guide to extrusion

A practical guide to the extrusion andspheronization of pharmaceuticals usingNICA™ System

Aeromatic-Fielder

by Mike Waldron

Extrusion and Spheronization of pharmaceuticals using NICA™ System -

TechPapers/NICA/09.02.2001-GB

Contents

1.0 INTRODUCTION2.0 MIXERS

2.1 PLANETARY2.2 HIGH SHEAR2.3 CONTINUOUS2.4 MIXING FOR EXTRUSION

3.0 EXTRUDERS3.1 THE RAM EXTRUDER3.2 THE SCREW EXTRUDER3.3 THE GRAVITY FED EXTRUDER3.4 THE NICA SYSTEM EXTRUDER

4.0 SPHERONIZERS5.0 FORMULATION

5.1 MICRO CRYSTALLINE CELLULOSE (MCC)5.2 BINDERS (as an aid to Extrusion)

6.0 EXTRUSION AND SPHERONIZING USING NICA SYSTEM6.1 MIXING

6.1.1 Judging the Wet Mass6.2 EXTRUSION in the NICA E140

6.2.1 Set-Up6.2.2 Testing the Wet Mass6.2.3 Reducing Extruder Load6.2.4 Judging the Quality of Extrusions6.2.5 “Sharkskin” or “Sawtooth” Extrusions6.2.6 Screen selection6.2.7 Optimization of Extrusion

6.3 SPHERONIZATION6.3.1 Principles Affecting Pellet Quality6.3.2 Operating the Spheronizer6.3.3 The Mechanism of Pellet Formulation

6.4 OPTIMIZATION6.4.1 Repeat Processing

7.0 INTEGRATED PRODUCTION PLANTS



1.0 Introduction

The production of pellets by Extrusion and Spheronization involves three essential processes:

- Mixing of the dry powder components with a liquid to form a homogeneous and evenly wetted mass

- Extrusion of the wet mass into cylindrical “spaghetti like” strands and finally

- Spheronization which fragments the strands into short cylindrical lengths and roll-forms them into spheres.

Equipment for all three processes are available from several manufacturers and, in the case of Mixersand Extruders, in a number of different forms. This guide will first describe and categorise the basicequipment types available and then give practical guidance on the use of Aeromatic-FielderNICA System.

2.0 MixersThere are three general types of mixer typically used in pharmaceutical production of pellets: Plan-etary, High Shear and Continuous. All produce suitable wet mass for feeding extruders and so thechoice is non-critical on small or laboratory scale. In a production environment however, the practi-cality of handling and feeding materials favour the High Shear or the NICA Continuous Mixer.

2.1 Planetary MixersPlanetary Mixers originated in the bakery and food processing Industries and provide for dry mixingand wetting of the charge. The low intensity work input leads to long processes of typically 30 min-utes. Discharge is generally effected by tipping or scooping from the bowl which is far from ideal inlarge scale operations for feeding an extruder.



2.2 High Shear Mixers

With 10 to 15 minutes processing times the High Shear mixers have generally supplanted planetarymixers in pharmaceutical production. Shortened processing times are achieved by higher toolspeeds, the generation of shear rather than kneading action in the product and the provision of a“chopper” for size reduction of agglomerates and to assist in the fast and even distribution of liq-uid. The high intensity of mixing makes practical the use of liquid spray systems which also assists inspeeding up the process.

Discharge is typically through a side mounted valve. Using a variable speed impeller linked to levelcontrol in the Extruder hopper, enables a High Shear mixer to be directly coupled. However, theneed to empty the High Shear before loading the next batch of dry powder requires the Extrusion/Spheronization process to be temporarily halted.

2.3 Continuous Mixers

Continuous mixing of wet mass is not commonly used in Pharmaceutical Production because suchequipment tends to be large scale and to have inherent start-up and shut-down losses of material.Consequently, with the relatively small scale production volumes in Pharmaceuticals and the highvalue of many ingredients, continuous mixing is not seen as economic.

