Nucleation, growth and breakage phenomena in agitated wet granulation processes: a review

Wet agglomeration processes have traditionally been considered an empirical art, with great difficulties in predicting and explaining observed behaviour. Industry has faced a range of problems including large recycle ratios, poor product quality control, surging and even the total failure of scale up from laboratory to full scale production. However, in recent years there has been a rapid advancement in our understanding of the fundamental processes that control granulation behaviour and product properties. This review critically evaluates the current understanding of the three key areas of wet granulation processes: wetting and nucleation, consolidation and growth, and breakage and attrition. Particular emphasis is placed on the fact that there now exist theoretical models which predict or explain the majority of experimentally observed behaviour. Provided that the correct material properties and operating parameters are known, it is now possible to make useful predictions about how a material will granulate. The challenge that now faces us is to transfer these theoretical developments into industrial practice. Standard, reliable methods need to be developed to measure the formulation properties that control granulation behaviour, such as contact angle and dynamic yield strength. There also needs to be a better understanding of the flow patterns, mixing behaviour and impact velocities in different types of granulation equipment. (C) 2001 Elsevier Science B.V. All rights reserved.

Scaleup of wet granulation processes: science not art

Significant advances have been made in the last decade to quantify the process of wet granulation. The attributes of product granules from the granulation process are controlled by a combination of three groups of processes occurring in the granulator: (1) wetting and nucleation, (2) growth and consolidation and (3) breakage and attrition. For the first two of these processes, the key controlling dimensionless groups are defined and regime maps are presented and validated with data from tumbling and mixer granulators. Granulation is an example of particle design. For quantitative analysis, both careful characterisation of the feed formulation and knowledge of operating parameters are required. A key thesis of this paper is that the design, scaleup and operation of granulation processes can now be considered as quantitative engineering rather than a black art. Résumé

Modelling nucleation in wet granulation

Nucleation is the first stage in any granulation process where binder liquid first comes into contact with the powder. This paper investigates the nucleation process where binder liquid is added to a fine powder with a spray nozzle. The dimensionless spray flux approach of Hapgood et al. (Powder Technol. 141 (2004) 20) is extended to account for nonuniform spray patterns and allow for overlap of nuclei granules rather than spray drops. A dimensionless nuclei distribution function which describes the effects of the design and operating parameters of the nucleation process (binder spray characteristics, the nucleation area ratio between droplets and nuclei and the powder bed velocity) on the fractional surface area coverage of nuclei on a moving powder bed is developed. From this starting point, a Monte Carlo nucleation model that simulates full nuclei size distributions as a function of the design and operating parameters that were implemented in the dimensionless nuclei distribution function is developed. The nucleation model was then used to investigate the effects of the design and operating parameters on the formed nuclei size distributions and to correlate these effects to changes of the dimensionless nuclei distribution function. Model simulations also showed that it is possible to predict nuclei size distributions beyond the drop controlled nucleation regime in Hapgood's nucleation regime map. Qualitative comparison of model simulations and experimental nucleation data showed similar shapes of the nuclei size distributions. In its current form, the nucleation model can replace the nucleation term in one-dimensional population balance models describing wet granulation processes. Implementation of more sophisticated nucleation kinetics can make the model applicable to multi-dimensional population balance models.

A compartmental CFD-PBM model of high shear wet granulation

The conventional, geometrically lumped description of the physical processes inside a high shear granulator is not reliable for process design and scale-up. In this study, a compartmental Population Balance Model (PBM) with spatial dependence is developed and validated in two lab-scale high shear granulation processes using a 1.9L MiPro granulator and 4L DIOSNA granulator. The compartmental structure is built using a heuristic approach based on computational fluid dynamics (CFD) analysis, which includes the overall flow pattern, velocity and solids concentration. The constant volume Monte Carlo approach is implemented to solve the multi-compartment population balance equations. Different spatial dependent mechanisms are included in the compartmental PBM to describe granule growth. It is concluded that for both cases (low and high liquid content), the adjustment of parameters (e.g. layering, coalescence and breakage rate) can provide a quantitative prediction of the granulation process.

Dimensionless spray flux in wet granulation: Monte-Carlo simulations and experimental validation

Dimensionless spray flux Ψa is a dimensionless group that characterises the three most important variables in liquid dispersion: flowrate, drop size and powder flux through the spray zone. In this paper, the Poisson distribution was used to generate analytical solutions for the proportion of nuclei formed from single drops (fsingle) and the fraction of the powder surface covered by drops (fcovered) as a function of Ψa. Monte-Carlo simulations were performed to simulate the spray zone and investigate how Ψa, fsingle and fcovered are related. The Monte-Carlo data was an excellent match with analytical solutions of fcovered and fsingle as a function of Ψa. At low Ψa, the proportion of the surface covered by drops (fcovered) was equal to Ψa. As Ψa increases, drop overlap becomes more dominant and the powder surface coverage levels off. The proportion of nuclei formed from single drops (fsingle) falls exponentially with increasing Ψa. In the ranges covered, these results were independent of drop size, number of drops, drop size distribution (mono-sized, bimodal and trimodal distributions), and the uniformity of the spray. Experimental data of nuclei size distributions as a function of spray flux were fitted to the analytical solution for fsingle by defining a cutsize for single drop nuclei. The fitted cutsizes followed the spray drop sizes suggesting that the method is robust and that the cutsize does indicate the transition size between single drop and agglomerate nuclei. This demonstrates that the nuclei distribution is determined by the dimensionless spray flux and the fraction of drop controlled nuclei can be calculated analytically in advance.

