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Particle formation in fluidized beds is widely applied in an industrial context for the solidification of liquids and size enlargement of granular materials. The two main size-enlargement mechanisms are layering growth and agglomeration. For continuous process configurations with sieve-mill-recycle and layering growth only, the occurrence of undesired self-sustained oscillations in the particle size distribution under certain process conditions is well-known. This contribution investigates the stability of the practically relevant process with additional particle agglomeration by means of a model-based numerical bifurcation analysis. It is shown that the occurrence of stable limit cycles is inhibited by an increased rate of particle agglomeration for a variety of different process conditions and different agglomeration kinetics. These results enhance the understanding of the agglomeration and layering growth dynamics and are relevant for the process design and operation. [ABSTRACT FROM AUTHOR]

Spherical agglomeration technology can produce high‐performance spherical particles in a single crystallization unit, although it is still challenging to control the particle size and shape. To solve this issue, a two‐step bridging (TSB) mechanism containing a preconditioning period, size period, and shape period is proposed. The dynamic balance among the forces of adhesion, dispersion, and capillary action in the multi‐liquid phases plays a key role. This is fully considered to establish the TSB‐based thermodynamic size model and particle design framework by weighting the force action regions in multi‐liquid phases with dynamic composition. The spherical agglomerates of benzoic acid, celecoxib, and salicylic acid with narrow particle size distributions and tunable particle size ranges of 2000–5000, 800–3500, and 1500–4500 μm, respectively, were designed and prepared successfully, showing good correlation with the calculation, which is superior to the reported methods and indicates that the mechanism has certain universality and guiding significance. [ABSTRACT FROM AUTHOR]

Spherical agglomeration (SA) is a process intensification strategy, which can reduce the number of unit operations in pharmaceutical manufacturing. SA merges drug substance crystallization with drug product wet granulation, reducing capital, and operating costs. However, SA is a highly nonlinear process, thus for its efficient operation model‐based design and control strategies are beneficial. These require the development of a high‐fidelity process model with appropriately estimated parameters. There are two major problems associated with the development of a high‐fidelity process models—(i) selection of the appropriate model corresponding to the underlying process mechanisms, and (ii) accurate estimation of the parameters. This work focuses on the identification of the best fitting model that correlates with experimental observations using cross‐validation experiments. Further, an iterative model‐based experimental design strategy is developed, which uses D‐optimal experimental design criterion to minimize the number of experiments necessary to obtain accurate parameter estimates. [ABSTRACT FROM AUTHOR]

One of the key challenges that the pharmaceutical industry is trying to address is to maintain particle properties across the entire purification and isolation process. This research focuses on the effect of slurry properties, wash solvent, filtration and washing mechanisms on API agglomeration/granulation during the processes of downstream isolation and the impact on the physical properties of the product. In this investigation, each isolation step was analysed to identify factors that have the potential to affect the final product qualities using a multivariate statistical design of experiments approach. The factors which were most detrimental in increasing particle agglomeration, were found to be the particle size of the input material, the quantity and identity of wash solvent and the drying mode. Low boiling point aliphatic hydrocarbons are shown to be desirable final wash solvents to reduce the extent and strength of agglomerates and to produce free flowing powder/readily disrupted agglomerates. Unlabelled Image • Filtration, washing and drying parameters impact the isolated product quality. • Particle size, agglomeration extent and mechanical properties are affected. • Guidance is provided on API isolation strategy to minimize agglomeration. • The effect of sedimentation prior to filtration was investigated. • 1H NMR used to monitor cake washing efficiency. [ABSTRACT FROM AUTHOR]

Acetaminophen is a well‐known medicine frequently used as analgesic in fever treatment. In pharmaceutical formulation procedure, batch fluidized bed wet granulation is a bottleneck process for the continuous processing of acetaminophen from powder to solid dosage form. To meet the market demand and reduce operating costs, fluid bed wet granulation needs process intensification by converting batch to continuous process. For the scale‐up and batch to continuous conversion procedure, investigation on acetaminophen agglomeration kinetics is necessary. Therefore, this work investigates agglomeration kinetics of acetaminophen through batch fluidized bed wet granulation experiments, and the kinetic parameters are estimated using inverse modeling. Experiments are conducted on a 5‐L capacity pilot scale batch fluidized bed granulator. The effects of various process parameters, namely, binder concentration, spray rate, atomization pressure, and batch size, on particle size distribution are investigated. A 1‐D population balance model with Equi‐Kinetic Energy kernel for agglomeration is simulated to compare with the experimental data. The mean particle diameter increased when binder spray rate and binder concentration are increased and that the mean particle diameter decreased with increase in the atomization pressure and batch size. Experiments data comparison with the model can be used for process intensification with reasonable accuracy. [ABSTRACT FROM AUTHOR]

Effects of ascorbic acid and sodium sulfite on texture of cooked aged rice were researched in this study. Hardness increase and stickiness reduction are common for cooked aged rice. The texture of cooked aged rice was significantly changed approaching to fresh rice by both reducing agents despite of sulfur-containing or not (p < 0.05), and the values of hardness, stickiness and stickiness/hardness ratio could be completely restored to the levels of the corresponding fresh rice. Moreover, this effect showed a dose-effect relationship. Morphology examination suggested that ascorbic acid made starch granules swelling adequately and full of larger dents in the interior of cooked aged rice, while sodium sulfite only made starch granules displayed relatively smaller dents. Particle size analysis indicated that ascorbic acid enhanced the swelling and separation of starch granules, but sodium sulfite only promoted the granule separation due to deagglomeration. Therefore, the two reducing agents are useful in restoring texture of aged rice to fresh rice through changing gelatinization behavior and can be as a key probe to disclose aging mechanisms of rice. Unlabelled Image • Ascorbic acid and sodium sulfite restored the fresh texture of cooked aged rice. • Sodium sulfite enhanced the separation of starch granules during gelatinization. • Ascorbic acid promoted the swelling and separation of gelatinized starch granules. • Rice aging is closely related to the separation of gelatinized starch granules. [ABSTRACT FROM AUTHOR]