2.3.1 NICA M6

The NICA System Continuous Mixer has been down sized to an output of 2 to 6 kg/minute and atthis size is ideally suited to feeding the larger production scale extruders. Moreover, the mixingprocess is not only continuous but effectively instant and without start-up and shut-down losses; itcan therefore be run upon demand to supply the downstream processes. There are no scale-upissues because irrespective of run-time the mixing conditions remain the same.

Finally, the production of wet mass upon demand for the Extruder means that there is a minimum ofproduct in process and the delay between mixing and extrusion is constant - a useful characteristic ifthe mechanical properties of the wet mass change with time.

The NICA mixer can be arranged to discharge directly into the extruder hopper giving a compactinstallation; however, as the mixer cannot perform dry blending of the powders, this has to becarried as a separate operation after the dispensary - usually by tumbling of the bulk containerbefore loading onto the Mixer.



2.4 Mixing for Extrusion

Wet mixers in the Pharmaceutical Industry are most generally used to produce granules for dryingand subsequent tablet compression. Tabletting formulations are created specifically for this purposeand generally require a high work input to bind the powders together and build the granules.

For extrusion the formulation requirements are different; a robust granule is not required andshould not be sought. Extrusion formulations tend to be wetter (20-40% LOD) than those of granu-lation (10-20% LOD) because of the excipient components used and the need for the wet mass topass through a screen. Extrusion formulations require even wetting without high work input ormassing. The mixing regime should be constructed with these principles in mind.



3.0 EXTRUDERSTo produce an extrusion the wet mass has to be raised to a pressure sufficient for it to undergo plasticdeformation and flow through a die (the cylindrical hole of the extruder screen). If this were theonly requirement the process would be simple - requiring high levels of moisture and low pressures.However, the subsequent Spheronization process requires the extrusion to be friable enough to breakinto short lengths, sufficiently plastic for these short lengths to form into spheres and not so wet thatthe spheres agglomerate and become oversize. These are conflicting requirements which are ren-dered compatible by careful formulation and by choice of suitable characteristics in the Extruder.

3.1 The Ram Extruder

This simplest form of extruder, commonly used for academic study, is made from a piston running in abarrel with a single or multiple holed die at the discharge end. Pressure is produced with a minimumof shear work and certain formulation characteristics are easily studied. A minimum pressure must begenerated before extrusion begins, (or can be maintained). Extrusion is continuous at this pressureuntil the Ram is nearly empty, at which point pressure has to rise because of complex flow patternsset-up as the piston face approaches the die plate. As a production tool, other than for very smallquantities, the Ram extruder is of no practical value.

3.2 The Screw Extruder

Screw extruders have been used for many years in the plastics, rubber and food industries and havebeen adopted into pharmaceutical use.

Shear work is put into the wet mass as the screw rotates in the barrel. A pressure gradient is set-upalong the length of the barrel and when the minimum extrusion pressure is reached at the die endextrusion begins, the process is continuous if the inlet end is kept supplied with wet mass.

Twin screw extruders can have kneading and mixing sections fitted at the feed end so that wettingcan be carried out in the barrel - however, this facility is rarely used due to the difficulty of optimizingthe two processes when they are performed at a common speed.

Work input and high temperature rise tends to be high in screw extruders due to the length of barreland shear work input required to generate the required pressures. This can lead to moisture gradi-ents in the barrel as liquid migrates towards the low pressure end. In extreme cases this can causeseizure after a period of operation if the moisture loss severely effects the rheology of the product inthe barrel.

To control heat gain the extruder barrel can be water cooled. Throughput can be increased by replac-ing the normal flat axial screen on the barrel end with domed or cylindrical screens. Finally the dis-charged extrusions are easily collected for batching into a Spheronizer.



3.3 The Gravity Fed Extruder

In this design the product is gravity fed into two hollow, meshing, gears. The die is formed by drill-ing holes between the gear teeth through to the hollow bore.

As the gears rotate each gear tooth enters the gap between the two opposite teeth producing aform of piston (ram type) action and pressurises the product through the die. It is not possible toproduce a true “ram extruder” effect due to the imperfect fit of the gear teeth which results inleakage both around the flanks and ends of the teeth. Consequently, there is a significant degree ofshear work input and throughput is low.

