Granulation Regimes Research Articles

Adapting the process conditions and performance in planetary roller melt granulation (PRMG) via the planetary spindle number

Continuous melt granulation with a planetary roller granulator is a new continuous method based on the orbital motion of planetary spindles driven by a rotating central spindle in a surrounding roller cylinder. Here the configuration of the processing section is a central design aspect, which defines the processing conditions and process performance. In this study, the number of applied planetary spindles as part of the module configuration was varied.As a result, a correlation between direct process parameters, processing conditions and process performance was identified. Hereby, the data normalization relativized successfully the effect of the module configuration. The results are also suitable to identify a module configuration and process settings in the context of a process optimization towards energy input efficiency or energy consumption. Finally, the accounting of the particle modification in terms of size was suitable to link the effect of the investigated parameters to the granulation regime.

Granulated Animal Feed and Fuel Based on Sea Buckthorn Agro-Waste Biomass for Sustainable Berry Production

The industrial harvesting of sea buckthorn (SBT) berries with twigs and subsequent pruning creates a large volume of lignocellulosic agro-waste. This study aimed to valorize this agro-waste as a raw material for animal feed and fuel granules, for developing a sustainable cascading SBT production scheme. Five SBT cultivars’ biomasses were characterized by analytical pyrolysis, mass spectrometry, and GC analysis. Condensed tannins, which are undesirable components for animal feed, were separated by extraction. The residue was analyzed for total protein, vitamins (A, C, and E), ash, crude fat, wood fiber, and macroelements (P, K, Ca, and Na), and showed great potential. The heavy metal (Cd, Hg, and Pb) content did not exceed the permitted EU maximum. Granulation regimes were elaborated using a flat-die pelletizer, KAHL 14-175. The digestibility and the amount of produced gas emissions were determined using in vitro systems that recreate the digestion of small ruminants. The investigation proved that SBT leaves and stems are a unique underutilized source of animal feed, used alone or in combination with others. Twigs, due to their thorns, were granulated and valorized according to standards for application as fuel. The scheme offered in this study enables SBT agro-waste utilization and sustainable SBT berry production.

Технология получения гранулированной биологически активной хитин-минеральной пищевой добавки, обогащенной пептидами

The possibility of obtaining dietary supplements based on chitin-mineral precipitates enriched with peptides by granulation in fluidized bed was studied. The dietary supplement is designed to correct mineral-deficient conditions and insufficiency of dietary fiber in the human diet. The objects of the study were products obtained during the complex processing of waste from the cutting of the northern shrimp (Pandalus borealis) by the electrochemical method – chitin-mineral complex and highly hydrolyzed protein product. The physicochemical properties of chitin-mineral precipitate and protein hydrolyzate have been studied. It has been established that peptides obtained from shrimp cutting waste are a promising binder for granulation of mineral precipitate, providing a granulate with a high degree of disintegration (not exceeding 7 min) and improved flowability (more than 8 g/s). It is also shown that the peptides enrich the resulting dietary supplement with essential amino acids. It was found that with an increase in the consumption of the binder, an improvement in the technological characteristics of the granules is observed (a decrease in bulk density and an increase in flowability), however, when the consumption of the binder exceeds 0.3 mg/g, the formation of a slurry-like mass preventing the formation of granules is observed. The effect of granulation regimes on the amino acid composition of granulated dietary supplements was studied. The finished form of dietary supplement in the form of granules was obtained.

Technology and Equipment for Plasma Electric Arc Granulation of Fused Welding Flux

The article outlines the main principles of granulation technology for fused welding flux using highly concentrated heat sources (e.g. plasma arc). Modern plasma equipment and methods of its use for producing new welding materials (plasma-granulated welding flux) from mineral raw materials and synthetic mineral alloys are described. The developed technology makes it possible to produce granulated flux in a wide range of fractional composition (from 0.2 to 3 mm). Studies have focused on the influence of granulation regimes (plasmatron moving speed, current, voltage, arc length) on formation process and the morphology of welding flux particles. Mineral raw materials used for granulation were igneous rocks (basalt, hornblendite) and synthetic mineral alloys. The results obtained during experiments on the use of highly concentrated heat sources for granulation of a fused welding flux confirm the feasibility and prospects of this technology. Typical equipment for air-plasma cutting is used, and no new complex technological equipment is required, therefore it eliminates large material and labor costs.

Quantitative Assessment of Mass Flow Boundaries in Continuous Twin-screw Granulation.