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Graphical abstract Abstract Roller compaction is the main technique employed in dry granulation. Ribbon sticking and splitting are among the major factors that can hinder the use of this process for some formulations. Ribbon splitting can occur either transversally (through the ribbon thickness) or longitudinally (through the ribbon width). It was observed that transverse splitting is commonly associated with sticking of the split ribbons to the rollers and results in an inferior performance of the process. Longitudinal splitting is associated with an across-width distribution of the ribbon density so that there may an adverse effect on the mechanical strength and dissolution properties of the tablets formed from the milled granules. The aim of the current work was to elucidate the mechanisms of splitting by an experimental study involving single component powders with a range of yield strengths, including those that are commonly used as excipients. Both smooth and knurled rollers were employed without and with lubrication by applying magnesium stearate to the rollers. The minimum gap was fixed and the maximum roll stress was varied. The observed trends for the smooth rollers were rationalised in terms of a splitting index, which is a measure of the residual stresses driving crack growth relative to the tensile strength of the ribbons. There was a lower limit at which splitting was observed but the occurrence of transverse splitting decreased and that for longitudinal splitting increased with increasing values of the index, which was accompanied by an increase in mixed transverse-longitudinal splitting. Transverse splitting was always associated with sticking to the rollers and was prevented by external lubrication. The main difference with the knurled rollers was that in some cases transverse splitting occurred without sticking to the rollers. A detailed discussion of the mechanisms involved is presented. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The effect of thermal binders on the physicochemical properties of gabapentin, a thermally labile drug, in granules prepared using twin-screw melt granulation was investigated in this study. Hydroxypropyl cellulose (HPC), a thermoplastic high molecular-weight binder, was compared against conventional low molecular-weight semi-crystalline thermal binders PEG 8000 and Compritol. Both the chemical degradation and polymorph form change of gabapentin were analyzed. The effects of particle size and molecular weight of HPC on the properties of granules were also studied. To overcome the high melt viscosity of HPC, higher barrel temperatures and higher specific mechanical energy were required to attain suitable granules. As a result, higher levels of gabapentin degradant were observed in HPC-based formulations. However, gabapentin form change was not observed in all formulations. Smaller particle size and lower molecular weight of HPC led to faster granule growth. The tabletability of granules was insensitive to the variations in particle size and molecular weight of HPC. Gabapentin crystal size reduction, HPC size reduction, and HPC enrichment on granule surface were observed for HPC-based granules. [ABSTRACT FROM AUTHOR]

Abstract In recent years, sustainable management of construction waste has garnered increasing attention. However, most previous studies mainly focused on turning construction wastes into recycled aggregates, whereas, recycling of those construction wastes below 5 mm has often been challenged or ignored. This study attempted to effectively deal with such recycled fine powders by employment of granulation technology to produce artificial aggregates with a diameter of 5–20 mm. The optimal granulation parameters were identified through a systematic experimental test. Moreover, the effect of water and cement content, as well as curing regimes, on the properties (such as shape and strength) of the prepared artificial aggregates was also investigated. More importantly, influence of normal curing and CO 2 curing on the strength development of artificial aggregates was examined and compared. In doing so, the scheme of preparation of artificial aggregates with optimal strength was developed. Findings from this study provide an alternative and viable solution to effectively dealing with construction wastes in an environmentally-friendly way and serve as a reference for follow-up studies in the future. Meanwhile, the carbonated artificial aggregate can be potentially used to replace natural aggregates in the preparation of low-strength concrete and blocks. [ABSTRACT FROM AUTHOR]

The particles with a narrow size distribution are proper products in a fluid bed granulation and coating. As well, the process efficiency is one of the most important parameters, and the wall deposition of sprayed liquid reduces it. The modality of spray volume distribution is a key parameter in the definition of particle size distribution and process efficiency. This work is done in two steps: In the first step, an experimental study on spray characteristics including spray flux distribution, spray cone angle, and discharge coefficient is conducted. Based on the experimental data, the curves of liquid volume flux versus nozzle pressure and height are obtained. The results indicate that the flux distribution changes significantly with even small pressure and height changes. In the second step, the granulation process is carried out in a semi-industrial conical fluid bed, and the particles size distribution curves and the deposited mass on the bed wall are obtained. The results show that the precise determination of the spray flux distribution is an appropriate way to predict the well-advised nozzle pressure/height in order to achieve the narrow particle size distribution and high efficiency of the process. [ABSTRACT FROM AUTHOR]

Abstract: For the production of particles in fluidized beds with a monodisperse grain band spectrum usually sift‐grind cycles are used. The agglomeration phenomena occurring in this process, the disintegration, the abrasion, the overspray and the dust binding, are usually not considered individually. The aim of this research work is to determine the dependence of specific process parameters on a special fluidized bed granulation process with self‐nucleation in order to make it more controllable. For a more detailed description of this process, a simplified mathematical model is presented in this paper. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Wetting condition of particle–wall collisions influence collision dynamics. • Higher energy dissipation for wet particle than for wet wall. • Additional energy dissipation possibly due to liquid inertia. • Wet–wet collision superposition of effects of wet particle and wet wall. Abstract Particulate processes are characterised by intense contacts between particles and particles with the apparatus walls, where often liquid is present on the surfaces in form of droplets or liquid layers, e.g. in granulation and agglomeration processes. However, the influence of the liquid on collision dynamics is still not fully understood. Therefore, the influence of the liquid on wet particle–wall collisions is investigated via the coefficient of restitution (CoR). The CoR characterises the total energy dissipation during a collision and is defined as ratio of rebound velocity to impact velocity. In most literature regarding collision dynamics of wet particles, a target plate is covered by a liquid layer before the collision. However, this approach is often questioned of its similarity to real wet particle collisions. Therefore, during this work the particle was wetted before colliding with a dry or wet plate. Normal CoR was higher for a wet plate than for a wet particle. The case of a wet–wet collision is comparable to a superposition of collisions where a wet particle or a wet plate was used. Furthermore, during oblique collisions the tangential CoR was found to be smaller for a wet wall compared to a wet particle impacting on a dry wall. [ABSTRACT FROM AUTHOR]