The extrusions fall into the bore of each gear wheel and these are set at an incline to assist dis-charge. The more plastic or sticky materials tend to cause blockages. Finally, to alter the die lengthor diameter involves changing the gear wheels which are costly components. In a similar design thegears are replaced by cylinders, one of which is hollow and drilled radially to form the dies. Similarcomments apply as for the gear extruder.

Different Extruder types

Screw Extruders

Axial Radial

Gear Cylinder

Gravity fed Extruders



3.4 The NICA System Extruder

The design employs two rotors counter rotating within a cylindrical screen. Wet mass is gravity fedonto the feeder which controls the rate of product delivered to the Impeller which in turn forces theproduct through the screen.

The essential characteristic is that shear work is only carried out on a small volume of product directlyprior to extrusion. Work input is minimised and the design does not suffer from moisture gradient.Screen area is large in comparison to other similar sized extruders and so throughput correspondinglyhigh. Extrudate quality and that of resultant pellets is generally un-effected by the rate of extrusion.

The degree of compression of the extruded product is controlled by the choice of screen. Manysimple formulations can be successfully proceeded through screens with a Diameter/Length ratio of1:1. More difficult formulations give improved results through thicker screens of D/L Ratio of up to1:1.5.

The NICA extruder can be run with a flooded inlet in which case throughput is governed by the ex-truder speed, or at “starvation” in which case throughput is governed by the upstream mixing proc-ess. This latter case is the preferred option when linking the Extruder to the NICA Continuous Mixer.

Operating principle of the NICA ExtruderProduct being fed

Product being pressurisedand Extruded

Extrudate

Perforated screen



4.0 SPHERONIZERSIn general Spheronizer design consists of a wheel with a friction pattern machined on its top surfaceand spinning on a vertical axis within a parallel sided bowl. Both wheel and bowl are usually con-structed in stainless steel, although coatings are sometimes used to reduce the tendency of someproducts to stick.

Wet extrusions are dropped onto the spinning wheel which fragments them and throws themagainst the bowl wall. The forming pellets are decelerated by friction against the wall and dropdown onto the wheel which accelerates them again so that the process continues. This results in a“rope” of product circulating around the bowl and the constant rolling action between bowl wall,pellets and wheel gradually forms the pellets into spheres. Wheel speed is variable about a typical10 metres per second peripheral speed.

The essential design is common between different manufacturers so it remains only to point out theparticular features of the NICA System Spheronizer:-

a) Smooth Edged Wheel - this patented feature adds a smooth chamfered edge tothe friction wheel rim. Circulating pellets, which must make the transition between themoving friction surface and the stationary bowl wall, thus avoid the milling action ofbeing caught by friction pattern against the bowl wall.

b) Interchangeable Friction Patterns - the smooth edge rotor can take differentfriction pattern inserts including Radial and Rectangular Cross Hatch Patterns.

c) Close Fitting Wheel/Slit Air - the radial clearance (slit) between wheel and bowl isonly 0.15 to 0.3 mm which, together with the smooth edge, results in only smallamounts of dust falling beneath the wheel. In this way the provision for slit air needonly be used when it is required as an aid to spheronizing (to reduce moisture build upand particle agglomeration) and not to control the loss of product beneath the wheel.

d) Controlled Discharge - the product discharge design produces a controlled streamof pellets which facilitates the subsequent pneumatic conveying of pellets into thedryer.



5.0 FORMULATIONThe conflicting requirements of the extrusion and spheronization processes as regards the propertiesof the wet mass have been discussed in Section 2. Although the principle of operation of the ex-truder can help minimise the effects of moisture gradients and excessive work input it remainsfundamental to the success of the process that the formulation imparts suitable properties to thewet mass.

In rare cases the properties of the active compound in conjunction with typical excipients such asLactose or Dicalcium Phosphate will produce acceptable pellets but this is generally a strong compro-mise resulting from formulation constraints.