In pharmaceutical manufacturing, there is an increasing interest in continuous manufacturing. As an example for fast continuous processes in general of considerable complexity, this study was focussed on improving the understanding of twin-screw wet granulation. The impact of the liquid-to-solid (L/S) mass flow ratio on product quality (granules) as well as on downstream process operations (tableting) was investigated in detail. Initially two methods were used to define L/S ratio boundaries for the granulation regime in twin-screw wet granulation. It was shown that the first method, which is based on measuring the wet granule mass flow variation, can be used to define the upper L/S ratio boundary of the granulation regime. The second method, based on measuring the granule size distribution, can be used to define the lower L/S ratio boundary of the regime. Using these methods, the granulation regime for different formulations could be established. This information was then used to show that the formulation could be optimised such that the process is more robust (i.e. wider L/S ratio boundaries for the granulation regime). Also it could be used to optimise the formulation considering further downstream processing such as drying (using as little water as possible to reduce drying efforts) or tableting (obtain granules with optimised tableting properties). Preferably, the process should be performed close to the lower L/S ratio boundary of the granulation regime. In summary, these tools enabled the quantitative establishment of granulation regime boundaries in a twin-screw wet granulation process and can be used to optimise formulation and to create a robust process. Analogies to other continuous processes in completely different applications can be conceived.

The development of a growth regime map for a novel reverse-phase wet granulation process

The feasibility of a novel reverse-phase wet granulation process has been established and potential advantages identified. Granule growth in the reverse-phase process proceeds via a steady state growth mechanism controlled by capillary forces, whereas granule growth in the conventional process proceeds via an induction growth regime controlled by viscous forces. The resultant reverse-phase granules generally have greater mass mean diameter and lower intragranular porosity when compared to conventional granules prepared under the same liquid saturation and impeller speed conditions indicating the two processes may be operating under different growth regimes. Given the observed differences in growth mechanism and consolidation behaviour of the reverse-phase and conventional granules the applicability of the current conventional granulation regime map is unclear. The aim of the present study was therefore to construct and evaluate a growth regime map, which depicts the regime as a function of liquid saturation and Stokes deformation number, for the reverse-phase granulation process. Stokes deformation number was shown to be a good predictor of both granule mass mean diameter and intragranular porosity over a wide range of process conditions. The data presented support the hypothesis that reverse-phase granules have a greater amount of surface liquid present which can dissipate collision energy and resist granule rebound resulting in the greater granule growth observed. As a result the reverse-phase granulation process results in a greater degree of granule consolidation than that produced using the conventional granulation process. Stokes deformation number was capable of differentiating these differences in the granulation process.

Model-based analysis of a twin-screw wet granulation system for continuous solid dosage manufacturing

Implementation of twin-screw granulation in a continuous from-powder-to-tablet manufacturing line requires process knowledge development. This is often pursued by application of mechanistic models incorporating the underlying mechanisms. In this study, granulation mechanisms considered to be dominant in the kneading element regions of the granulator i.e., aggregation and breakage, were included in a one-dimensional population balance model. The model was calibrated using the experimentally determined inflow granule size distribution, and the mean residence time was used as additional input to predict the outflow granule size distribution. After wetting, the first kneading block caused an increase in the aggregation rate which was reduced afterwards. The opposite was observed in case of the breakage rate. The successive kneading blocks lead to a granulation regime separation inside the granulator under certain process conditions. Such a physical separation between the granulation regimes is promising for future design and advanced control of the continuous granulation process.

Granulation of snow: From tumbler experiments to discrete element simulations

It is well known that snow avalanches exhibit granulation phenomena, i.e., the formation of large and apparently stable snow granules during the flow. The size distribution of the granules has an influence on flow behavior which, in turn, affects runout distances and avalanche velocities. The underlying mechanisms of granule formation are notoriously difficult to investigate within large-scale field experiments, due to limitations in the scope for measuring temperatures, velocities, and size distributions. To address this issue we present experiments with a concrete tumbler, which provide an appropriate means to investigate granule formation of snow. In a set of experiments at constant rotation velocity with varying temperatures and water content, we demonstrate that temperature has a major impact on the formation of granules. The experiments showed that granules only formed when the snow temperature exceeded −1∘C. No evolution in the granule size was observed at colder temperatures. Depending on the conditions, different granulation regimes are obtained, which are qualitatively classified according to their persistence and size distribution. The potential of granulation of snow in a tumbler is further demonstrated by showing that generic features of the experiments can be reproduced by cohesive discrete element simulations. The proposed discrete element model mimics the competition between cohesive forces, which promote aggregation, and impact forces, which induce fragmentation, and supports the interpretation of the granule regime classification obtained from the tumbler experiments. Generalizations, implications for flow dynamics, and experimental and model limitations as well as suggestions for future work are discussed.