This study describes a novel approach for the use of thermal analysis to study the aftermath of the fluid bed melt granulation process and to depict the growth mechanism of the granules by quantifying the enthalpies of the granules at every physicochemical change using DSC and their mass loss through TG coupled to MS for a qualitative determination of the composition and amount of the evolved gases for the corresponding fragment ion. The experiments were made in situ with lactose monohydrate and two viscosity grades of PEG (2000 and 6000) as meltable binders with different contents and size fractions. DSC showed the presence of a beta lactose endotherm peak after the melting of alpha lactose and a proportional increase in its intensity with the increase in the particle size and the content of the binder, which suggested a relation with the agglomeration growth. Interestingly, TG and MS showed a larger reduction in the water content from lactose with the increase in the binder particle size, making it possible to evaluate the dehydration during the melt granulation. Indeed, during the distribution mechanism the low binder particle size and viscosity exposed lactose to a high heat transfer from the fluidizing air. However, a high binder particle size results in lactose immersed in the PEG particles, causing water to be trapped inside the granules and hence a larger reduction in water mass loss indicating the immersion mechanism. Therefore, thermal analysis is a promising tool for granulation growth control. [ABSTRACT FROM AUTHOR]

The objective of this study was to improve the disintegration and dissolution characteristics of a highly water-soluble tablet matrix by altering the manufacturing process. A high disintegration time along with high dependence of the disintegration time on tablet hardness was observed for a high drug loading (70% w/w) API when formulated using a high-shear wet granulation (HSWG) process. Keeping the formulation composition mostly constant, a fluid-bed granulation (FBG) process was explored as an alternate granulation method using a 2(4−1) fractional factorial design with two center points. FBG batches (10 batches) were manufactured using varying disingtegrant amount, spray rate, inlet temperature (T) and atomization air pressure. The resultant final blend particle size was affected significantly by spray rate (p = .0009), inlet T (p = .0062), atomization air pressure (p = .0134) and the interaction effect between inlet T*spray rate (p = .0241). The compactibility of the final blend was affected significantly by disintegrant amount (p < .0001), atomization air pressure (p = .0013) and spray rate (p = .05). It was observed that the fluid-bed batches gave significantly lower disintegration times than the HSWG batches, and mercury intrusion porosimetry data revealed that this was caused by the higher internal pore structure of tablets manufactured using the FBG batches. [ABSTRACT FROM AUTHOR]

The influence of a functionalized raw material particle structure on the granulation behavior and tabletabilty of calcium carbonate (CaCO 3 ) was investigated. Therefore, a milled grade of CaCO 3 was compared to different binary mixtures of milled and functionalized CaCO 3 . Relevant properties of raw materials, ribbons and granules were measured. The starting materials and two fractions of dry granules were compressed to tablets. The tabletability of granules was compared to that of the powders and the influence of specific compaction force and granule size on tablet tensile strength was evaluated. Adding functionalized particles drastically influenced the granulation and tableting behavior of CaCO 3 . Increasing proportions increased the ribbon porosity and granule size. Tensile strength of tablets from powder mixtures and granules was increased as well. Nevertheless, adding functionalized CaCO 3 led to a loss in tabletability induced by a previous compaction step to an extent depending on its proportion in the formulation. A clear influence of the particle morphology on granulation and tableting behavior was demonstrated by the study. The functionalized structure showed aspects of a more plastic deformation behavior. Adding functionalized CaCO 3 to a mixture, even in small amounts, seemed to be beneficial to increase granule size and tablet strength. [ABSTRACT FROM AUTHOR]

The aim of this work is to follow the agglomeration mechanism of an in situ Fluid Bed Melt Granulation (FBMG) by means of machine learning with Artificial Neural Network (ANN) modelling. Scanning Electron Microscopy (SEM) was used as a complementary tool with particle size analysis to evaluate the effect of the material properties on the quality attributes of the final granules and provide further insight into the growth mechanisms. The experiments were performed using lactose monohydrate as model filler and two grades of polyethylene glycol (PEG 2000 and 6000) as meltable binders in different contents and in different size fractions, respectively. A multilayer perceptron neural network was developed using MATLAB neural network toolbox and the evaluated quality attributes of the final granules were used as a database for the development and selection of the optimal architecture of the ANN model. The Garson equation was used to quantify the relative importance of each independent variable and thus it was established that the particle size had the highest impact on the granule properties. The distribution and immersion granule growth mechanisms were determined to occur for low and high binder particle size, respectively, as confirmed by the SEM pictures, and the response surfaces helped determine the optimal design space of the process and the optimal FBMG conditions. [ABSTRACT FROM AUTHOR]

Highlights • A model of autoagglomeration under mechanical vibration is derived. • The existence of an equilibrium granule size is predicted. • The model predictions are compared with experiments from literature. • Equilibrium granule size reached as a result of the balance between breakage and densification. • A maximum granule size with vibration intensity is predicted. Abstract Fine particles in the micron size range or smaller are usually so cohesive that they cannot exist as individual entities and are in cluster form, the size of which depends on the stress history. During handling, transportation or storage, the powder is subjected to mechanical vibration and/or agitation and, as a result of which clumping of particles or “snowballing” can occur even without the presence of any binder. This is an undesirable feature, as it is responsible for poor flow behaviour, cohesive arching, segregation of lumps and inducing flaws in products. Nevertheless, the mechanism of auto-agglomeration of cohesive powder has not received due attention and the conditions under which such clusters/lumps form, their size, structure and strength has not been analysed extensively. In this work we present a preliminary model to predict the equilibrium cluster size based on two separate energy balances to predict the granule solid fraction and equilibrium size, respectively. Despite some broad approximations, this approach can capture the trend of variation of the agglomerate size with the vibration intensity for some data reported in the literature. The proposed model also identifies the mechanism controlling the growth of the agglomerates as the balance between the cohesive energy of the particles and the disruptive energy of vibration. [ABSTRACT FROM AUTHOR]

