl. Instrum. Methods Phys. Res., Sect. A, 326 (1993) 592-607. 22 [47] D.J. Parker, D.A. Allen, D.M. Benton, P. Fowles, P.A. McNeil, M. Tan, T.D. Beynon, Developments in particle tracking using the Birmingham Positron Camera, Nucl. Instrum. Methods Phys. Res., Sect. A, 392 (1997) 421-426. [48] D.J. Parker, R.N. Forster, P. Fowles, P.S. Takhar, Positron emission particle tracking using the new Birmingham positron camera, Nucl. Instrum. Methods Phys. Res., Sect. A, 477 (2002) 540545. [49] D.W. Green, R.H. Perry, Perry's Chemical Engineers' Handbook (8th Edition), McGrawHill2008. [50] R. Roberts, R. Rowe, P. York, The Poisson's ratio of microcrystalline cellulose, Int. J. Pharm., 105 (1994) 177-180. [51] R. Bharadwaj, C. Smith, B.C. Hancock, The coefficient of restitution of some pharmaceutical tablets/compacts, Int. J. Pharm., 402 (2010) 50-56. [52] A. Darelius, E. Lennartsson, A. Rasmuson, I. Niklasson Björn, S. Folestad, Measurement of the velocity field and frictional properties of wet masses in a high shear mixer, Chem. Eng. Sci., 62 (2007) 2366-2374. [53] X. Cheng, R. Turton, The Prediction of Variability Occurring in Fluidized Bed Coating Equipment. II. The Role of Nonuniform Particle Coverage as Particles Pass Through the Spray Zonemr, Pharm. Dev. Technol., 5 (2000) 323-332. [54] R. Wesdyk, Y.M. Joshi, N.B. Jain, K. Morris, A. Newman, The effect of size and mass on the film thickness of beads coated in fluidized bed equipment, Int. J. Pharm., 65 (1990) 69-76. 23
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