Process systems modelling and applications in granulation: A review

Granulation is one of the fundamental operations in particulate processing and has a very ancient history and widespread use. Much fundamental particle science has occurred in the last two decades to help understand the underlying phenomena. Yet, until recently the development of granulation systems was mostly based on popular practice. The use of process systems approaches to the integrated understanding of these operations is providing improved insight into the complex nature of the processes.Improved mathematical representations, new solution techniques and the application of the models to industrial processes are yielding better designs, improved optimisation and tighter control of these systems. The parallel development of advanced instrumentation and the use of inferential approaches provide real-time access to system parameters necessary for improvements in operation. The use of advanced models to help develop real-time plant diagnostic systems provides further evidence of the utility of process system approaches to granulation processes. This paper highlights some of those aspects of granulation.     

Analysis of the start-up process in continuous fluidized bed spray granulation by population balance modelling

A physics-based population balance model is constructed for continuous fluidized bed spray granulation with internal and external separations. A balance area around the granulator and around the separator is described, including all input and output particle and mass flows. A simplified growth and attrition model is developed for the diameter change of the particles in the granulator. The population balances facilitate the calculation of the particle size distributions changing over time in the fluidized bed and in the product flow. It is demonstrated that an unsteady start-up phase occurred in every case, which possibly leads to instability (oscillating behaviour). This may be regulated by controlling the overall nuclei balance.     

Model-based design and control of a continuous drum granulation process

This paper is concerned with enhanced process design and control of a multiple-input multiple-output (MIMO) granulation process. The work is based on a first-principles mechanistic three-dimensional population balance model (3D-PBM), which has been previously validated against experiments at the laboratory-scale for various operating conditions and formulations. The main objective of this study is via a novel process design, to control and operate the granulation process under more optimal conditions. Novelty of the work lies in the usage of the validated 3D-PBM to extract suitable multiple control-loop pairings from which an overall control loop performance is qualitatively and quantitatively assessed. Results show that for most existing granulation process configurations, enhanced control-loop performance is not achieved and as a result an alternative process design strategy is necessary. The proposed design demonstrates increased efficiency in the control and operation of the granulation process, which is required for further efficient control and operation of subsequent downstream processes.     

Identification of models for control of wet granulation

The modeling work in this paper provides insight on improved control and design (including measurement selection) of a granulation process. Two different control strategies (MPC and PID) are evaluated on an experimentally validated granulation model. This model is based on earlier work done at The University of Sheffield, UK and Organon, The Netherlands [C.F.W. Sanders, W. Oostra, A.D. Salman, M.J. Hounslow, Development of a predictive high-shear granulation model; experimental and modeling results, 7th World Congress of Chemical Engineering, Glasgow (2005), C11-002]. The granulation kinetics were measured in a 10 liter batch granulator with an experimental design that included four process variables. The aggregation rates were extracted with a Discretized Population Balance (DPB) model. Knowledge of the process kinetics was used to model a continuous (well mixed) granulator. The controller model for the Model Predictive Controller is a linearized state space model, derived from the nonlinear DPB model. It has the four process variables from the experimental design and a feed ratio as input variables. Since the DPB model describes the whole Granule Size Distribution (GSD), candidate sets of lumped output variables were evaluated. When measuring controller performance based on the full granule size distribution, it is shown that a PID controller can actually produce results that fluctuate more than the open-loop response. An MPC controller improves stability on both process outputs and the full granule size distribution. The work shows that measuring and controlling specific number based lumped outputs result in a more stable process than when mass based lumped outputs are used. The paper describes a general strategy of using lab scale batch experiments to design and control (small or large scale) continuous granulators. The continuous experiments in this paper are based on simulation, therefore future experimental validation will elucidate further the link between batch and continuous granulation.     