Fluidized beds are widely used in pharmaceutical industry for particles coating and granulation. Due to the complex gas solids flow process, it is extremely desirable that a real time monitoring and control system is used in the process in order to enable a bubbling stable fluidization and reduce the chance of defluidization due to agglomeration with high moisture contents particles. The microwave tomography (MWT) technology has been developed for more than twenty years and was mainly applied in medical sectors. MWT has a wide range of frequency (1–2.5 GHz) and can be used to measure materials with high permittivity and conductivity. Therefore, it is a good choice for the monitoring of fluidized bed coating and granulation processes. In this paper, a MWT system with 16 antennas was designed and applied for the monitoring of wetting and coating processes in a lab-scale fluidized bed with top-spray and bottom-spray system. The hydrodynamics characteristics of wet gas-solids flow with different moisture content were investigated by MWT technology. This is the first time that MWT was applied in a real dynamics gas-solids fluidized bed. Experiment result shows that the MWT is available for the online monitoring of the gas solids flow with different moisture content. Different flow regimes were revealed based on the MWT images combined with pressure signals. The results indicate that the MWT provides valuable information to identify the defluidization in the fluidized bed process with high moisture contents materials. It is evident that microwave tomography has clear advantages over single point based measurement technology for process fault diagnose. [ABSTRACT FROM AUTHOR]

The granulation step determines the production yield and the final characteristics of the agglomerated couscous grains of durum wheat. The objective of the present work was to explore the capability of the fluidised bed technology to produce agglomerates of durum wheat semolina. The impacts of different processing conditions have been investigated on the structure and functional properties of the agglomerates. The size, shape, water content, compactness, and mechanical strength of the granules were measured. The fluidized bed agglomeration process has been found to produce agglomerates of durum wheat with different attributes compared to those produced by granulation using the low shear mixers. The results were discussed in regard to the hydro-textural approach, in order to get a better understanding of the mechanisms and relationships between process, structure, and properties. Two major agglomeration mechanisms contribute to the growth of the wet agglomerates: a fractal-structuring process followed by a phenomenon of densification. By studying the evolution of the compactness, diameter and water content, it was demonstrated that inter granular arrangements led to an expansion followed by a densification of the wet agglomerates. A relationship was proposed to describe the growth using a fluidized bed of the wet agglomerates of durum wheat semolina. [ABSTRACT FROM AUTHOR]

Understanding the growth mechanisms in granulation process is an important topic, providing valuable insights and supports control strategies. Typically, observations in high shear granulators are made after stopping the process. In this work, an in-process sampling technique is described and applied to a high shear wet granulation process. Different samples can be collected over the cause of the high shear granulation process. This allowed observation of the evolution of granules during addition of water at a constant flowrate. For a typical pharmaceutical formulation, we observed that granules nucleate in the first 2 min after starting the water addition and then grow to an average size of 200–1200 μm at 12.5 min, corresponding to a sharp increase in torque. Longer water addition times lead to oversized granules and eventually a paste and highly fluctuating torque. Sampling was also continued after stopping water addition which showed with time larger formed granules smoothen, whilst the smaller ones disintegrate. The work shows the in-process sampling can facilitate the identification of the granule growth kinetics and required binder quantity in high shear granulation. [ABSTRACT FROM AUTHOR]

In a fluidized bed spray granulation, a particle-particle adhesion by a liquid bridge, which shows dynamic motion due to moving particles, is the most fundamental phenomenon. Therefore, understanding of the particle-particle adhesion by such a dynamic liquid bridge is very important to elucidate mechanisms of particle agglomeration phenomenon in the wet granulation. In this study, the particle-particle adhesion phenomenon at the individual particle scale was analyzed using a direct numerical simulation. Collision of two particles mediated by binder droplets on a particle surface was simulated. In particular, the effect of droplet size under constant total liquid volume on adhesiveness of two colliding particles was investigated. In the present simulation, multiple liquid bridges were simultaneously formed, and these liquid bridges coalesced into single liquid bridge. The simulation results exhibited that the adhesiveness of particles increased with a decrease in the droplet diameter under a constant total liquid volume. In an initial stage of the particle growth in a fluidized bed spray granulation, the tendency of the calculations was consistent with experimental results. We revealed that the capillary pressure force and shapes of the liquid bridge are key factors for particle-particle adhesion at different droplet sizes under constant total liquid volume. [ABSTRACT FROM AUTHOR]

This work presents a systematic experimental study of continuous spray fluidized bed (SFB) layering granulation with external product separation. In layering granulation processes the product particle morphology is controlled by the drying conditions during operation. But varying drying conditions during continuous SFB layering granulation have a significant influence on process stability. High fluidizing gas inlet temperature, high fluidizing gas mass flow rate and low spray mass flow rate, resulting in intense drying conditions, led to stable steady state operation. An equilibrium between seed particle production, particle growth and product discharge was established. In contrast, low fluidizing gas inlet temperature, low fluidizing gas mass flow rate and high spray mass flow rates, resulting in moderate drying conditions, led to self-sustained oscillations of the particle size distribution (PSD) in the fluidized bed. The oscillations in PSD where partly transmitted to the PSD of the product, but they were limited by the mesh widths of the sieves, which were used for external separation. For the cases with an oscillatory steady state, equilibrium between seed particle formation, particle growth and product discharge could not be achieved due to temporarily excessive seed particle formation. [ABSTRACT FROM AUTHOR]