Quality by design for wet granulation in pharmaceutical processing: Assessing models for a priori design and scaling

Abstract The effective implementation of Quality by Design (QbD) for wet granulation requires quantitative models for design and scaling of granulators. This paper reviews that current state of the art of granulation modeling, especially with respect to QbD in the pharmaceutical industry. Our thesis is that the state of the art use of high shear wet granulation models for QbD should be at the intermediate level between the extremes of data-driven empirical models and first principles models, i.e., regime-based models. These models have a sound mechanistic basis and can be used for both formulation design and process scaling. Although not fully predictive, regime map approaches are a significant advancement over a typical design of experiments approach, where little is known about the process. In addition, regime maps are particularly useful for process scale-up/down. This review focuses on the status of wet granulation regime maps and critically assesses their applicability to real, rather than model formulations. The approach is illustrated by two case studies. The first case study evaluates the effect of changing the properties of one excipient, lactose, on formulation behavior. Changing lactose size distribution leads to substantial changes in both the formulation drop penetration time and dynamic yield stress, which can lead to changes in operating regime. A size measurement technique that accurately measures the fine end of the distribution is necessary to predict the effect of changing the lactose size distribution. The second case study uses the regime map approach to propose a design space and scaling rules for a high drug load formulation, and successfully validate the scaling rules for scaling from a 10 l to a 75 l granulation. This case study emphasizes the importance of spray distribution to avoid operation in the mechanical dispersion regime and subsequent lump formation as a granulation is scaled up.

Monitoring Granulation Rate Processes Using Three PAT Tools in a Pilot-Scale Fluidized Bed

The purpose of this research was to analyze and compare the responses of three Process Analytical Technology (PAT) techniques applied simultaneously to monitor a pilot-scale fluidized bed granulation process. Real-time measurements using focused beam reflectance measurement (Lasentec FBRM) and near-infra red spectroscopy (Bruker NIR) were taken by inserting in-line probes into the fluidized bed. Non-intrusive acoustic emission measurements (Physical Acoustic AE) were performed by attaching piezoelectric sensors on the external wall of the fluidized bed. Powder samples were collected at regular intervals during the granulation process and characterized offline using laser diffraction, scanning electron microscopy, stereo-optical microscopy and loss on drying method. PAT data comprising chord length distribution and chord count (from FBRM), absorption spectra (from NIR) and average signal levels and counts (from AE) were compared with the particle properties measured using offline samples. All three PAT techniques were able to detect the three granulation regimes or rate processes (wetting and nucleation, consolidation and growth, breakage) to varying degrees of sensitivity. Being dependent on optical signals, the sensitivities of the FBRM and NIR techniques were susceptible to fouling on probe windows. The AE technique was sensitive to background fluidizing air flows and external interferences. The sensitivity, strengths and weaknesses of the PAT techniques examined may facilitate the selection of suitable PAT tools for process development and scale-up studies.

The use of Stokes deformation number as a predictive tool for material exchange behaviour of granules in the ‘equilibrium phase’ in high shear granulation

The objective of this study was three-fold; to investigate the different mechanisms of material exchange during the equilibrium phase of the granulation process and whether these mechanisms are consistent with the mechanisms described in the growth regime map, to study how material properties and process conditions affect these exchange mechanisms, and to correlate Stokes deformation number to the exchange mechanisms. Microcrystalline cellulose (MCC), α-lactose, microfine cellulose (MFC), and dextrin were granulated using water as a binding agent. Once in the equilibrium phase, 5% (w/w) of the granular mass was replaced with wet tracer granules, after which the granulation process was continued. Granules were typically of a size of approximately 1 mm in diameter. Therefore, these granules can also be called pellets. Tracer experiments show indeed solid material exchange can take place in the equilibrium phase of the high shear granulation process. Tracer material was equally dispersed throughout the whole batch for all materials tested. However, the granulation time needed to reach this homogeneous distribution varied with material and granulation conditions. Three different mechanisms of material exchange were identified: exchange by disintegration, where granules are rapidly crushed and formed to granules again; exchange by deformation, where abraded granule fragments immediately fuse with other granules; and exchange by distribution, where there is a prolonged period over which both tracer and standard granules stay intact, followed by uncontrolled growth and exchange of material. It was found that it is possible to shift between the mechanisms by changing the process conditions, e.g., changing viscosity or amount of binder liquid. These observations indicate that by choosing the appropriate process conditions improved distribution of small amounts of insoluble materials in the granules can be obtained. A relation exists between the exchange mechanisms and the growth regime map: the disintegration mechanism resembles ‘crumb behaviour’, the deformation mechanism resembles ‘steady growth’, and the distribution mechanism resembles ‘nucleation’ and ‘induction growth’. Unfortunately, Stokes deformation number cannot be used as a predictive tool when low viscosity binders like water are used, due to the importance of viscosity in the equation. However, this number is one of the variables of the growth regime map. Since the exchange mechanisms correspond to the granule growth mechanisms in the regime map, alternatively colour experiments might be used to reveal the granulation regime.

