spray rates were found to be stronger and contained fewer fi nes. The same effect could be seen in the particle size distribution. The amount of fi nes could be reduced by increasing the spray rate (Figure 7).Interestingly, even though PVP K90 formed the strongest agglomer-ates under all test conditions, PVA-PEG led to a much more homoge-neous particle size distribution. As soon as high spray rates were set, more than 90 % of the formed agglomerates obtained a particle size of 125–355 µm.

0

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16 21 26 16 21 26 16 21 26

PVP K25 PVP K90 PVA-PEG

Binder / spray rate [g/min]

Res

idua

l fin

es /

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bilit

y [%

]

Residual fines Friability

Figure 6: Fines and friability after 3 minutes testing time as function of spray rate and type of binder

0.0

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16 21 26 16 21 26 16 21 26

PVP K25 PVP K90 PVA-PEG

Binder / spray rate [g/min]

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icle

siz

e di

strib

utio

n [-]

<125µm 125-355µm >355µm

Figure 7: Particle size distribution as function of spray rate and type of binder

All agglomerates could be compressed into strong tablets, whereas the strongest were the ones containing PVA-PEG graft copolymer. Presumably, this is due to the fact that this polymer is offering elastic as well as plastic deformation.

0

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16 21 26 16 21 26 16 21 26

PVP K25 PVP K90 PVA-PEG

Binder / spray rate [g/min]

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ile s

tren

gth

[N/m

m²]

Figure 8: Tensile strength of tablets

ConclusionViscosity of the polymer solution plays a decisive role in wet granulation processes. It infl uences wetting behaviour and drying time and therefore is decisive in infl uencing the proper-ties of the fi nal granules.PVA-PEG graft copolymer was found to be an interesting alter-native to the standard PVP grades – effi cient and easy-to-use. The resulting granules offer a very narrow PSD. As soon as high spray rates were applied, more than 90% of the agglom-erates were found in the particle size class of 125–355 µm. Furthermore, these particles obtained excellent compressibil-ity resulting in tablets of high hardness.The peroxide free PVA-PEG copolymer is an effi cient binder combining low viscosity of the polymer solution and strength of the fi nal agglomerates which in turn led to high tablets hardness.

References[1] Kolter, K.; Binding properties of the new polymer Kollicoat® IR;

AAPS Annual Meeting and Exposition; Nov. 10–14, 2002; Toronto, Canada

[2] Bühler, V.; Kollidon® Polyvinylpyrrolidone excipients for the phar-maceutical industry; 9th edition; 2008; BASF SE, Ludwigshafen, Germany

[3] Agnese, T.; Mittwollen, J.-P.; Kolter, K.; Herting, M. G.; An Innova-tive Method to Determine the Strength of Granules; AAPS An-nual Meeting and Exposition; Nov. 16–20, 2008; Atlanta, Georgia, U.S.A.

PurposePVA-PEG graft copolymer is originally intended for instant release fi lm coating applications. However, the polymer offers excellent wet bind-ing properties as well. Since this synthetic polymer is peroxide-free, it can be considered as binder for actives being vulnerable to oxidation [1].

To evaluate the wet granulation properties of PVA-PEG, the fi ndings were compared to those of polyvinylpyrrolidone (PVP) which can be considered as standard binding agent. Different grades are available, varying in molecular weight, viscosity and K-value respectively. Typi-cal wet binders are PVP K25, K30 and K90. With regard to most of their properties, K25 and K30 were found to be almost equal, whereas K90 differs distinctively in regard to binding capabilities and viscosity of its aqueous solutions [2].

The aim of this work was to compare the wet binding properties of PVA-PEG graft copolymer and the PVP grades K25 and K90 in a fl uid bed granulation process.

Materials and MethodsMaterialsAs wet binders, the PVP grades K25 (Kollidon® 25), K90 (Kollidon® 90F) and PVA-PEG graft copolymer (Kollicoat® IR) were tested. All three products are supplied by BASF SE, Ludwigshafen, Germany. As fi lling material, a special lactose grade for wet granulation (Granu-Lac® 200, Molkerei Meggle GmbH & Co. KG, Wasserburg, Germany) was used.

MethodsThe granulation process was performed according to the schema shown in Table 1.

Batch sizeInlet air quantityInlet air temperatureProcess timeSpray rate

1,150 g85–110 m3/h60 °C45 min16, 21, 26 g/min

Table 1: Schema of the trial set-up

The binders were applied as aqueous solutions, leading to a polymer content of 5.0 % in the fi nal granules. