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Second International Workshop on Granulation 22 – 25 June 2004, University of Sheffield

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ABSTRACTS SESSION I: HIGH SHEAR PROCESSES

HIGH SHEAR GRANULATION IN THE PHARMACEUTICAL INDUSTRY; INHOMOGENEITY PHENOMENA.

Kaspar van den Dries#, Herman Vromans#&

#N.V. Organon, AKZO-NOBEL, P.O. Box 20, 5340 BH Oss, The Netherlands &Faculty of Pharmacy, University of Utrecht, P.O. Box 80082, 3508 TB Utrecht, The Netherlands

In the pharmaceutical industry high hear granulation is a commonly used process step in the production of a solid formulation. Because of regulatory guidelines and product quality assurance, an important granule requirement is homogeneity. However, often granule inhomogeneity is observed, expressed as a granule size-dependent variation in composition of the granules [1-4]. As a consequence of segregation during subsequent process steps this might introduce content uniformity problems. In order to solve these quality problems the mechanisms involved in the formation of non-homogeneous granulates have to be elucidated.

A research project focused on this subject revealed that at least three different mechanism are of importance;

1. The mechanism of granule formation (nucleation); the granule inhomogeneity already exists in the first minute of the granulation process, indicating that nucleation plays an eminent role. To investigate the early seconds of high shear granulation the process was frozen with liquid nitrogen. From this approach the following insights have been achieved: The mechanical agitation results in binder dispersion. Parallel to the dispersion process penetration of the binder liquid leads to the formation of granules. This prevents complete dispersion. The dynamic strength of the granules determines whether freshly formed granules survive the shear forces.

2. Preferential growth during layering; Layering growth experiments with single granules showed that fine primary particles have a higher affinity for granule growth than coarse particles. This results in an accumulation of the fine particles in the granules. It was argued that fine particles can enter the surface pores, while coarse particles cannot. This provides “a headstart” for the fine particles in the powder mix with respect to growth. A model based on this hypothesis was able to describe the experimental results quantitatively.

3. Granule breakage behaviour; The breakage behavio ur in the high shear mixer was investigated with tracer experiments [2]. Comparison of these results with the granule homogeneity showed that there is a interrelationship between granule breakage and the drug distribution over the granules. Granule breakage results in a continuous exchange of (primary) particles between granules. This yielded a homogeneous distribution. On the other hand, when there is minimal breakage, intact granules function as kernels for preferential growth. Consequently, the development of a poor distribution depends on the constituents’ particle size differences.


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Unravelling the mechanism is the first step towards a high quality product. In addition, experiments were performed to investigate the influence of process and formulation conditions on the above described mechanisms. This level of understanding can prevent granule inhomogeneity in the future. Eventually, this scientific approach to process development must results in proper control of high shear granulation and adequate granule properties.

1. Hapgood, K.P., Hartman, H.E., Kaur, C., Plank, R., Harmon, P., Zega, J.A., 2002. A case study of drug distribution in wet granulation. World Congress of Particle Technology 4, Sydney, Australia (21-25 July).

2. van den Dries, K., de Vegt, O., Girard, V., Vromans, H., 2003. Granule breakage phenomena in a high shear mixer; influence of process and formulation variables and consequences on granule homogeneity. Powder Technol. 133, 228-236.

3. van den Dries, K., Vromans, H., 2002. Relationship between inhomogeneity phenomena and granule growth mechanisms in a high shear mixer. Int. J. Pharm. 247, 167-177.

4. Vromans, H., Poels -Janssen, H.G.M., Egermann, H., 1999. Effects of high shear granulation on granulate homogeneity. Pharm. Dev. Technol. 4, 297 -303.

EMPIRICAL TO MECHANISTIC MODELLING IN HIGH SHEAR GRANULATION – EXAMPLES FROM THE PHARMACEUTICAL INDUSTRY

I. Niklasson Björn, A. Jansson, M. Karlsson, S. Folestad and A. Rasmuson AstraZeneca Centre of Excellence for Process Analytical Technology P A R &D Mölndal, Sweden

Wet granulation in high shear mixers is an important unit operation step often used in development and manufacturing of pharmaceutical oral solid dosage forms. It is a complex process step and the knowledge about the fundamental mechanisms behind it is limited. To improve the understanding, it is important to find different ways to model and monitor the process to enable predictive scale-up and control of the process. Different types of models have been used to describe the dynamic behaviour of the impeller torque and the granulate growth.

A change in the impeller torque is a direct measure of changes in the flow pattern and/or changes in material properties within the mixer. However, the interpretation of the impeller torque measurements is not trivial. The impeller torque has been modelled for both the dry and wet mixing phases. In the dry mixing phase a mechanistic model found in the literature was used. In the wet mixing phase a multivariate process model was used.

The model used in the dry mixing phase was slightly modified and a new term was added. Experiments where made with microcrystalline cellulose. The results showed good agreement between the modified model and the experimental data. The model was also used for predictions.

For the wet mixing phase the multivariate process model was constructed from timely measurements of impeller torque, moisture content, particle size, density and NIR spectra. The multivariate model was able to successfully explain the variation in the impeller torque for different operating conditions and material properties.

To describe the granulate size distribution growth a population balance model was developed. The theory of population balance modelling requires knowledge of how and to what extent two particles are likely to coalesce or break. In the population balance equation, the probability function for coalescence is known as the coalescence kernel. A coalescence kernel has been constructed, where theories from the macro- and micro-level have been combined. The effect of different process parameters like impeller speed, initial particle size, bowl size, liquid viscosity,


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addition time and wet massing time have been included. A simple model of the shear forces was found to be related to the impeller to rque exerted by the in the bowl.