Discrete particles with the moisture in a rotating system tend to form themselves as lumped mass granules of different sizes. This paper depicts the agglomeration of the particles using batch and continuous system through the mathematical modeling. The liquid bridge formation, coalescence and breakage are essential steps in the agglomeration process of continuous system. The combination of two effects, namely, binder viscosity and surface tension will govern the bridge formation. In case of batch system of granulation, a regime map of granulation behaviour has been developed for the particulate system of sago powder-water mixer. This regime map predicts the granule growth behaviour and it is possible to assist in designing and controlling the granulation systems. In these processes, mass of the granules varies continuously with respect to time. According to the conditions of coalescence and breakage behaviour, the agglomeration is maximum during three to six minutes of granulation due to the maximum percentage of granule breakage. After six minutes the granule breakage and growth is gradually reduced and after 10 min there is no granule growth due to minimum or no breakage. The number of granule breakage increases with the Stokes deformation number. [ABSTRACT FROM AUTHOR]

The granulation of ammonium chloride (AC) fertilizer has been investigated in a laboratory scale based on the pan granulator at ambient temperature. Significant improvement of granulation efficiency of AC was achieved by using polyaluminium chloride (PAC) as solid binder and urea as granulation additive. Highly charged cations by PAC hydrolysis could reduce the electrostatic force of AC, resulting in efficient particle agglomeration. Analyzing the surface structure and characteristics of the PAC and AC granules revealed their interactions, which lead to the formation of aggregate nucleus. Furthermore, PAC contained a larger number of active groups, which served as bridges to form particle-polymer-particle complex, and facilitated the growth of particle. Meanwhile, urea and AC could react with each other to form stable inclusion complex which also had pronounced effect on the increase of granulation rate for AC. [ABSTRACT FROM AUTHOR]

The purpose of this study was to establish a relationship between the physical properties of powders and their behavior during high shear granulation. Hawthorn leaf extract was utilized as a model drug, and microcrystalline cellulose (MCC) and soluble starch were selected as excipients. The extract was mixed with each of the different excipients at ratios of 1:0.5, 1:1 and 1:2 by weight. The granules were prepared by high shear granulation (HSG). The wet granulated product was evaluated by monitoring responses such as the granule yield, the ratio of lumps to fine powder, the angle of repose of the granules (granule-AOR) and the Hausner ratio of the granules (granule-HR). The effect of the powder's physical properties on the granulation behavior was analyzed through stepwise regression. The critical relative humidity, particle size (d50), surface free energy, AOR, moisture content, equilibrium hygroscopic moisture content ( f), specific surface area, pore volume, Carr index, contact angle with water and bulk density were the main factors linked to the granule product. The main physical properties of the extract powder were the important factors in HSG. The findings from this study are useful in preparing ideal granulation products by reasonably controlling the physical properties of powders. Practical Applications The present work investigated the influence of the physical properties of Hawthorn leaf extract on high shear granulation behavior. Results showed that critical relative humidity, particle size, surface free energy, angle of repose, moisture content, equilibrium hygroscopic moisture content, specific surface area, pore volume, Carr index, contact angle with water and bulk density were the main factors linked to the granule product. Taking into consideration that the food industry uses Hawthorn leaf extract not only to plant health product as nutrient supplement but to botanical drug in several countries, this work is a useful guide to prepare ideal granulation products by reasonably controlling the physical properties of powders. [ABSTRACT FROM AUTHOR]

Particulate solids have received great interest in many industrial fields for both marketing reasons and technological aspects. In this study granular systems were achieved by using a wet granulation process using hydroxypropyl methylcellulose (HPMC) and distilled water as the binder phase. Particulates with a defined size (450–2000 μm) and good flowability together with a high granulation process yield, to reduce manufacturing scrap, were produced. To this aim a bench scale low-shear rate granulator apparatus was used; three process parameters were varied (impeller rotation speed, binder volume at constant mass, and binder flow rate) and, for each parameter, three intensities have been used. HPMC granule production was planned using the Central Composite Design (CCD) statistical protocol, which allowed us to minimize the number of runs to be performed for obtaining information about the relationship between granule properties and process parameters. The produced granules were stabilized by using a dedicated dynamic drying apparatus, then separated by sieving and then characterized in terms of size and flowability properties. The results of the experimental campaign have been used to develop semi-empirical correlations between granulated product properties and process parameters. A second-order polynomial law has shown the best comparison between experimental data and model predicted values. These correlations can constitute a reliable tool to help us to know more on the effect of operative parameter changes in HMPC or similar particulate solid production. [ABSTRACT FROM AUTHOR]

The results of theoretical and experimental investigations of particles agglomeration in a speed granulator accompanied by the break-up of particles have been presented. The dependences that make it possible to estimate the contribution of agglomeration and break-up during the formation of granules from powder particles and to determine the average weight of particle on the apparatus outlet have been proposed. [ABSTRACT FROM AUTHOR]

This paper presents a multi-compartment population balance model for wet granulation coupled with DEM (discrete element method) simulations. Methodologies are developed to extract relevant data from the DEM simulations to inform the population balance model. First, compartmental residence times are calculated for the population balance model from DEM. Then, a suitable collision kernel is chosen for the population balance model based on particle–particle collision frequencies extracted from DEM. It is found that the population balance model is able to predict the trends exhibited by the experimental size and porosity distributions by utilising the information provided by the DEM simulations. [ABSTRACT FROM AUTHOR]

This paper presents the results of research on improving the efficiency of the mechanical agglomeration through optimising the distance to which the ram approaches the die face in the final position. The focus of this study is the influence of the compression length on the value of the ultimate stress in the process of mechanical agglomeration of crystallized carbon dioxide. The first part of the paper proposes a model describing the influence of the geometric parameters of the residual amount of material which must remain in the cylinder on the value of axial force during subsequent compression phase of the process. The research part of the paper presents the empirical research results to verify the proposed model. The results of the work will be used to determine the influence of the described geometrical parameters of the dry ice residue on the axial force value. The derived mathematical model will be used for defining the design requirements as the starting point for the design and building of dry ice compression and granulation machines. [ABSTRACT FROM AUTHOR]