Liquid distribution in wet granulation: dimensionless spray flux

This study investigates binder distribution in wet granulation and focuses on the nucleation zone, which is the area where the liquid binder and powder surface come into contact and form the initial nuclei. An equipment independent parameter, dimensionless spray flux Psi (a), is defined to characterise the most important process parameters in the nucleation process: solution flowrate, powder flux, and binder drop size. Ex-granulator experiments are used to study the relationship between dimensionless spray flux, process variables and the coverage of binder fluid on the powder surface. Lactose monohydrate powder on a variable speed riffler passed under a flat spray once only. Water and 7% HPC solution at two spray pressures were used as binders. Experiments with red dye and image analysis demonstrate that changes in dimensionless spray flux correlate with a measurable difference in powder surface coverage. Nucleation experiments show that spray flux controls the size and shape of the nuclei size distribution. At low Psi (a), the system operates in the drop controlled regime, where one drop forms one nucleus and the nuclei size distribution is narrow. At higher Psi (a), the powder surface cakes creating a broader size distribution. For controlled nucleation with the narrowest possible size distribution, it is recommended that the dimensionless spray flux be less than 0.1 to be in the drop-controlled regime. (C) 2001 Elsevier Science S.A. All rights reserved.

Control of fluidized bed spray granulation processes

Magdeburg, Univ., Fak. für Elektrotechnik und Informationstechnik, Diss., 2012

Model-based measurement and control of fluidised bed spray granulation processes

Magdeburg, Univ., Fak. für Verfahrens- und Systemtechnik, Diss., 2012

Optimal control and operation of drum granulation processes

Process optimisation and optimal control of batch and continuous drum granulation processes are studied in this paper. The main focus of the current research has been: (i) construction of optimisation and control relevant, population balance models through the incorporation of moisture content, drum rotation rate and bed depth into the coalescence kernels; (ii) investigation of optimal operational conditions using constrained optimisation techniques; (iii) development of optimal control algorithms based on discretized population balance equations; and (iv) comprehensive simulation studies on optimal control of both batch and continuous granulation processes. The objective of steady state optimisation is to minimise the recycle rate with minimum cost for continuous processes. It has been identified that the drum rotation-rate, bed depth (material charge), and moisture content of solids are practical decision (design) parameters for system optimisation. The objective for the optimal control of batch granulation processes is to maximize the mass of product-sized particles with minimum time and binder consumption. The objective for the optimal control of the continuous process is to drive the process from one steady state to another in a minimum time with minimum binder consumption, which is also known as the state-driving problem. It has been known for some time that the binder spray-rate is the most effective control (manipulative) variable. Although other possible manipulative variables, such as feed flow-rate and additional powder flow-rate have been investigated in the complete research project, only the single input problem with the binder spray rate as the manipulative variable is addressed in the paper to demonstrate the methodology. It can be shown from simulation results that the proposed models are suitable for control and optimisation studies, and the optimisation algorithms connected with either steady state or dynamic models are successful for the determination of optimal operational conditions and dynamic trajectories with good convergence properties. (c) 2005 Elsevier Ltd. All rights reserved.

Selection of operational parameters for the production of instant soy protein isolate by pulsed fluid bed agglomeration

The objective of this study was to select the optimal operational conditions for the production of instant soy protein isolate (SPI) by pulsed fluid bed agglomeration. The spray-dried SPI was characterized as being a cohesive powder, presenting cracks and channeling formation during its fluidization (Geldart type A). The process was carried out in a pulsed fluid bed, and aqueous maltodextrin solution was used as liquid binder. Air pulsation, at a frequency of 600 rpm, was used to fluidize the cohesive SPI particles and to allow agglomeration to occur. Seventeen tests were performed according to a central composite design. Independent variables were (i) feed flow rate (0.5-3.5 g/min), (ii) atomizing air pressure (0.5-1.5 bar) and (iii) binder concentration (10-50%). Mean particle diameter, process yield and product moisture were analyzed as responses. Surface response analysis led to the selection of optimal operational parameters, following which larger granules with low moisture content and high process yield were produced. Product transformations were also evaluated by the analysis of size distribution, flowability, cohesiveness and wettability. When compared to raw material, agglomerated particles were more porous and had a more irregular shape, presenting a wetting time decrease, free-flow improvement and cohesiveness reduction. (C) 2010 Elsevier B.V. All rights reserved.

Nucleation regime map for liquid bound granules

Nucleation is the first step in granulation where the powder and liquid first contact. Two types of nucleation in wet granulation processes are proposed. Drop controlled nucleation, where one drop forms one nucleus, occurs when drops hitting the powder surface do not overlap (low spray flux Psi(a)) and the drop must wet quickly into the bed (short drop penetration time t(p)). If either criterion is not met, powder mixing characteristics will dominate (mechanical dispersion regime). Granulation experiments were performed with lactose powder, water, PEG200, and 7% HPC solution in a 6 L and a 25 L mixer granulator. Size distributions were measured as the drop penetration time and spray flux were varied. At short penetration times, decreasing Psi(a) caused the nuclei distribution to become narrower. When drop penetration time was high, the nuclei size distribution was broad independent of changes in dimensionless spray flux. Nucleation regime maps were plotted for each set of experiments in each mixer as a function of the dimensionless distribution width delta. The nucleation regime map demonstrates the interaction between drop penetration time and spray flux in nucleation. The narrowest distribution consistently occurred at low spray flux and low penetration time, proving the existence of the drop controlled regime. The nucleation regime map provides a rational basis for design and scale-up of nucleation and wetting in wet granulation.