WET GRANULATION IN A BATCH HIGH SHEAR MIXER

Khashayar Saleh, Lilian Vialatte & Pierre Guigon Dépt. Génie Chimique, Université de Technologie de Compiègne, France

This study deals with the wet granulation in a high shear mixer. The experimental apparatus is a laboratory scale "Lödige" granulator, with a maximum volume of 20 L and equipped with a chopper and an pneumatic atomising system.

The main objectives of the study are, firstly, to point out the effect of binder-solid interactions on mechanisms of granulation and, secondly, to establish the technological signature of the granulation device.

Two kinds of alumina with different particle size distributions (alumina SH100 and alumina SH30) were granulated using various liquids having different surface tensions, viscosities, binder concentrations, densities, ... (water, aqueous solutions of polyethyleneglycol or polyvinylic alcohol).

Experimental results showed that the granulation process proceeds generally through a three distinct growth regimes independent of the nature of the powder, the binder liquid or the operating conditions. However, the transition between different regimes depends on the physico chemical properties of solids and liquids, on operating conditions and on the experimental procedure.

Analysis of samples removed from the granulator at different time intervals permitted to point out growth mechanisms involved in each regime as follows:

After a first stage in which the granulation mechanism is the nucleation of primary particles (regime 0), it appears a first regime in which there is no creation of new agglomerate species. During this regime, there is a balance between attrition phenomena which create fine particles or agglomerates in the one hand and fine consuming growth mechanisms (agglomeration, layering) on the other hand. In the second regime, granules grow by non-preferential layering of the fine agglomerates onto the surface of the other species. The phenomena that governs the transition between the first and the second regime are the densification of the granules and the binder transport to the granule surface. Finally, when the fine agglomerates are entirely picked up, a third regime appears in which the granulation mechanism is a preferential coalescence mechanism of small and coarse granules.

A physico-chemical approach based on the individual surface free energy of the powder and the binder liquids was used to assess the substrate-binder interactions. A unifying correlation to predict the three stage granulation profile and transition points was also developed.

Finally, scale-up experiments, carried out on an industrial scale granulator, confirmed the three stage granulation profile revealed in the laboratory scale granulator.


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MECHANISMS IN HIGH VISCOSITY IMMERSION-GRANULATION

S.L. Rough1, D.I. Wilson1, A.E. Bayly2 and D.W. York2

1Department of Chemical Engineering, University of Cambridge, UK 2Procter and Gamble Ltd, Newcastle Technical Centre, Longbenton, UK

An atypical high shear granulation process is investigated in which a fine inert powder is bound with a highly viscous surfactant paste. The mechanism comprises adsorption of powder particles onto paste fragments, breakage of powder-coated paste granules, micro-mixing of the granules with absorption of the powder, granule growth via coalescence, and finally granule consolidation. These stages are supported by micrographic and granule size distribution data. The agglomeration process features two main mechanisms, namely binder distribution followed by granule consolidation and coalescence, with their key transitions exhibiting a different dependency upon operating parameters.

A number of time-dependent consistency regimes can be identified and quantitatively described by parameters obtained from bulk tapping compaction tests. Various dynamic granule characteristics are inferred from these pseudo-steady state bulk parameters, and are used to track the agglomeration process, the results of which are consistent with the Iveson et al.1 steady state agglomeration regime maps. Of particular interest is the trend in Hausner ratio, which provides information on the inter-granular friction and cohesivity.

The effects of paste/powder composition, paste rheology and mixing speed upon the transition rate can be explained physically in terms of adsorption, viscous and mechanical energy dissipation mechanisms. In summary, the work introduces a preliminary analysis of an immersion-granulation mechanism in which a number of key features are identified. The results suggest that a fundamental investigation of steady state and dynamic system properties at both the macro- and micro-scale would be highly advantageous.

1. Iveson S.M., Wauters P.A.L., Forrest S., Litster J.D., Meesters G.M.H. and Scarlett B. (2001) Growth regime map for liquid-bound granules: further development and experimental validation, Powder Tech., 117, p.83-97, 2001.

AGGLOMERATION PROPERTIES FOR GLUTEN AND GLUTEN FREE CEREALS FLOURS BY WATER ADDITION AND SHEARING - MIXING RHEOLOGY COUPLED WITH MICROSCOPIC OBSERVATION

Hebrard A., Oulahna D. Laboratoire de Génie des Procédés des Solides Divisés, Ecole des Mines d'Albi-Carmaux, France

The agglomeration properties of gluten content cereals such as durum wheat semolina and gluten free cereals such as amaranth, corn, manioc, quinoa and buck wheat flour, have been investigated. The different states of agglomeration have been identified by the evolution of mixing rheological properties under binder addition and shearing conditions determined by a mixer torque rheometer (MTR) [Hancock, 1994]. Surface state alterations during agglomeration have been observed by environmental microscopic observations (ESEM) which do not impose sample pre- treatment.

All these samples present the same rheological footprint under specific hydration and shear rate, three agglomeration states can be identified. Progressively, particles agglomerate and form aggregates which coalesce, their size increases up to the development of a paste, then the


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maximum viscosity is reached. Further addition of water results in paste dilution and the viscosity decreases.

The agglomeration properties of all these samples and microscopic observations, in this study allows comparison of the hydration rate, the mixing viscosity to reaching a specific state of agglomeration, the surface state of the agglomerates and the structure of the links formed between particles composing the agglomerates.

GRANULAR FLOW IN A PLANETARY MIXER B.F.C. Laurent1 and D.I. Wilson2 1 Institute for Manufacturing, Cambridge University, Department of Engineering, Cambridge CB2 1RX, UK 2 Department of Chemical Engineering, University of Cambridge, Cambridge, CB2 3RA, UK

Granulation is an important step in drugs manufacturing processes. Here, flow patterns in dry systems and during wet-mass granulation were characterised using Positron Emission Particle Tracking. Powder flows were studied first in a planetary mixer where two different regimes were identified. In a dry state, the material flows along a torus formed by the beater of the agitator. The angular velocity and total speed scaled with the agitator speed, showing that powder flow is controlled by the number of blade passes. When granulation proceeds, the flow fields in the core showed the presence of another torus situated above the one observed with the dry system, creating a region of high shear where both tori meet. Related work using a simplified mixer showed how granular flows may be related to torque rheometry. This opens the prospect of designing new continuous processes for the pharmaceutical industry in order to implement leaner manufacturing methods and just- in-time techniques of production.


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SESSION II: FLUIDIZED BED PROCESSES

STUDIES OF FLUID BED GRANULATION IN AN INDUSTRIAL R&D CONTEXT

Renee Boerefijn Following a brief overview of recent developments in laundry powder processing and current drivers and trends, a review will be presented of collaborative research between Unilever R&D and Sheffield University on fluidised bed granulation. These fall apart into 4 areas:

1. Contact zone studies

2. Growth similarity for non- ideal systems

3. Growth and breakage on balance

4. Scale-up rules based on similarity

Together, this lays the broad ground-work for fluidised bed granulation. Some concluding remarks provide pointers for the future of research in this area.

SPRAY GRANULATION, AGGLOMERATION AND COATING PROCESSES USING CONTINUOUS FLUIDIZED BED TECHNOLOGY

Michael Jacob Glatt Ingenieurtechnik GmbH / R&D Nordstrasse 12, 99427 Weimar, Germany

Fluidized bed techniques are widely used in all fields of industry. The range of application includes both heat and mass transfer processes (for instance cooling and drying calcination) and complex multi-phase processes like agglomeration, spray granulation and coating.

In many field of the industry products created using spray granulation or agglomeration processes obtain growing importance. The fields of application include products like instant food, instant drinks, mixtures and single components in the food, pharmaceutical or chemical industry. The products range from dustfree spray-granulated fine chemicals with high bulk density and high resistance against abrasion to instant drinks for health care which are homogeneous in composition, free flowing, easily wettable and fast to dissolve in liquids.

To manufacture these kinds of products continuous fluidized bed processes are more than suitable.

Based on basic principles of fluidized bed processes two main types of continuous fluidized bed plants were developed. These types will be described in the following chapters.

The first version ( fig. 1 ) is a fluidized bed unit with rectangular design of bottom screen. The bottom screen is used to equalize the flow of process air and is the lower border of the fluidized bed. In the normal case the product discharge is realized using a rotary valve. The discharge flow rate can be adjusted by changing the speed of this volumetric dosing device. Normally an internal classifying of the product flow in the unit is not rea lized. In standard units the dedusting of the


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exhaust is done using an integrated bag filter system. The filter bags are cleaned by pulse back air. By using internal filter systems all solid streams are kept inside the process room and additional conveying systems to recycle solids are not necessary. If needed this version of fluidized bed units can be delivered alternatively with an external dedusting system or wet scrubber. The main advantage of this unit is the possibility to carry out multi-step processes in one apparatus. In fig. 1 a combination of an agglomeration or spray granulation process with a cooling process is shown. The section below the bottom screen can be devided into several inlet air chambers to distribute the air flow to the different process steps and feed different air qualities to the fluidized bed.

clean gas-chamber

filter systemintegrated

expansionchamber

fluidized bedchamber

inlet airchambers

spray systemtop-spray

bottom-spray

solid feedseeds / powder / wet solids

Process airfor fluidization

and drying

Process airfor fluidizationand cooling

product discharge

bottom screen

Fluidized bed granulator / coater for continuous processing - type GFG

Figure 1

In contrast with the unit of fig. 1 in fig. 2 a fluidized bed unit with circular design of the bottom screen is shown. Typical for this special version of fluidized bed unit is the central classifying discharge pipe for continuous product discharge. The upper end of this vertical pipe is fitted direct in the bottom screen. The bottom screen is used to equa lize the flow of process air and is the lower border of the fluidized bed. A second air flow is fed to the discharge pipe. The flow velocity is adjusted in such a way that small particles are blown back to fluidized bed. Particles with a falling velocity higher than the flow velocity in the discharge is will be discharged. Because of that mechanism the particles size of discharged solids can be adjusted and the product is free of dust. These version of fluidized bed units are normally equipped with external dedusting systems. The recovered dust of external dedusters can be recirculated to the agglomeration or spray granulation process.


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Fluidized bed granulator for continuous processing - type AGT

segregation chamber

expansion chamber

fluidized bed chamber

inlet air chamber

dust

seeds

starting material

spray systemtop-spray

bottom-spray

process airfor fluidization

and drying

classifying air

product

discharge pipe

bottom screen

Figure 2

In all agglomeration processes or in the special case of spray granulation liquids are sprayed into the fluidized bed. In order to do that spray nozzles are installed in the process room to distribute the liquid. Different spray systems can be used to spray either on top of the fluidized bed ( top-spray ) or direct upwards into the fluidized bed ( bottom-spray ) . Both spray systems can be used in both versions of fluidized bed units.

This article focuses on continuous processing options where liquids are sprayed onto fluidized products.

The article will focus on both general principles and case studies of large-scale industrial applications. For this reason the audience can enter the field of continuous fluidized bed technology and recognize its potential for industrial application.

ON THE PREDICTABILITY OF FLUIDIZED BED SPRAY GRANULATION: ANALYSIS OF PARTICLE POPULATIONS AND TRANSPORT PHENOMENA

Stefan Heinrich Otto-von-Guericke-University Magdeburg Institute of Process Equipment and Environmental Technology Universitätsplatz 2, D-39106 Magdeburg e-mail: [email protected]

The fluidized bed spray granulation (FBSG) is a process used for the production of granular high-quality, free- flowing, low-dust and low-attrition solids originating from liquid products, e. g. solutions, suspensions, melts and emulsions. The advantage is the coupling of the wetting, drying, particle enlarging, shaping, homogenisation and separation processes and the the production in a single processing step. Especially for large production units a continuous operation of the FBSG is desirable. The continuous granulation process presents, unlike to the batch-operation, the advantage to operate the plant under stationary condition at high throughputs. The stationary operation point is reached, provided constant granulate spectrum beside


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constant mass flows and constant thermal conditions, whereby initially fed granulates have to be removed at all. Sometimes this unsteady phase lasting up to a few hours.

This contribution presents calculations of the transient behaviour of the particle size distributions in the fluidized bed and in the product flow with regard to the number of particles, surface, mass and volume of particle, of the air temperature, of the air humidity, of the wetting efficiency, of the temperature of the liquid film around the particles, of the particle temperature and of the pneumatics (porosity, Reynolds number, velocities) during the unsteady start-up period, including all input and output particle (disperse phase) and mass (continuous phase) flows. Seeds are produced in several ways: (1.) Particle attrition, (2.) Overspray (nucleation) are non deposited dried drops, (3.) Agglomeration of wet and dry particles, (4.) by a external crusher. Therefore, the population balance model takes into account the seeds formation (fines generation). An dynamic oscillating behaviour, which may occurre during the unsteady start-up phase, caused by classifying and milling processes, is discussed. The aim of the examinations is to study the stability behaviour of the FB (Fig. 1).

Furthermore, the complex correlations of a number of microprocesses, spraying, wetting, drop deposition, heat transfer, drying / evaporation and mass transfer considering that the solid dispersion were studied, and transient three-dimensional distributions of the air humidity, the air temperature, the particle wetting efficiency, the liquid film temperature, the particle temperature, the local liquid loading and liquid deposition (spraying zone) and the local evaporation rate were calculated (Fig. 2).

The population balance model (Fig. 3) and the heat and mass transfer model (Fig. 4) was evaluated in a semi- industrial fluidized bed pilot plant of the institute.

stable behaviour (coarse milling) unstable behaviour (fine milling)

Figure 1. Calculated particle size distributions of a continuous external separation process.


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Figure 2a: Unsteady distributions at a top-spray injection onto a fluidized bed at time t =

100 sec with low solid dispersion (Dvertical = 0.01 m²/s, Dhorizontal = 0.001 m²/s).

Figure 2b: Unsteady distributions at a top-spray injection onto a fluidized bed at time t =

100 sec with high solid dispersion (Dvertical = 0.1 m²/s, Dhorizontal = 0.01 m²/s).


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Bed - Measurement Bed - Simulation

Product - Measurement Product - Simulation

Figure 3. Comparison of measured and simulated particle size distributions of a continuous

internal separation process.

heig

ht a

bove

dis

tribu

tion

plat

e [m

]

heig

ht a

bove

dis

tribu

tion

plat

e [m

]

radius [m]

view on 120 - 300 degree plane

Figure 4. Measured stationary spatial air temperature distributions of a water sprayed FB

of plastic beads.


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PARTICLE DESIGN AND EVALUATION OF DRY CO2 RECOVERY SORBENT WITH A LIQUID HOLDING CAPABILITY Satoshi Kimura, Masamitsu Adachi, Reiji Noda and Masayuki Horio Tokyo University of Agriculture and Technology, Graduate School of BASE, 2-24-16, Nakamachi, Tokyo, 184-8588, Japan e-mail: [email protected]

For CO2 capture at high temperature/high CO2 partial pressure conditions, new dry CO2 removal sorbents were developed based on the recently developed lithium silicate with additives to accelerate CO2 sorption. To avoid adhesion and defluidization associated with the liquid carbonate phase formation in the temperature range of 500-600 C, sorbent particles were designed so that the liquid lithium carbonate cannot really wet the sorbent surface. To achieve this the lithium silicate fine particles granulated forming the core of a sorbent particle were coated with a layer of coarse alumina particles. Different types of sorbents were manufactured by granulation and coating with different ceramic sol binders and different prescriptions in a tumbling fluidized bed. Minimum fluidization velocity, fluidizing behavior and adsorption/desorption properties of the sorbent particles were determined in a laboratory scale fluidized bed reactor (i.d.,0.03m) in the temperature range up to 1073K. In cyclic adsorption/desorption conditions, gradual decrease both in over all conversion and maximum adsorption capacity took place. Nevertheless, the performance obtained for the sorbent manufactured with alumina sol was found successful with no defluidization and with high adsorption capacity of 50% in conversion (10wt% including the coat layer) over 60cycles.

PRELIMINARY DEM SIMULATIONS OF FLUIDISED BED GRANULATION

K. D. Kafui & C. Thornton School of Engineering, The University of Birmingham, UK

A fully 3D granular dynamics fluidised bed model based on the Distinct Element Method (DEM) has been developed and adapted for a preliminary ‘proof-of-concept’ simulation of fluidised bed granulation (Thornton & Kafui, 2004). In the model (Kafui et. al, 2002), the discrete particle-particle or particle-wall interactions are based on theoretical contact mechanics in which the actual material properties are utilised, ensuring that these properties govern the evolution of contact forces and the resultant kinematics. The gas phase is modelled as a continuum and the compressible Navier-Stokes equations of motion are solved using an adapted form of Patanker’s SIMPLE methodology (Kuipers et. al, 1993).

The concept explored here is that of a spray zone notionally represented as a conical region of fine mist of ‘adhesive’ or liq uid where the apex of the zone is the spray source. Discrete particles which enter this region pick up ‘adhesive’ or liquid film, the amount (volume) and/or strength (surface energy or viscosity) of which depends on the distance from the source and the time spent in the zone.

For the ‘adhesive’ spray zone concept, surface energy based on the JKR theory is the notional adhesive. A ‘drying’ adhesive bond between two particles is mimicked by increasing the interface energy up to an asymptotic limit determined by the initial bond interface energy. The duration of the activity of the surface energy of a particle outside the spray zone is limited, with the surface energy ‘drying’ during this period and becoming inactive if no bonding occurs before activity ceases.