This research was conducted to cultivate granular sludge directly in a continuous-flow membrane bioreactor and explore the main factors influencing the granulation process. By establishing a suitable internal hydrodynamic circulation in a membrane bioreactor, granular sludge (GS) was successfully cultivated into mature granules with a compact structure and clear shape, in which extracellular polymeric substances played an important role in maintaining its integrity. The results showed that the main factors to determine the cultivation of GS included the total retention of sludge by the membrane module, the internal hydrodynamic circulation, and the entanglement of filamentous bacteria to sludge particles. Filamentous bacteria initiated a granulation process under the action of internal circulation, and maintained the stability of GS for a long period by wrapping biomass aggregates together. Even though filamentous bacteria were the major dominant microbial species in the bioreactor, the microbial community was richly biodiverse, and was responsible for the removal of organic pollutants and nutrients. Overall, the results demonstrated an alternative option for cultivating stable GS directly in a continuous-flow membrane bioreactor. [ABSTRACT FROM AUTHOR]

Context:The flow and compaction properties of a compaction mixture or powder and the drug-release profile of final tablets are important critical quality attributes (CQAs) that have an impact on the overall performance of hydrophilic matrix tablets. The selection of granulation method can importantly affect these CQAs. Objective:This study investigates various agglomeration methods of sustained-release formulation using HPMC K4M as a release polymer with various wet- and dry-granulation techniques. Materials and methods:Flow properties were determined using flow time, angle of response, and the Carr index. Compaction properties were evaluated using “out of die” Heckel model. Release of carvedilol was tested as 12-h drug-dissolution profile. Results and conclusion:Compression mixtures made using the wet-granulation method exhibit better flow and compression properties than compression mixtures made using the dry-granulation method. The direct compression method proved to be the least appropriate manufacturing method because the compression mixture has very poor flow and the lowest compressibility/compactibility index. The choice of granulation technique significantly influences the swelling behavior and drug-dissolution profile of the final matrix tablets, also resulting in dissimilar release profiles. The choice of granulation method has the greatest influence on the drug-release profile. The direct compression method provides tablets with the fastest drug-release profile, followed by the dry-granulation and wet-granulation methods. The particle size of granules and porosity of tablets play an important role, contributing to differences in drug-release profiles. [ABSTRACT FROM PUBLISHER]

Five reactors were operated with low upflow superficial air velocities (0.41 cm min −1 ) in order to observe granulation on synthetic wastewaters with different characteristics: 1) 340 mg-COD L −1 ; 2) 630 mg-COD L −1 ; and 3) 1300 mg-COD L −1 . Stable granulation was only observed under low hydrodynamic shear for low-strength wastewater. 55–70% of soluble chemical oxygen demand (COD) was utilized before aeration and 91% COD, 62% total nitrogen (TN), and 96% total phosphorus (TP) were removed from the low-strength wastewater. Although medium-strength wastewater did generate granules they rapidly acquired a filamentous surface layer that resulted in decreased performance and loss of nitrification. 94% COD, 30% TN, and 85% TP were removed from the medium-strength wastewater. The high-strength wastewater did not develop granules and 85% COD was removed. Results demonstrated that high shear force was not required for granulation. Rather, granulation depended on multiple parameters to out-select rapidly growing aerobic microorganisms. [ABSTRACT FROM AUTHOR]

A novel approach was developed for phosphorus recovery from wastewater through thermal treatment of matured phosphorus-accumulating granular sludge cultivated in sequencing batch airlift reactor (SBAR) system. Results showed that SBAR system had stable performances, in which COD, total phosphorus (TP) and total nitrogen (TN) removal efficiencies were stabilized at 80%, 89% and 86%, respectively. The matured granules were gathered from SBAR reactor and heated at relatively low temperature (100 °C, 200 °C, 300 °C). The total P content in thermal treated granular sludge was more than half of total nutrient. Furthermore, the phosphorus release rate for treated granules was negatively correlated with thermal treatment temperature. These results demonstrated that the granules harvested from SBAR system followed with thermal pre-treatment could probably be applied as excellent slow-release phosphorus fertilizer. Hence, low temperature treatment of phosphate-accumulating granules is efficient for phosphorus recovery from wastewater, which is likely to promote the application of granulation technology. [ABSTRACT FROM AUTHOR]

The effects of fluidised bed (FB) and high shear mixer (HS) granulation processes on water adsorption and flow properties of milk protein isolate powder (MPI) were investigated and compared. The agglomerated granules were characterised by different size fractions. It was found that granules produced from the HS process adsorbed less moisture, with slower adsorption kinetics, compared to those produced from using the FB. Granulation reduced the cohesiveness of the MPI powder, with HS having a significant greater impact due to the formation of the particles with higher bulk density and larger size. Particle size played a critical role that influenced water adsorption and flowability. Granulation processes contributed to different degrees to reducing the minimum outlet diameters of hoppers based on either mass-flow or core-flow discharges. HS granules had large wall friction angles, suggesting a need for steeper hopper walls for effective discharge. [ABSTRACT FROM AUTHOR]

Sintering is an agglomeration process that fuses iron ore fines, fluxes, recycled products, slag-forming elements and coke. The purpose of sintering is to obtain a product with suitable composition, quality and granulometry to be used as burden material in the blast furnace. This process is widely studied and researched in the iron and steelmaking industry. In this context, achieving an adequate sintered product depends on the adequate raw materials supply and the previous stage to the sintering process, granulation. For that reason, in this paper, the granulation process is studied as a consequence of being the source of pre-agglomerated materials for the subsequent sintering process. Thus, the main tests used to the determination of the properties are reviewed as well as the main granulation processes. [ABSTRACT FROM AUTHOR]