Fluidized bed spray granulation: Analysis of the system behaviour by means of dynamic flowsheet simulation

Nowadays, software tools for the flowsheet simulation of industrial processes are commonly used for design, simulation, balancing, troubleshooting and optimization purposes. Most of the tools are applicable to fluid processes only and cannot be effectively used for processes which involve solids.In this contribution we want to present the conceptual design of a new system applicable for the dynamic flowsheet simulation of complex solids processes. This system is developed as an enhancement to the existing simulation program.The novel software is able to simulate the unsteady behaviour of complex circuits of granulation processes. The transient behaviour during the start-up and changing of the process or material parameters can also be examined.As flowsheet examples, a typical spray granulation process with different schemes consisting of fluidized bed granulators, screens, mill and splitters was used. The mathematical model of the fluidized bed granulator is described by a one-dimensional population balance equation and coupled with heat and mass transfer and simple fluid dynamics.Received simulation results have shown that the proposed concept of the dynamic flowsheet simulation of granulation processes can be used effectively and has the potential to be generalized for other types of solids processes.     

Investigating the dynamic behaviour of fluidized bed spray granulation processes applying numerical simulation tools

Particulate processes involve different kinetic processes such as formation of nuclei, their subsequent growth and breakage. In addition, external product classification can play a significant role. A reliable prediction and thorough understanding of potential sources for instability is not only of scientific interest but also an important issue for better process design and process control.The application of these nonlinear dynamics is concerned with fluidized bed spray granulation. Self-sustained oscillations may rise in processes with external product classification.Therefore, focus of this work is on process stability which can be influenced by classifying, milling and recycling of particles and by the production of internal and external seeds.First a brief introduction to the model is given, that couples the particle population state with thermodynamic-, fluiddynamic- and granulation process for a unit with non-classifying product discharge and a screening and milling unit in the seed recycle and builds the core of the software package AVA^®FBSim^®, used for the experiments.     

A control oriented study on the numerical solution of the population balance equation for crystallization processes

The population balance equation provides a well established mathematical framework for dynamic modeling of numerous particulate processes. Numerical solution of the population balance equation is often complicated due to the occurrence of steep moving fronts and/or sharp discontinuities. This study aims to give a comprehensive analysis of the most widely used population balance solution methods, namely the method of characteristics, the finite volume methods and the finite element methods, in terms of the performance requirements essential for on-line control applications. The numerical techniques are used to solve the dynamic population balance equation of various test problems as well as industrial crystallization processes undergoing simultaneous nucleation and growth. The time-varying supersaturation profiles in the latter real-life case studies provide more realistic scenarios to identify the advantages and pitfalls of a particular numerical technique.The simulation results demonstrate that the method of characteristics gives the most accurate numerical predictions, whereas high computational burden limits its use for complex real crystallization processes. It is shown that the high order finite volume methods in combination with flux limiting functions are well capable of capturing sharp discontinuities and steep moving fronts at a reasonable computational cost, which facilitates their use for on-line control applications. The finite element methods, namely the orthogonal collocation and the Galerkin's techniques, on the other hand may severely suffer from numerical problems. This shortcoming, in addition to their complex implementation and low computational efficiency, makes the finite element methods less appealing for the intended application.     

Parameter estimation in a multidimensional granulation model

A new multidimensional model for wet granulation is presented, which includes particle coalescence, compaction, reaction, penetration, and breakage. In the model, particles are assumed to be spherical and consist of two kinds of solid, two kinds of liquid, and pore volume. The model is tested against experimental results (Simmons, Turton and Mort. Proceedings of Fifth World Congress on Particle Technology, paper 9d, 2006) from the granulation of sugar particles with different PEG based binders in a bench scale mixer, being carried out for different impeller speeds, binder compositions and process durations. The unknown rate constants for coalescence, compaction, reaction, and breakage were fitted to the experiments and the sensitivities of the mass of agglomerates were calculated with respect to these parameters. This is done by employing experimental design and a response surface technique. The simulations with the established set of parameters show that the model predicts the trends, not only in time, but also for crucial process conditions such as impeller speed and the binder composition. As such it is found that more viscous binder promotes the formation of porous particle ensembles. Furthermore, the statistics of the different events such as collisions, coalescence and breakage reveal for instance that successful coalescence events outnumber the breakage events by a factor of up to three for low impeller speeds.     