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Liquid spray is employed as the active binding medium in the spray zone for the second modelling concept. Here, particles in the spray zone get a dosage of liquid on the surface, the volume of dosage being a function of the time spent in the spray zone and the distance from the spray source. Pendular liquid bridges are formed when a particle with ‘wet’ surface liquid makes contact with another particle. The liquid bridge forces are evaluated using the formulations of Lian et. al, 1993, and the viscosity of the liquid in a bridge or at a particle surface is increased functionally from a ‘wet’ value to a ‘dry’ value according to its age. For viscosities below a set proportion of dry viscosity dubbed the migration limit, it is assumed that liquid migration can occur from a bridge to a bridgeless contact on the same particle, the driving force being the difference between the migration limit and the viscosity in the bridge.

The adhesive conceptual formulation of the spray zone has been employed in a preliminary simulation of the fluidised bed granulation of a bed of 100,000 Geldart group A particles (five sizes, 45 mm – 55 mm). Video sequences of the evolution of granules and bonds will be presented along with evolving granule size distributions. Work using the liquid spray formulation is still in progress.

1. Thornton, C. & Kafui K.D. (2004). Fully 3D DEM simulations of fluidised beds including granulation. To be presented at Fluidization XI, Ischia, 9-13 May, 2004.

2. Kafui, K.D., Thornton, C. & Adams, M.J. (2002). Discrete particle -continuum fluid mo delling of gas-solid fluidised beds. Chemical Engineering Science, 57, 2395-2410.

3. Thornton, C. & Yin, K.K. (1991). Impact of elastic spheres with and without adhesion. Powder Technology, 65(1-3), 113-123.

4. Kuipers, J.A.M., van Duin, K.J., van Beckum, F.P.H. & van Swaaij, W.P.M. (1993). Computer simulation of the hydrodynamics of a two -dimensional gas-fluidised bed. Computers in Chemical Engineering 17(8), 839-858.

5. Lian, G., Thornton, C. & Adams, M.J. (1993). A theoretical study of liquid bridge forces and stability between two rigid spherical bodies. Journal of Colloid and Interface Science, 16, 138-147.

CONCEPTS TO IMPROVE THE EFFICIENCY OF FOOD AGGLOMERATION

S. Palzer Nestlé Product Technology Centre, Lange Strasse 21, D-78224 Singen

In the food manufacturing industry several agglomeration technologies are applied: fluidised bed agglomeration, steam jet agglomeration, agglomeration during drying and pressure agglomeration like extrusion, roller compaction or tabletting. There are some concepts, which can be applied across the length scale to improve the efficiency of agglomeration processes.

During various agglomeration processes moisture is added to the powder particles to increase the adhesion forces by approaching or exceeding the glass transition temperature Tg of amorphous substances. Calculating Tg for various moisture contents enables to identify for different processes suitable moisture/temperature combinations.

Another approach is to describe pressure agglomeration by applying the laws of bulk solid handling. The results obtained by trials and calculations allow characterising powdered foodstuffs including their yielding and compaction behaviour. Thus suitable axial and radial stress combinations and equipment design for the different stages of pressure agglomeration processes can be defined.


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BREAKAGE KINETICS DURING FLUIDISED BED GRANULATION

H.S. Tan, A.D. Salman and M.J. Hounslow, Particle Products Group, Department of Chemical and Process Engineering, The University of Sheffield

It is widely acknowledged that in the great majority of granulation processes there are size enlargement (agglomeration) processes and size reduction (breakage processes) active simultaneously. Yet most modelling studies account only for agglomeration. The reasons for this defect are two fold: first agglomeration-only models seem to give a good description of the process and secondly even quite high- fidelity measurements of particle size distribution do not allow model discrimination between agglomeration-only and agglomeration-plus-breakage models. This defect poses a considerable problem in seeking to extrapolate or scale-up by means of the model since in some processes the breakage rate might be quite high and so the actual agglomeration rate is much greater tha n that predicted by the model.

In this paper we user specially made tracer particles to show the extent of breakage and to quantify its kinetics. We address the issue of discriminating between attrition and fragmentation and are able to draw conclusions about the effects of granule age and size.


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Figure 1 - Instrumented roll compactor

SESSION III: COMPACTION PROCESSES

DRY GRANULATION OF ORGANIC POWDERS : DEPENDENCE OF PRESSURE 2D-DISTRIBUTION ON DIFFERENT PROCESS PARAMETERS.

Thibaut Lecompte1, Pierre Doremus1, Jean-Claude Le Thiesse2, Jean-Claude Masteau2, Laurent Perier-Camby3 and Gérard Thomas3 1- Laboratoire 3S, INPG, 1025 rue de la piscine, F38041 St Martin d’Hères , France 2- Rhodia, Centre de recherche de Lyon, 55 av. des frères Perret, 69190 St Fons, France 3- Laboratoire Spin, LPMG-UMR CNRS 5148, Ecole Nationale Supérieure des Mines de St Etienne,158 Cours Fauriel 42023 St Etienne, France Correspondence: [email protected]

Nowadays dry granulation of powders has become a very important research topic because dry granulation is the most economic way of granulation, making easy the particle handling, and avoiding the loss of matter during particle processing, or particle transfers. This kind of process has been deeply studied but a better knowledge appears necessary to control the great number of parameters of the process. This is particularly important in cases where the nature of the material considered may lead to compaction during which very complex phenomena can occur.