5.1 Micro Crystalline Cellulose (MCC)

In the great majority of cases the formation of pellets is greatly facilitated by the presence of 20%or more of Micro Crystalline Cellulose in the dry weight of the formulation. MCC has been widelystudied and is the subject of continual development by the FMC Corporation in the USA amongothers. Two FMC grades are commonly used in extrusion/spheronization, these being Avicel PH101and PH102. These and other grades are also essential components of pelletization formulations forHigh Shear and Rotary Processor techniques.

This Guide will not attempt to fully explain the action of MCC which is covered by numerous publi-cations. However, the structure if MCC is essentially fibrous and highly porous and is able to absorblarge quantities of solvent before becoming fully wetted. When under compression some of thismoisture can be liberated and become available to plasticise the wet mass and permit it to flowthrough the die. On the die exit the pressure is released and the free solvent re-absorbed, returningthe extrudate to its earlier “stiffer” state.

Once in the Spheronizer the MCC performs a second time. The extrusions fragment on impact withthe wheel but are then repeatedly compressed between the bowl wall and other pellets as theycirculate. A further densification of the product takes place and solvent is squeezed out of the struc-ture first providing the required plasticity and then evaporating from the pellet surface to leave astable entity not prone to further growth. It is the high solvent absorption of MCC in extrusionformulations which leads to their high solvent capacity compared to normal Granulation formula-tions. (ref: 2.4)

The presence of MCC also generates a degree of buffer in the formulation making the process morestable against the normal fluctuations in solvent content. If under wet however MCC will not releasesufficient solvent and will result in high extruder loads.

The triangular illustrations attached in Figures 1 and 2 show the performance envelope of the NICAE140 Extruder operating on two formulation models. Figure 1 shows a “Soluble Active” modelcomprising ß-Lactose, Avicel PH101 and Water and using Ø 1.0 x 1.0 mm thick screens with



Punched, Drilled and conical drilled Profile screens (re: 6.2.6). Figure 2 shows an “Insoluble Ac-tive” model with Dicalcium Phosphate, Avicel PH101 and Water. These diagrams represent theproportions of each component in the wet mix. Correcting to dry weight it can be seen that with theappropriate choice of screen the MCC content in the Soluble model can be as low as 10% and in theInsoluble model 30%.

Soluble active model in NICA E140 (fig.1)Nominal screen dimensions Ø 1.0 x 1.0 mm

B-LactoseB-Lactose B-Lactose

Water WaterWater

AvicelPunched Screen

AvicelDrilled Screen

AvicelProfile Screen

Non-soluble active model in NICA E140 (fig.2.)Nominal screen dimensions Ø 1.0 x 1.0 mm

Water Water Water

AvicelPunched Screen

AvicelDrilled Screen

AvicelProfile Screen

DicalciumPhosphate

DicalciumPhosphate

DicalciumPhosphate

5.2 Binders (as an aid to Extrusion)

Although normally used in granulation formulations some binders, in small quantities, have beenfound useful in assisting the extrusion of difficult formulations. The operating mechanism appearsto be as a form of die wall lubricant and a general aid to plasticity of the wet mass.

Hydroxy Propyl Methyl Cellulose (HPMC), at a dry weight concentration of 1 to 2% and using lowerviscosity grades, has been successfully used in both soluble and insoluble active formulations wherethe MCC content was lower though ideal. In a particular example, with an almost insoluble activecontent at 85%, extrusion and spheronization were successful with 14% MCC and 1% HPMC.



6.0 EXTRUSION AND SPHERONIZING USING NICA SYSTEMDevelopment of a successful process depends primarily upon a viable formulation and then upon thecorrect choice of Mixing Extrusion and Spheronization parameters.

The essential requirements are: -

a) Mixing - the product should be evenly wetted but not over-massed

b) Extrusion - the extrusion should be cylindrical and should break under its ownweight at typically 20 to 50 mm in length. (larger lengths can work)

c) Spheronization - the extrusion should fragment into short cylindrical lengths, produce a full roping action in the bowl and should form round pellets in 2 to 4 minutes.

We can expand upon these requirements as follows: -

6.1 Mixing

Planetary mixers can be run at normal granulating speeds.

High Shear mixers are frequently best run at low speeds to avoid over massing of the product. Oncethe product is wetted there is no need for further mixing.