• Sound absorption behavior of granular aerogel layers strongly depends on particle size distribution. • Agglomerates with average particle sizes larger than 100 μm behave differently than those with smaller particle sizes. • Biot's limp porous media formulation accurately captures the response of granular aerogels larger than 100 μm. • A poro-elastic formulation is more suitable for modeling the low-frequency response of the smaller aerogel granules. We investigate the sound absorption characteristics of granular aerogel agglomerates of various particle sizes. The normal incidence sound absorption coefficients of six commercially available silica aerogels with different particle size distributions are measured using a two-microphone normal incidence impedance tube. The measurements show a strong correlation between the particle size and sound absorption behavior and reveal important differences between the sound absorption trends of granular aerogel particles larger than 100 μm and those smaller than 50 μm. These differences are further investigated using an inverse characterization method to extract the representative bulk properties necessary to model such agglomerates using the Johnson-Champoux-Allard formulation. Our results show that while agglomerates of larger aerogel granules can be modeled as limp porous media, smaller aerogel granules require a poro-elastic formulation. Further, we show that the inclusion of a logarithmically decreasing dynamic loss factor improves the low-frequency sound absorption predictions of the sub-50 μm aerogels. [ABSTRACT FROM AUTHOR]

This study is concerned with identifying the design space of two different continuous granulators and their respective granulation mechanisms. Performance of a continuous high shear granulator and a twin screw granulator with paracetamol formulations were examined by face-centered cubic design, which focused on investigating key performance metrics, namely, granule size, porosity, flowability and particle morphology of granules as a function of essential input process parameters (liquid content, throughput and rotation speed). Liquid and residence time distribution tests were also performed to gain insights into the liquid-powder mixing and flow behavior. The results indicated that continuous high shear granulation was more sensitive to process variation and produced spherical granules with monomodal size distribution and distinct internal structure and strength variation. Twin screw granulation with such a particular screw configuration showed narrower design space and granules were featured with multimodal size distribution, irregular shape, less detectible porosity difference and tighter range of strength. Granulation mechanisms explored on the basis of nucleation and growth regime maps revealed that for most cases liquid binder was uniformly distributed with fast droplet penetration into the powder bed and that granule consolidation and coalescence mainly took place in the nucleation, steady growth and rapid growth regimes. [ABSTRACT FROM AUTHOR]

The granulation process is considered to be a crucial operation in many industrial applications. The modelling of the granulation process is, therefore, an important step towards controlling and optimizing the downstream processes, and ensuring optimal product quality. In this research paper, a new integrated network based on Artificial Intelligence (AI) is proposed to model a high shear granulation (HSG) process. Such a network consists of two phases: in the first phase the inputs and the target outputs are used to train a number of models, where the predicted outputs from this phase and the target are used to train another model in the second phase to lead to the final predicted output. Because of the complex nature of the granulation process, the error residual is exploited further in order to improve the model performance using a Gaussian mixture model (GMM). The overall proposed network successfully predicts the properties of the granules produced by HSG, and outperforms also other modelling frameworks in terms of modelling performance and generalization capability. In addition, the error modelling using the GMM leads to a significant improvement in prediction. [ABSTRACT FROM AUTHOR]

Mass and population balance equations are used to describe the spray-on melt granulation process in a batch fluidized bed where coating and agglomeration can occur simultaneously. Two different models are considered to describe the agglomeration kinetics: the Equipartition Kinetic Energy (EKE) and Size Independent (SI) kernels, while the coating kinetics is represented by a power law. Based on experimental data obtained under different operating conditions (melt and air atomization flowrates, air fluidization velocity, seed diameter and bed temperature), the coating and agglomeration kinetic parameters are fitted to correctly predict the final particle size distributions. It is concluded that the SI kernel and the zero-order coating kinetics best describe the agglomeration and coating mechanisms, respectively. A correlation to predict the SI kernel from macroscopic variables and properties of the system is proposed. This tool can be used to provide starting kernel factors for solving the PBEs governing spray-on melt granulation in fluidized-bed granulators. Finally, a criterion to predict the limit of agglomeration occurrence is formulated. The criterion, which is developed in terms of dimensionless numbers that depend on process conditions and take into account mass, heat and momentum transfer phenomena, is found to be appropriate to predict the growth regime for fluidized-bed spray-on melt granulation of urea (i.e., the specific studied system). [ABSTRACT FROM AUTHOR]

Purpose: Twin screw hot melt granulation (TS HMG) is a valuable, but still unexplored alternative to continuous granulation of moisture sensitive drugs. However, knowledge of the material behavior during TS HMG is crucial to optimize the formulation, process and resulting granule properties. The aim of this study was to evaluate the agglomeration mechanism during TS HMG using a rheometer in combination with differential scanning calorimetry (DSC). Methods: An immiscible drug-binder formulation (caffeine-Soluplus) was granulated via TS HMG in combination with thermal and rheological analysis (conventional and Rheoscope), granule characterization and Near Infrared chemical imaging (NIR-CI). Results: A thin binder layer with restricted mobility was formed on the surface of the drug particles during granulation and is covered by a second layer with improved mobility when the Soluplus concentration exceeded 15% ( w/ w). The formation of this second layer was facilitated at elevated granulation temperatures and resulted in smaller and more spherical granules. Conclusion: The combination of thermal and rheological analysis and NIR-CI images was advantageous to develop in-depth understanding of the agglomeration mechanism during continuous TS HMG and provided insight in the granule properties as function of process temperature and binder concentration. [ABSTRACT FROM AUTHOR]

HPMC is a popular matrix former to formulate tablets with extended drug release. Tablets with HPMC are preferentially produced by direct compression. However, granulation is often required prior to tableting to overcome poor flowability of the formulation. While continuous twin screw granulation has been extensively evaluated for granulation of immediate release formulations, twin screw granulation of controlled release formulations including the dissolution behavior of the formulations received little attention. Therefore, the influence of the HPMC grade (viscosity and substitution degree) and the particle size of theophylline on critical quality attributes of granules (continuously produced via twin screw granulation) and tablets was investigated in the current study. Formulations with 20 or 40% HPMC, 20% theophylline and lactose were granulated with water at fixed process parameters via twin screw granulation. The torque was influenced by the viscosity and substitution degree of HPMC, but was not a limiting factor for the granulation process. An optimal L/S ratio was selected for each formulation based on the granule size distribution. The granule size distributions were influenced by the substitution degree and concentration of HPMC and the particle size of theophylline. Raman and UV spectroscopic analysis on 8 sieve fractions of granules indicated an inhomogeneous distribution of theophylline over the size fractions. However, this phenomenon was not correlated with the hydration rate or viscosity of HPMC. Controlled release of theophylline could be obtained over 24 h with release profiles close to zero-order. The release of theophylline could be tailored via selection of the substitution degree and viscosity of HPMC. [ABSTRACT FROM AUTHOR]