In order to try and optimise dry granulation process for organic compounds, a roll press has been realised with a series of instruments allowing the control as high as possible of the compaction process. The apparatus (figure 1) is constituted of three parts : first, a vertical container (50 kg maximum weight) with rotating steel blades avoiding arches into which the powder is poured. Then a feeder transferring the powder towards the rolls ; the feeder is equipped with an horizontal helical screw in a cylindrical draft tube (10 mm in internal diameter, 500 mm long). In the end of the feeder, a junction allows the change from the cylindrical symmetry of the feeder to the prismatic symmetry existing in the roll gap. The roll press (0 to 50000 daN, load per unit length 0 to 104 daN.cm-1) has been developed to record different major classical parameters : the roll speed, the roll gap, the press strength, the rotation angle, and the feeding rate (from 0 to 80 L min-1).

In comparison with different kinds of roll press described in literature, original instrumentation systems have been developed to catch specific data. The first one is the pressure distribution pressure profiles (radial and axial pressures) at the interface between powder and the roll wall on the roll width. Another one is the drive torque applied to the rolls. In addition a large size of smooth steel-made roll (240 mm in diameter, 50 mm width) has been chosen to make easier the extrapolation of the results to the industrial scale.


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The results obtained with an organic compound exhibit the dependence –sometimes unexpected- of the rotation angle, the feeding and the rotation speed on the pressure distribution, the roll width, and the drive torque.

The France RhôneAlpes Region is kindly acknowledged for granting funds to this research program.

COMPRESSION BEHAVIOUR OF AGGLOMERATES AND THE EVOLUTION IN TABLET STRUCTURE

Göran Alderborn Department of Pharmacy, Uppsala University, Box 580, SE-751 23 Uppsala, Sweden

An insight into the factors that control the manufacturability of agglomerates is vital for a rational approach to the problem of agglomerate engineering. In the presentation, the question of the relationship between agglomerate properties and their compression and compaction behaviour is addressed.

The dominating compression mechanisms for agglomerates seem to be permanent deformation, densification and attrition (e.g. [1]). The degree of deformation and densification that agglomerates undergo during the compression process are related to the composition of the agglomerates (e.g. [2]) but also to their physical structure, such as their size, shape and porosity (e.g. [3]). In addition, during compression of agglomerate mixtures, the relative strength of agglomerates will affect their mode of deformation [4].

By the use of relationships between the applied stress during compression and the consequent degree of compression of the agglomerate bed, an indicator of the compression mechanics of agglomerates in terms of a failure strength can be derived [5]. The failure strength can be modulated by the composition and the porosity of the agglomerates.

The response of agglomerates to the applied compressive stress will control the evolution in physical structure of the compact (e.g. [6]). The structure will possibly control a number of important pharmaceutical tablet properties, such as mechanical strength, disintegration and drug release.

In conclusion, the compression behaviour and the evolution in tablet structure during confined compression of agglomerates can be modulated and controlled by formulation factors and by agglomeration method.

1. Johansson, B., Wikberg, M., Ek, R. and Alderborn, G. Compression behaviour and compactability of microcrystalline cellulose pellets in relationship to their pore structure and mechanical properties. Int. J. Pharm., 117, 57 (1995)

2. Nicklasson, F., Johansson, B. and Alderborn, G. Tabletting behaviour of pellets of a series of porosities - a comparison between pellets of two different compositions. Eur. J. Pharm. Sci., 8, 11 (1999)

3. Johansson, B. and Alderborn, G. The effect of shape and porosity on the compression behaviour and tablet forming ability of granular materials formed from microcrystalline cellulose. Eur. J. Pharm. Biopharm. 52, 347 (2001)

4. Tunón, Å. and Alderborn, G. Granule deformation and densification during compression of binary mixtures of granules. Int. J. Pharm. 222, 65 (2001)


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5. Adams, M.J., Mullier, M.A. and Seville, J.P.K. Agglomerate strength measurement using a uniaxial confined compression test, Powder Technol. 78, 5 (1994)

6. Johansson, B., Nicklasson, F. and Alderborn, G. Effect of pellet size on degree of deformation and densification during compression and on compactability of microcrystalline cellulose pellets. Int. J. Pharm., 163, 35 (1998)

EFFECT OF PROCESS PARAMETERS ON MELT GRANULATION AND TABLET PRESSING OF PHARMACEUTICAL MATERIALS

Gavin Walker Queen’s University Belfast, School of Chemical Engineering, Belfast, UK e-mail [email protected]

In this work, lactose was granulated in a fluidised bed dryer with polyethylene glycol 6000 used as the binder. Granulation experiments were performed to assess the effect of granulation time and binder content of the feed, on the resulting granule properties such as average granule size, size distribution, granule yield stress, and granule porosity. These data were correlated using the granule growth regime model. It was found that the dominant granule growth mechanisms in the melt granulation of pharmaceutical powders were nucleation followed by steady growth. However, with high binder content the granulation mechanism moved to the "over-wet massing" regime in which discrete granule formation could not be obtained. Furthermore, the granules from the granulation process were tablet pressed using commercial equipment. The physical characteristics of the tablets were correlated with particle size, mechanical strength and PEG content of the feed granules. GRANULATION OF PHARMACEUTICAL EXCIPIENTS BY ROLL COMPACTION G. Bindhumadhavan1, J. P. K. Seville1, M. J. Adams1, R. W. Greenwood1, S. Fitzpatrick2

1- Centre for Formulation Engineering, The University of Birmingham, B15 2TT, U.K. 2- Merck Sharp & Dohme Ltd., Hertford Road, Hoddesdon, EN11 9BU, U.K. e-mail [email protected]

Roll compaction is widely used in industry to produce free flowing agglomerates from a fine particulate feed. Two of the main advantages of this process are that it is dry and continuous. Despite being superficially a simp le process, a quantitative understanding has proved difficult to develop because of the complex behaviour of particulate materials. Sub-optimal design and operation of the equipment can lead to unsatisfactory products. Johanson (1965) developed a theoretical model that enables the surface pressure, torque and separating force of the rolls to be predicted from the physical characteristics of the powder and the dimensions of the rolls. However, a detailed experimental validation of the theory has yet to be accomplished. The current paper describes such a study using an instrumented roll press and a microcrystalline cellulose powder. The measured pressure profiles in the nip region of the roll press were comparable to the calculated values. The theory was also found to predict the effect of material properties on the nip angle and the peak pressure but it was unable to account for the influence of roll speed.