The NICA Continuous Mixer is generally run at 2 to 4 kg min. with the standard 2,800 rpm mixingwheel speed and an open discharge orifice. There should be only 2 to 4°C product temperature riseand a low, steady, motor load.

6.1.1 Judging the wet mass

When wet the average formulation will form an easily compacted solid ball in the hand. When asmaller quantity is squeezed (compressed and sheared) between thumb and forefinger, the productshould be found to “glide” - in effect, it becomes plastic under pressure. This simple demonstrationand check shows that the Avicel is sufficiently wetted to perform its main function.



6.2.Extrusion in NICA E140

6.2.1 Set-Up

Fit a Punched screen into the extruder with hole diameter just below the required mean particlesize (e.g. a Ø 1.0 mm screen will usually give a mean particle diameter around 1.1 mm).

Set the feeder and impeller speeds at 1/3 to 1/2 of the full speed (E140, 60F/50I, E220 45F/40I) andnote the no-load currents.

6.2.2 Testing the Wet Mass

Bring the wet mass up to a consistency where the “glide” referred to in 6.1.1 is just evident and feeda small quantity into the extruder (E140 300 gms., E220 600 gms.). Observe the effect upon impellermotor amps which should remain below 90% of full load current. Examine the extrusions producedfor cylindricity and length. If they are cylindrical and under 100mm long proceed to section 6.2.5.

If they are not cylindrical or are very short, or if the motor current rises to the full load current ofthe impeller motor it indicates that more wetting is required.

6.2.3 Reducing Extruder Load

If the Extruder is producing cylindrical extrusions, 20 to 50mm long, but the Impeller motor loadremains non-sustainable it can be reduced in two ways:-

First - reduce the feeder speed. This reduces the rate of product feed to the Impeller and hence itsload. If a drop of 10 rpm on the feeder has negligible effect then:-

Secondly - lower Impeller and Feeder speed together in 10 rpm steps. This effectively lowers thegearing on a variator driven machine while calling for a lower power input to the two rotors.

NICA System E140 ExtruderVariation of throughput withfeeder speed (typical)

Screen Ø 1.0 x 1.0 mmImpeller Speed

40 rpm

50 rpm

60 rpm

0.5

0.6

0.7

0.8

0.9

1.0

1.1

45 90 135

Feeder Speed / rpm

Th

rou

gh

pu

t (k

g/m

in)



6.2.4 Judging the Quality of Extrusions

The most important observation to make is to check that the Extruder is producing full cylinders(that is, that the die is filled) which do not hang in long strands and stick together.

QUICK CHECK :- Take about 10 grams of extrusions and shake between cupped hands. If the breakinto short lengths (less than 10 mm) and do not stick together there is every chance that they willspheronize.

6.2.5 “Sharkskinning or Sawtooth” Extrusions

In many cases the surface of an extrusion may be seen to have a regular circumferential ribbingresembling a saw-tooth pattern - also very commonly referred to as “Sharkskin”. Even when notvisible to the naked eye it may be present when viewed under low power magnification. This is anatural die- exit effect and is quite normal.

It is common (and wholly unnecessary) for workers in the field to spend considerable timeeradicating this effect - usually by using expensive long die-length screens. Not only will this reducethroughput and raise processing temperatures but the dense and smooth extrusion produced is lesslikely to fragment into short lengths and will be slow to round into spheres.

The ribbing effect may be argued to aid fragmentation by introducing weak spots and they are selfevidently absent in the final pellet. There is no evidence to suggest that they produce dust -provided the mass is sufficiently wet when extruded.

Sharkskinning should not be confused with incomplete die-filling (when the extrusion does not forma cylinder of regular cross section). This is undesirable and is unlikely to produce good pellets oftight particle size distribution. This problem is best solved by choice of a different screen or, inextreme cases, by formulation changes.



6.2.6 Screen SelectionIf the Extruder is not over-working and the extrusion remains as incomplete cylinders there is astrong likelihood that a Drilled or Profile Screen will be required.