Modelling of comminution processes in Spex Mixer/Mill

It is well known that mathematical models which simulate comminution processes represent a useful tool in several fields of academic and industrial research, with particular emphasis on nano-material and pharmaceutical production. In the present work a mathematical model which is able to quantitatively describe comminution processes in a ball milling system (i.e., Spex-Mixer/Mill) has been developed. The proposed approach takes into account three different contributions: dynamics of the vial, dynamics of spheres motion and simulation of the comminution process. The vial dynamics has been modelled by taking advantage of an appropriate roto-translation matrix. Model results have been successfully compared with literature experimental data. The spheres motion within the Spex Mixer/Mill has been simulated using a 3D dynamic model based on classical mechanics as well as the so-called discrete element method, which is widely adopted to quantitatively describe multi-body collision behaviour. In particular, existing models of impact with dissipation as well as the classical Hertz impact theory have been taken into account. This part of the global model allows one to obtain, for different operating conditions, the impact specific energy and impact velocity as a function of time. The latter ones represent input parameters for the simulation of comminution processes that is performed through suitable population balances, where different breakage functions as well as appropriate breakage probabilities have been considered. Model results are reported in terms of granulometric distribution of powders within the mixer-mill as a function of time, minimal grain size obtainable and time needed to complete the comminution process for various operating conditions (i.e., mill frequency and charge ratio).     

Development of a predictive high-shear granulation model

Within the pharmaceutical industry, high-shear granulation processes are well known for the production of drug-loaded granules. Development of such granulation processes, however, is often still more an art than a science. With the use of population balances, it is possible to link granulation rates to granule properties. Previous work demonstrated that good agreement between experimental and simulated results can be achieved [Powder Technol. 130 (2003) 162]. This enabled the granulation rates to be defined by two model parameters: the critical binder volume fraction and the aggregation rate constant. The modelling framework presented in this paper forms the basis of the kinetic analysis of granulation experiments that may lead to the development of a modelling tool that cannot only be used to simulate but also predict high-shear granulation behaviour in real-life pharmaceutical processes.     

Particle population modeling in fluidized bed-spray granulation—analysis of the steady state and unsteady behavior

Owing to its intensive mass and heat transfer ratios and its coupling of the process stages of drying, shaping and homogenization as well as classification, continuous fluidized bed-spray granulation drying has gained acceptance as a thermal treatment process for granular solids. In this study, a balance of the particle populations is completed for a continuous fluidized bed-spray granulation with external classification. Thus, it ought to be possible to describe the particle size distributions changing over time in the fluidized bed and in the product flow [Powder Technol. 82 (1995) 37; H. Uhlemann, L. Mörl, Wirbelschicht-Sprühgranulation, Springer Verlag, 2000, ISBN 3-540-66985-X.].     

The kinetics of the granulation process: Right from the early stages

In this study, experimentation and modelling were carried out to understand the granulation process. This work assesses whether there is a significant difference in the aggregation rate of the wet granulation process between the very early stages and later stages of high shear granulation. Measurements of the size distribution and binder content from the beginning of the process, just after liquid binder addition, were carried out. A population balance model based on two different kernels, the Equi Kinetic Energy (EKE) kernel and two-dimensional population balance equations with a Size Independent (SI) kernel, was applied to the high shear granulation process. It was concluded that the population balance equations with SI kernel best described the aggregation in the high shear granulation process. The value of aggregation rate constant in the early stages is smaller than aggregation kernel in the later stages.     