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SESSION IV: GRANULE PROPERTIES THE RELATIONSHIP BETWEEN SURFACE PROPERTIES AND BINDER PERFORMANCE IN GRANULATION S.J.R. Simons1, D. Rossetti1, P. Pagliai1, R. Ward2 and S. Fitzpatrick2 1- Colloid & Surface Engineering Group, Dept. Chemical Engineering, University College London, WC1 7JE, U.K. 2- Formulation Process & Design, Merck Sharp & Dohme, Hertford Road, Hoddesdon, EN11 9BU, U.K. e-mail: [email protected]

The choice of the correct binder and wetting agent in a granulation process can critically determine the performance and stability of the resultant granules. To date, a coherent basis for making this choice has not been established, at least partly because the links between the surface properties of the solids and the interaction with the binder is not fully understood. Clearly, the surface energy of the solid particles will have an impact on the ability of binder solution to spread across the surface of the particles. The same surface energy will also influence the strength of the adhesion of the solids to the dry binder. Both factors will determine how well the particles are bound into the granule – a key determinant of solids segregation and content uniformity behaviour.

In this paper, the ability of a micromanipulator technique to differentiate between the interactions of different binders (namely, HPMC, HPC and PVP) with drug particles is reported. Differences between the powder-wetting characteristics of these binder solutions were apparent in spite of the diversity of particle sizes and shapes employed. These differences are in line with those predicted on the basis of surface energy calculations and granule properties.

BEHAVIOUR OF DRY BINDERLESS GANULES UNDER IMPACT AND DIAMETRIC COMPRESSION

Y.S. Cheong1, A.D. Salman1, A.F. Routh1, M.J. Adams2, C. Thornton2, D. K. Kafui2 and M.J. Hounslow1 1Particle Products Group, Department of Chemical and Process Engineering, University of Sheffield, Sheffield, UK. 2School of Engineering, University of Birmingham, Birmingham, UK.

Wet high shear granulation is a size enlargement process with liquid addition to convert fine powder to larger entities known as granules. However, disintegration and dispersion of these granules during application may not be effective due to the extra strength caused by the presence of binder at constituent particle contacts. The current investigation suggests that dry binderless granules may be a better option as the interparticle bonding is due to the autoadhesive effect and mechanical interlocking of the primary particles. Despite the weaker bonding, dry binderless granules can withstand considerable stress before fracture, thus enabling them to survive transportation. This work presents the mechanical behaviour of dry binderless granules, composed of monodispersed polystyrene microspheres, under different loading rates, i.e. impact and diametric compression. The method of producing dry granules with no binding agent using a high shear granulator and their strength characterisation are highlighted. Besides that, the effect of humidity on the surface interaction among the constituent particles of the granules is investigated and the influence on the macroscopic response of the granules is examined. Discrete element simulations are carried out to illustrate the evolution of damage mechanism during impact and slow compression.


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PARTICLE PROPERTIES AND ADHESIVE FORCES AS PARAMETER OF AGGLOMERATION

Karl Sommer Lehrstuhl für Maschinen- und Apparatekunde , TU München 85350, Freising Weihenstephan e-mail: [email protected]

The properties of solids are determined by their chemical composition, the disperse state, and the forces acting on the boundary surfaces. They are decisive for the behaviour of products in the manufacturing process

With decreasing particle size the forces between the particles gain in importance as compared to the particle‘s weight. Changing the adhesive forces can influence the product properties in the process and the agglomeration qualities.

Of the adhesive forces, it is the capillary force that deserves particular attention in the manufacture and application of solids. Capillary forces determine the pore structure of an agglomerated solid and the external forces brought to play during the production process. For example, if the interaction of these two effects on the pore structure is known, it is possible to influence the strength of structural agglomerates and the dissolution rate of instant products.

A constantly acting adhesive force is the van der Waals force. The name ‘van der Waals ’ is well known from our school or student days in the form of the so-called van der Waals equation of gases. The reason of this is an intermolecular attractive force due to fluctuating dipoles. This force is universal and is not identical to chemical bonds or electron bonds. The van der Waals force acts not only in gases, but also between solids, for example between the graphite layers of carbon

We all know from experience the phenomenon of electrostatic charge, which often leads to undesirable adhesive forces especially in non-conductive materials. When particles of different materials are brought into contact with one another, or are rubbed, electrons pass from one material into the other. Because the partners become oppositely charged, they also attract one another. In the case of very fine particles, electrostatic forces are an order of magnitude smaller than the van der Waals forces, and are therefore generally negligible.

The significance of the electrostatic forces is not in their magnitude, but in the fact that they have a much longer range than van der Waals forces, and can thus influence the movement of suspended particles. A classical example is the electrostatic separator, in which dust particles made over a distance of several centimetres toward the precipitation electrode. In practice, in the case of coarse particles, the distances between the particles are larger awing to surface irregularities, and the adhesive forces are thus limited. Liquid changes the system in two ways: an the one hand, "external“ forces are additionally generated by liquid menisci, while an the other hand, the van der Waals interaction is directly influenced by the presence of another substance.

If a liquid is present at the contact points, capillary forces act as a result of surface tension. Reduced pressure due to the capillary effect leads to adhesion between the two particles. The result is adhesive forces that are larger than the van der Waals forces by a factor of 5. On the other hand, the actual van der Waals interaction decreases in the presence of water by a factor of up to 100, and even by a factor of up to 5,000 with surfactants. The knowledge of the physical understanding of the adhesion forces as the bas of the agglomeration leads to practical consequences.