NICA Extruder hole shapes

The correct selection of extrusion screen is fundamental to achieving the required particle size,quality and size distribution and screen selection becomes an iterative process along with wet masswater content and spheronization. However, the essential screen characteristics are known andsummarised below together with listings of the standard screen sizes available.

A. Punched ScreensThe following screens are standard stock items:

Ø 0.6 x 0.5Ø 0.8 x 0.7Ø 1.0 x 1.0Ø 1.2 x 1.2Ø 1.5 x 1.5

All screens are manufactured in AISI 316 stainless steel.

Punched holes Conventionally drilled holes Profile (conically)drilled holes

Ø < tØ > t(Manufacturing limitation)

Ø > tIn special cases Ø < t



Specially manufactured screens can be offered with hole sizes greater than 1.5mm - typically 2.0,2.5 and 3.0mm. We cannot offer non-standard screens with hole sizes smaller than 1.5mm.

The defining criteria on punched screens is that the screen thickness can be no greater than the holediameter, due to the practical difficulties of punching holes. Below 1mm the screen thickness mustbe less than the hole diameter. This limitation on thickness, together with the fact that punchedholes are not perfectly cylindrical, puts a limit on the amount of compression that can be put intothe product and the quality of the resulting extrudate. Consequently, best extrusion results are notobtained with punched screens. However, because they are relatively inexpensive to make in seriesand because sufficiently good results can be obtained with most well-formulated prod-ucts, they are the first choice where they can be used.

B. Profile ScreensThe following screens are standard sizes but are not held in stock.

B.1 Profile screens - standard hole density (same as punched screens) in:

Ø 0.8 x 0.7 P 'P' = Profile Ø 1.0 x 1.0 P Ø 1.2 x 1.2 P Ø 1.5 x 1.5 P

B.2 Profile screens - high hole density:

Ø 0.8 x 0.7 P.HD 'HD' = High Density Ø 1.0 x 1.0 P.HD Ø 1.2 x 1.2 P.HD Ø 1.5 x 1.5 P.HD

These screens are manufactured from AISI 316 stainless steel.

Profile screens have conical drilled holes arranged such that the hole converges in the direction offlow. This provides a greater degree of compaction over punched screens, and ensures completedie-fill. Typical benefits from using profile screens are a tighter particle size distribution in the finalpellets and less sensitivity to variations in moisture content. However, with the standard hole den-sity the through-put will be reduced and the extrusion temperature higher than with the equivalentpunched screens. The high density screens, with a greater open area, largely redress the balance,but are more expensive and less robust.



B.3 Profile Screens - Small Hole Sizes

The following screens are standard sizes but are not stocked:

Ø 0.6 x 0.6 P Ø 0.6 x 0.5 P Ø 0.5 x 0.6 P Ø 0.5 x 0.5 P

These screens are manufactured from hardened 304 stainless steel.

We use 316 stainless steel for the majority of screens because of its generally acceptedpharmaceutical compatibility. However, at small holes sizes, its poor mechanical properties make thescreens fragile. It is possible to drill (but not punch) holes in hardened 304 stainless steel and thesescreens have now found pharmaceutical applications where 304 stainless steel has been consideredacceptable.

B.4 Special Profile Screens

The above size ranges are designed to match the great majority of user requirements. Screens withnon-standard hole diameters and thicknesses can be made with no particular limitation on choiceother than the subsequent cost of manufacture. We recommend that before any special screens arecontemplated, it should be clearly established that the mechanism of sphere formation follows theclassical route, that is, that cylindrical extrusions fragment into short cylinders which then roll intospheres of mean diameter equivalent to or slightly larger than the screen hole size (ref: 6.3.3). If thisis not the case, then the results obtained from the specially manufactured screen may be quiteunpredictable.

C. Drilled Screens

Conventionally drilled screens (parallel sided holes) have effectively been superseded by Profilescreens. Such screens used to be made with thickness greater than diameter (typically 1.5 or 2mmthick for a Ø1mm hole) in order to give additional compaction and improved die filling. They wereexpensive and gave poor throughput. However, special screens are manufactured where requested,particularly to match existing screens currently in use.