Investigation of Heat Exchange in the Water Granulation of Sulfur

Three possible granulation regimes are established experimentally. A dimensionless complex describing the boundaries of effective zones of the granulation equipment, and the dependence of its operating regimes on the temperatures of the melt and cooling water are cited.

Fluidized drum granulation: studies of agglomerate formation

Agglomerate formation in fluidized drum granulation was studied experimentally using a 0.3 m diameter laboratory fluidized drum granular. Glass ballotini of various sizes were coated molten paraffin wax. The effect of particle size (1.5 to 8 mm), liquid spray rate (17 to 43 g/min) and drum speed (20 to 40 rpm) on the fraction of agglomerates formed was measured. The formation of agglomerates was controlled by collisions between wetted granules in the falling particle curtain in or near the spray zone. There is a sharp transition between high fractions of agglomerates (non-inertial regime) and almost no agglomerates (coating regime) as particle size increases. This transition point increases strongly with increasing liquid spray rate but is only a slight function of drum speed. These results agree, qualitatively and quantitatively, with the granulation regime analysis proposed by Ennis. Tardos and Pfeffer, Powder Technol., 65 (1991) 257 which is based on the balance between inertial energy and viscous dissipation during a collision between two wetted granules. Analysis of the data shows the characteristics collision velocity is low, of the order of 0.02 m s −1, and this is consistent with agglomerates forming in the falling particle curtain near the spray zone. A better understanding of particle-particle and particle-binder interactions in the spray zone is needed to extend the theoretical analysis and develop design and scale-up rules.

The effect of process parameters on drum granulation of fertilizers with broad size distributors

The effect of moisture content, particle size distribution and binder properties on the granulation of ammonium sulphate (AS), monoammonium phosphate (MAP) and diammonium phosphate (DAP) were investigated using experiments carried out in a 0.31 m diameter laboratory granulation drum. Broad initial size distributions were used to simulate recycle size distributions in operating granulation circuits. Granulation extent increases with the available solution phase for a given fertilizer salt. However, differences in granulation extent for different salts cannot be explained by their differences in solubility alone. Other properties of the solution phase binder, especially viscosity, are also important. At low moisture content and for low binder viscosity (MAP), an equilibrium size distribution is reached in less than 5 min. At higher moisture contents and binder viscosities (DAP), granulation continues up to at least 15 min before equilibrium size distribution is reached. The initial size distribution has a strong and complex effect on the granulation process. This extent of granulation goes through a maximum as the proportion of fine (minus 1 mm) in the initial size distribution increases. This effect is attributed to the changes in granule porosity and deformability. A two-stage granulation mechanism is proposed based on the analysis of granulation regimes given by Ennis . In the first stage (non-inertial regime), successful coalescence is independent of particle sizes. An equilibrium granule size distribution is quickly attained. In the second stage (inertial regime), at higher moisture contents, preferential coalescence predominates, leading to a significant growth of the large granules. The size distribution is subsequently widened. This mechanism is consistent with the experimental results. The analysis of granulation regimes given by Ennis successfully explains the effects of process parameters (liquid content, binder viscosity and initial size distribution) on the extent of granulation and the shape of the granule size distributions.

A microlevel-based characterization of granulation phenomena

Past granulation research has been essentially restricted to a macroscopic study of the impact of operating variables on granule morphology. While fundamental groundwork regarding agglomeration forces has been laid by pioneers such as Rumpf, little progress towards an a priori characterization of microlevel phenomena in terms of macroscopic process variables has been achieved. The present work centers on this microscale and introduces a classification of granulation mechanisms based on the collisional dissipation of relative particle kinetic energy. The mechanism of granule coalescence is, in part, a function of a dimensionless binder Stokes' number St v, which is a measure of the ratio of granule collisional kinetic energy to the viscous dissipation brought about by interstitial binder. The Stokes' number provides a convenient classification of granulation regimes. For small St v, coalescence hinges on the presence and distribution of binder and is independent of particle kinetic energy and binder viscosity. In this regime, binder viscosity controls the rate of granule consolidation and ultimate granule voidage. For the case where the maximum St v is of the order of St* v, increases in binder viscosity increase coalescence rate as traditionally expected. Here St* v is a critical Stokes' number, being a known function of the volume of binder deposited on the bed. Finally, for large St v, only granule coating is possible. Fluid-bed granulation and defluidization experiments supporting this simple classification of granulation regimes is presented. Implications regarding successful granulation operation are drawn.