Empirical to mechanistic modelling in high shear granulation

This paper gives an overview of the different models available for granulation in high shear mixers with a focus on applicability in the pharmaceutical industry. Three examples of applications are given. The examples indicate the potential of mechanistically based models for scale-up and the importance of understanding the dynamics of the granulation process. The first two examples show how the impeller torque can be modelled and predicted in the dry and wet mixing phases of the high shear granulation process, using a solid mechanics and a hierarchical multivariate model, respectively. In the third application the particle size distribution is modelled using population balances and it is shown how different operating conditions can be included in the coalescence kernel to describe the granule growth.     

Population balance modelling for a flow induced phase inversion based granulation in a two-dimensional rotating agglomerator

A novel two-dimensional rotating agglomerator was developed to carry out the flow induced phase inversion (FIPI) based granulation. The process in this agglomerator shows that a continuous paste flow (mixed with liquid binder and primary particles) is extruded into the interstice of two relatively rotating disks, as the paste becomes solidified due to the loss of heat to the disks, it is then broken into granules by the shearing force imposed by the rotating disk. Experimental measurements have shown that the size of these granules is enlarged along the positive radial direction of the disks. It is also found that these granules contain approximately the same quantity of binder in terms of its volume fraction. The paper thus proposes a population balance (PB) model to describe the growth of the granules by considering a size independent agglomeration kernel. The PB simulated results are found to be well capable of describing the change of the particle size distribution (PSD) of the granules in the radial direction. This study also proposes a velocity profile for the paste flow and attempts to establish a quantitative relationship between the granulation rate and the deformation rate as this would help us understand the mechanism of the agglomeration. It is hoped that this study would be used to improve the design of the agglomerator and to assure the control of the process and the granular product quality.     

Studies of fluid bed granulation in an industrial R&D context

Following a brief overview of recent developments in laundry powder processing by comparison with other areas of industrial application, and current drivers and trends, a review is presented of collaborative research between Unilever R&D and Sheffield University on fluidised bed granulation using melt binders.These fall apart into 4 areas:

1.

Contact zone studies;

2.

Growth similarity for non-ideal systems;

3.

Growth and breakage decoupled;

4.

Scale-up rules based on similarity of growth kinetics.

The emphasis of the paper is on the identification and relative quantification of the dominant mechanisms, which are found in the balance of fluxes of solids and binder, together with heat transfer and conduction, not so much binder viscosity. These mechanisms allow for the control of the growth kinetics and rapid scale-up.Together, this lays the broad ground-work for fluidised bed granulation. Some concluding remarks provide pointers for the future of research in this area:

•

There is a strong requirement for multi-dimensional phase volume distribution based population balances.

•

Many processes require pre-granulation, and liquid-liquid contact in the spray-zone is scarcely investigated.

•

Simple combined Lagrangian-Eulerian modelling implemented in commercial code environment can be especially useful to investigate the effects of the relations between material properties and process conditions on growth kinetics.

     

Identification of thermal zones and population balance modelling of fluidized bed spray granulation

Air temperature measurements in a fluidized bed of glass beads top sprayed with water showed that conditions for particles growth were fulfilled only in the cold wetting zone under the nozzle which size and shape depended on operating conditions (liquid spray rate, nozzle air pressure, air temperature, and particles load). Evolution of the particle size distribution during agglomeration was modelled using population balance and representing the fluidized bed as two perfectly mixed reactors exchanging particles with particle growth only in the one corresponding to the wetting zone. The model was applied to the agglomeration of non-soluble glass beads and soluble maltodextrin particles spraying respectively an acacia gum solution (binder) and water. Among the three adjustable parameters, identified from experimental particle size distributions evolution during glass beads agglomeration, only one describing the kinetics of the size distribution evolution depended on process variables. The model allowed satisfying simulation of the evolution of the particle size distribution during maltodextrin agglomeration.     