6.2.7 Optimization of Extrusion

Having produced a cylindrical extrusion at a sustainable Impeller load any other adjustments foroptimization must depend upon results in the Spheronizer. Optimization will be an iterative processbetween Extrusion and Spheronization.

6.3 Spheronization

6.3.1 Principle variables affecting Pellet Quality

Given a viable formulation, pellet quality depends upon the following three variables:-

Load-Too little and the pellets loose the interactive forces which help them to round.-Too much and the roping action will be lost and too much work put into a smallproportion of the load - pellet quality suffers.

Speed-Too fast and the Spheronizer will create dust (if the extrusions are too wet theforming pellets may agglomerate or stick to the wheel)-Too slow and the process will take longer than necessary or the pellets not achieveroundness.

Time-Too short and the pellets will not be round-Too long and the pellets may grow too large or dry out resulting in dusting orbreakage of some pellets. Whether or not pellet equality suffers the production rate isreduced.

However, with a robust formulation any one of these three parameters may be varied 25% or morewithout serious effect. Good spheronization is a very stable process.



6.3.2 Operating the Spheronizer

The batch load should be dropped onto a spinning Spheronizer wheel.

Use the following basic set-up for the initial trial:-

Once in the bowl observe the roping action and see that all the material is circulating - there shouldnot be a stagnant ring of product on the top of the rope. If the roping action is poor a small amountof product may be discharged with the Spheronizer running or the wheel speed increased 20%. Ifthe problem is not remedied by these means a baffle may be placed against the bowl side to deflectthe top of the rope into the centre.

Model S320 S450 S700

Load/grams 1000 2000 6000

Speed/rpm 600 450 300

NICA Spheronizer - Optional product deflector

Stagnant MaterialHeight adjust defectordiverts stagnant materialinto the centre

Circulating Rope



6.3.3 The Mechanism of Pellet Formation

On early spheronization runs take small samples of pellets immediately after loading and at 30second intervals. Examine them under a magnifying glass and observe the mechanism of pelletformation.

The extrusions should fragment into short cylinders which then roll into spheres in under four min-utes. If the extrusions fragment into non-cylindrical particles of wide particle size distribution theprocess will take longer than necessary and may result in a wider than necessary pellet size distribu-tion, there will also be a danger of sticking to the bowl walls.

Moisture Content

If the extrusion fragments to short cylinders which then grow oversize the mix is too wet. If theyfragment into small particles they are too dry.

If the extrusions fragment to non-cylindrical pieces which then grow oversize the mix is too wet butwill also require a change of extruder screen to improve the extrusions. If the pieces will not formpellets and begin to dust the mix will require more wetting and possibly a change of screen.

Mechanisms for sphere formation

Poorly formedExtrusions

fragment and build spheresslowly

Well formedExtrusions

break intoshort lengths

and round quickly



6.4 Optimization

Obtaining the roundest spheres with the narrowest particle size distribution is a question of findingthe best balance between

1. Mixer - Moisture content of the Wet Mass - must be wet enough to extrude but not so wetthat there is uncontrolled pellet growth in the Spheronizer

2. Extruder Screen Selection - which must provide cylindrical extrusions which fragment toregular short lengths and are not so dense that they will not round in the Spheronizer. There is aclear link between the moisture content of the wet mass and the work input during extrusion -which in turn is affected by screen hole diameter and thickness. If the work input is higher, thecompaction will be increased.

3. Spheronizer Load/Speed/Time - all three parameters can be used and balanced to give therequired work input to achieve roundness (already described in section 6.3.1).

Typical effect on particle sizedistribution of moving frompunched to profile screen (Ø1.0 x1.0 screen Lactose Avicel placebo)

0

20

40

60

80

0 500 630 710 800 900 1000 1120 1250 1400

Mesh Size (µ)

Punched Screen

0

20

40

60

80

0 500 630 710 800 900 1000 1120 1250 1400

Mesh Size (µ)

Profile Screen

Weigh

t (%)

Weigh

t (%)



6.4.1 Repeat Processing

Although much can be learnt from mixing/extruding/spheronizing small individual lots it will even-tually become necessary to try a longer extrusion and repeated spheronization. To match the pro-duction environment the Extruder needs to be allowed to reach its equilibrium temperature. Like-wise, the Spheronizer will take several successive sub-batches to reach its equilibrium conditions ofmoisture (within the bowl) and machine temperature.