The evolution of the bacterial population during formation of denitrifying phosphorus removal granular sludge was investigated using high-throughput pyrosequencing. As a result, mature granules with a compact structure were obtained in an anaerobic/aerobic/anoxic (A/O/A) sequencing batch reactor under an organic loading rate as low as 0.3 kg COD/(m 3 ·d). Rod-shaped microbes were observed to cover with the outer surface of granules. Besides, reliable COD and simultaneous nitrogen and phosphorus removal efficiencies were achieved over the whole operation period. MiSeq pyrosequencing analysis illustrated that both the microbial diversity and richness increased sharply during the granulation process, whereas they stayed stable after the presence of granules. Some microorganisms seemed to contribute to the formation of granules, and some were identified as functional bacterial groups responsible for constructing the biological reactor. [ABSTRACT FROM AUTHOR]

Detergent agglomeration often involves the use of a highly viscous semi-solid (paste) binder. Such binders do not penetrate or disperse into a powder bed in the absence of an external force. Therefore mechanical dispersion is often employed to facilitate binder dispersion. Understanding the binder dispersion process is vital in ensuring consistent product quality. The present study aims to describe how viscous surfactant binders will undergo fragmentation/breakage within the mixer. The semi-solid binder can be considered to be “particles” and these powder coated binder particles (PCBPs) undergo a size reduction process with time. Other factors that influence the rate at which this size reduction process will occur include impeller speed, particle size and morphology. A typical detergent formulation will consist of a mixture of surfactant, zeolite (powder) and soda ash (powder). Two different grades of soda ash powder were studied: 130 μm light ash particles and 11 μm ground ash particles. This study reveals that larger particles maybe capable of exerting larger forces leading to more rapid breakage and deformation of the coated semi-solid binder fragments. This study also reveals that rougher particles are capable of penetrating the surface of the binder to a greater extent than smoother ones. In the case of zeolite, due to its smaller, more spherical particles and compact structure, the intermolecular forces within the semi-solid binder may be able to oppose the applied force (impact from the particles at the boundary) to a greater extent. This explains the slow change in the mean diameter of the zeolite PCBPs with time compared with the other two powders. At higher shear rates, there does not appear to be a significant increase in the final mass of the PCBPs when compared to the trials done at lower shear, instead the time taken to reach steady state in terms of both size and mass is shortened for all three powders, and for light and ground ash the lifespan of the PCBPs are shortened significantly, as the system passes the nucleation step and enters the wet-agglomerate regime. To conclude larger and rougher particles, with better flowability will disperse the highly viscous binder more effectively in a moving bed of powder. A high shear rate is recommended for better initial dispersion of the binder into powder formulations that consist of a large proportion of fine material. [ABSTRACT FROM AUTHOR]

Granulation of powdered materials in a drum-type high-speed granulator was studied. A mathematical model was constructed for describing the granulation in a high-speed granulator in which two processes, coagulation and disintegration, are combined. The constants of the integral transform core for coagulation and disintegration were determined from the experimental data obtained. The suggested mathematical model was shown to be adequate to the real process of granulation of a hydrophobic additive to asphalt concrete mix. [ABSTRACT FROM AUTHOR]

As a new and meaningful extension of the Pawlak rough set, multi-granulation rough sets (MGRSs) have attracted much attention and fruitful achievements have been reported in different aspects. By combining with fuzzy rough set, the paper introduces multi-granulation fuzzy rough sets in the covering approximation space, namely, covering-based multi-granulation fuzzy rough sets (CMFRS), which form the extension of fuzzy rough sets. We first investigate several important properties of lower and upper approximations of concepts in covering-based multi-granulation fuzzy rough sets and elaborate on the differences between the proposed models and the existing ones in literature. By employing the notions of reduct and exclusion of a covering, the paper studies the necessary and sufficient conditions for two CMFRS to generate identical lower and upper approximations of a target concept in the given covering approximation space. Finally, the relationships between the new models are explored in the paper. [ABSTRACT FROM AUTHOR]

This work focuses on microbial granulation in hybrid anaerobic reactors (HAR). Five HARs were used in two sets of experiments and all were seeded with the same inoculum. The volume of inoculum added was 10%, 20%, 30%, 40% and 50% in the first and 13%, 15%, 18%, 23%, and 27% in the second set of experiment. The volume of inocula added affects the sludge volume index, which in the present study proves to be important parameter for granulation. The results suggest that if SVI during the reactor start-up is kept between 150 and 210, reactors were able to form granules. Outside this range in the present set-up, no granulation was observed due to increased biomass wash-out, causing decreased SRT. Higher methane production was achieved in reactors with good granulation. The DGGE profiles show that the non-granulating systems had lesser diversity, due to increased wash out. Archaeal profile gave better correlation for granulation. Granulating reactors were rich in aceticlastic methanogens over hydrogen utilizing groups, especially Methanosaetaceae . Both Methanosarcina and Methanosaeta are required for better granulation as confirmed quantitatively. Bacterial profile of granulating reactors were rich in acetogens. SEM (Scanning electron microscopy) pictures show that granules are dominated by Methanosaeta -like microbes. Thus, the sludge characteristics at the start-up are of vital importance as they influence the sludge quality developed during the reactor operation and also the microbial communities retained. [ABSTRACT FROM AUTHOR]