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AN EXPERIMENTAL STUDY OF THE IMPACT BREAKAGE OF SINGLE WET GRANULES

J.S. Fu1, A.D. Salman1, G.K. Reynolds1, M.J. Adams2 and M.J. Hounslow1

1 Department of Chemical and Process Engineering, University of Sheffield, Sheffield, UK 2 Centre for Formulation Engineering, Chemical Engineering, University of Birmingham, UK

The behaviour of wet single granules under impact loading has been investigated. They were prepared in a high-shear mixer granulator using calcium carbonate particles having different mean sizes and a range of phase volumes of a liquid binder, which was either polyethylene glycol or mixtures of glycerol and water to obtain a range of viscosities. It was found that the porosity decreased with increasing granulation time for values less than some critical time; at greater times the porosity then remained constant. A critical impact velocity was defined as the value at which a wet granule appeared visibly cracked. This quantity increased monotonically with increasing granulation time even at times greater than that corresponding to the asymptotic porosity. The critical impact velocity also decreased with increasing granule and primary particle size, exhibited a minimum value with increasing binder content and increased with increasing binder viscosity. The extent of the damage increased with increasing impact velocity following the general sequence: plastic deformation, multiple crack propagation from the plastically deformed contact region, conical-shaped debris on the target with the rebound of a cracked but coherent cap and, at greater velocities, the cap was fragmented. This behaviour corresponded to a decrease in the survival ratio and the mean fragment size with increasing impact velocity. Moreover, the size of the conical debris increased with increasing impact velocity and increasing primary particle size. In summary, an extremely detailed characterisation of the impact damage of wet granules and the dependence on their composition, porosity and loading conditions has been obtained. This should provide an improved basis for understanding the factors that control size evolution and product quality in granulation processes.

SINGLE AND BULK COMPRESSIONS OF SOFT GRANULES: DEM SIMULATION AND EXPERIMENTAL EVALUATION

A. Samimi, A. Hassanpour and M. Ghadiri Institute for Particle Science and Engineering, University of Leeds, Leeds, UK

In a number of powder processing operations such as compaction and tabletting, the behaviour of bulk powders subjected to compression is of great interest. Bulk compression of particles has been considered as a useful experimental method to characterise some properties of individual particulate solids being compressed in the bed. A large number of correlations have been developed mainly based on the experimental fittings of data to relate the applied pressure on the bed to some state of consolidation measures of powders in the bed such as bed volume, strain and relative density. Heckel’s correlation (Heckel 1961) is one of these models and is used to infer the yield stress of individual particles based on the density-pressure relationship of the bed. In spite of the extent of publications using Heckel’s model, the level of understanding of the compression mechanism as well as the identity of the parameter that is essentially characterised by the model is poor. Furthermore, there is not much detailed work investigating the bulk compression of soft granules. The most appropriate approach to evaluate this model is the combined experimental and computer simulation techniques.


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This paper addresses the deformation and failure behaviour of detergent based soft granules using uni-axial single and bulk compression methods. In particular the mechanical properties of single granule such as yield strength and Young’s modulus obtained based on single particle compression tests are used in Distinct Element Method (DEM) to simulate the bulk compression behaviour. The DEM simulations are then compared with experimental results of the bulk compression. Furthermore the identity of the Heckel parameter obtained based on the experimental and simulation is discussed.

TOWARDS A DESKTOP ATTRITION TESTER FOR SIMULATING PNEUMATIC CONVEYING G.M.H. Meesters, B. van Laarhoven and S. Schaafsma Delft University of Technology and DSM-Research

In industry solid products are sold more and more in the form of granules. Agglomerated particles in a granule form eliminate transport problems caused by sticky, hygroscopic, dusty and explosive powders. During transport of the granules they are subjected to both static and dynamic loads. The challenge is to design granules resistant to damage induced during the transport. Beekman [1] designed and developed a new test method to asses attrition tendency of small samples of granules. Pitchumani [2], improved the design to the current Crank Slider Repeated Impact Tester (henceforth CS-RIT).

In this work a comparison is made between attrition of sodium benzoate granules by pneumatic transport and attrition by CS-RIT. Sodium benzoate granules in the size range of 710 µm –1000 µm are brought in the particle chamber of the CS-RIT. The particle chamber is subjected to a linear oscillatory motion resulting in two collisions each cycle. By fixing the frequency and the amplitude of the linear oscillatory motion a fixed impact velocity is obtained. Attrition on sodium benzoate granules as function of the number of collisions is correlated to attrition induced by a pneumatic transport setup. First results will be presented.

2. W.J. Beekman, G.M.H. Meesters, B. Scarlett and T. becker. Measurement of granule attrition and fatigue in a vibrating box. Particle and Particle Systems Characterisation, 19 5-11, 2001.

3. R. Pitchumani. Breakage characteristics of particles and granules. Thesis, Delft University of Technology. 2003.

COMPUTER-AIDED DESIGN OF GRANULE MICROSTRUCTURE

Frantisek Stepanek Department of Chemical Engineering and Chemical Technology, Imperial College London, UK e-mail: [email protected]

The properties of multi-component granules depend not only on granule size and composition, but also on the spatial distribution of components within the granule. Some properties – such as the rate of release of an active component during dissolution – can be effectively controlled by the granule structure. Granule structure follows from the granulation process, but it also depends on the formulation and on the specification of the raw materials (e.g., primary particle size distribution). Microstructure design thus brings together formulation design and process design. In this contribution we will present computational methods for “virtual granulation” which enable


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the construction of realistic three-dimensional models of granules formed by the agglomeration of primary particles of defined size, shape and surface properties, with binder droplets of defined spreading and solidification rate. As a post-processing step, a software module for “virtual dissolution” enables the release profiles of individual components from each designed granule to be determined. The overall design methodology, which involves finding the inverse of computationally determined structure and property functions, will also be presented.

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