In practice there are two significant effects: -

1. Pellet GrowthThe particle size distribution tends to rise slightly (less than a sieve fraction of themean) during the first two or three sub-batches.

2. Product Build UpThere may be a tendency for product to build up on the friction wheel.

Both these conditions indicate the need to reduce moisture content by (usually) ½ to 1% in the wetmass. If pellet growth remains a problem (because of increased load in the Extruder due to moisturereduction), then small amounts of purge air can be used (increments of 0.1 bar) to provide a degreeof drying in the Spheronizer and consequent stabilization of the pellets.

Best results are obtained when Spheronizer parameters are chosen such that variations of oneminute of spheronization time about the mean make little difference to mean pellet size. Theprocess is then stable.

NICA System temperature rise in processMixer2-8ºC

Extruder2-30ºC

Spheronizer2-6ºC

- Main heat gain is from the extruder

- The plant takes time to reachequilibrium (may be preheated)

- Pellet size distribution starts smallthen stabilises after about threecycles

- Vapour extraction is necessary toavoid heavy condensation



7.0 Integrated Production PlantsPelletizing plants can be constructed in a variety of ways to produce the desired output. The tablebelow gives the approximate capacities of the different equipment in the range.

• Equipment Capacities

Mixer

M62 - 6 kg/min

E140 Extruders E2000.5 - 2.0 kg/min 2.0 - 8.0 kg/min

Spheronizers

S320 S450 S7000.2 - 1.0 kg 0.4 - 2.0 kg 2.0 - 10 kg

2 - 6 minute cycle

The heart of any system is the extruder/spheronizer combination. Since the spheronization cycle isusually the rate limiting step in the cycle it is common to link one extruder to two spheronizersthrough a shuttle box. The following table gives approximate plant capacities.

• Combined Units

- Pilot

- Small

- Intermediate

- Large

E140/S450

E140/Two x S450

E220/Two x S450E220/S700

E220/Two x S700

30kg/hr }

60kg/hr }

60kg/hr }90kg/hr }

180kg/hr }

SCALE EQUIPMENTTYPICAL PRODUCTION

OF WET PELLETS

Sometimesless, oftenup to twiceas much



The Pilot and Small Scale Plants are illustrated blow showing a collector/dumper for the single sphe-ronizer and shuttlebox for the twin spheronizer.

NICA System E140 / S450 pilot scale plant

E140 / 2 x S450 small scale plant

Spheronizers movedforward to give access forcleaning maintenance

Shuttle box

S450

E140

S450



Fully integrated plants can be built with the feed of wet mass from either batch or continuous mix-ers. The use of a continuous mixer brings the significant advantage that plant throughput is set atthe output of the mixer with the downstream extrusion running at starvation; this avoids complexdischarging cycles from a batch mixer and downtime while it is reloaded and the wetting processrepeated.

One or more batch driers can be used with each receiving a certain number of spheronizer sub-lotsbefore raising the drying temperature to complete the cycle. Continuous driers may be used as analternative to batch units.

A complete pelletizing plant is illustrated in the diagram below



Bulk materials are sieved and weighed into a batch sized container which passes to a tumbler for drymixing. The bulk container is lifted and positioned over a NICA M6 continuous mixer which feeds anextruder/spheronizer combination. Wet pellets are air conveyed into a batch dryer. When dry thepellets are sieved again with the useable fraction passing to a tablet coater.

Integrated Pelletizing PlantNICA M6 Mixer / E220 Extruder / S700 Spheronizer / Size 6 Fluid bed dryer with CIP

Feed Bin

Pump

Tank

Extruder

Mixer

Collector/Dumper

Spheroniser

Fluid Bed Dryer

Exhaust air

Air

Product

E220

S700

Water treatment unitSteam

PotableWater

REV. OS.Water

Screw Feeder

Feed

guide to extrusion

Documents

full load

standard hole

soluble active

high work

particle size

high shear

gravity fed

short cylindrical