Spray-agglomeration of NPK-fertilizer in a rotating drum granulator

The continuous production of 3 to 4.5 mm NPK-granules is achieved by spraying an appropriate mixture onto recycle or reflux (undersize) product in a rotating drum. Hot air is used to evaporate the water. An extensive study was performed on an industrial granulator to evaluate mass and energy balances, to define the average residence time of the reflux-particles and to develop a model for particle growth.The average residence time was measured from tracer experiments. The mechanism of granulation follows the particle growth principle of drying and layering. Model equations developed by Nienow for a batch fluidized bed granulation were modified to predict continuous operations.The model equation defines the thickness of the coating layer in terms of the initial particle size and mass flow rate of the reflux particles, the mass flow rate of the sprayed mixture, and both the average residence time of the particles and their contact time with the spray. The resulting equation is

     

A basic population balance model for fluid bed spray granulation

A basic population balance approach is developed for a granulation process in a fluid bed spray granulator. The particle size distribution predicted by the model is confirmed by plant data. Hence this model is considered to be useful to describe and optimize an industrial process. The model depends on a limited number of parameters (most of these factors can be measured or are known): the spray volume flux, the nucleation fraction (the fraction of the spray volume flux which leads to new particles formed), the nucleation particle diameter, the product withdrawal threshold diameter, and the product withdrawal rate. Analysis of the model reveals a steady-state constraint; a steady state does not exist if the nucleation fraction is too large. For cases where the steady state does exist, the steady-state particle size distribution is solved analytically. A numerical implementation of the model is used to illustrate the transient evolution of the process. The steady-state solution appears to be stable for a constant nucleation fraction. However, if the nucleation fraction depends on the bed height the steady state can be unstable. Such a situation may occur if the spray inlet is near the height of the bed surface. Instead of convergence towards a steady state, the transient solution displays ongoing oscillatory behavior with an oscillation period of a number of hours. A linear stability analysis is performed to confirm the findings on the stability of the steady state.     

A three-dimensional population balance model of granulation with a mechanistic representation of the nucleation and aggregation phenomena

A comprehensive model is discussed for wet granulation based on a three-dimensional population balance, as an attempt to capture particle-level phenomena and their influence on the population-level behaviour. The three dimensions of population distribution are the particle size, binder content, and porosity of the granules. In formulating the population balance, these three particle traits are represented in terms of three equivalent traits, namely, the solid volume, liquid volume and gas volume of the granules. The model accounts for wetting, nucleation, aggregation and consolidation phenomena. Mechanistic kernels are derived for aggregation and nucleation, employing theories on these particle-level microscale phenomena that have already been validated in previous studies. The three-dimensional population balance is solved numerically using a finite volume-based decomposition algorithm also called the hierarchical two-tier solution strategy [Pinto, M.A., Immanuel, C.D., Doyle III, F.J., 2007. A feasible solution technique for higher-dimensional population balance models. Computers and Chemical Engineering, 31, 1242-1256].     

A volume-based multi-dimensional population balance approach for modelling high shear granulation

A volume-based multi-dimensional population balance model based on the approach used by Verkoeijen et al. [2002. Population balances for particulate processes—a volume approach. Chemical Engineering Science 57, 2287-2303], is further developed and applied to a wet granulation process of pharmaceutically relevant material, performed in a high shear mixer. The model is improved by a generalization that accounts for initial non-uniformly distributed liquid and air among the different particle size classes. Only the wet massing period of the granulation process has been modelled and it is experimentally found that the pores in the granules are fully saturated by liquid, i.e., no air is present in the granules during this period. Hence, an alternative model formulation is used as no model for the air in the granules is needed. Particle volume distribution, liquid saturation, liquid-to-solid ratio and porosity of the granules can all be modelled, as these properties can all be expressed as combinations of three model parameters, i.e., the volume fraction of solid material, total liquid fraction and the liquid fraction inside the granules. The model is also improved by introducing a new coalescence kernel and by increasing the number of size classes used. The simulated results are compared to measurements from a series of five designed experiments where impeller speed and water content are varied. It is found that the evolution of the volume, liquid saturation and porosity distributions could all be explained by fitting the compaction and coalescence rate constants.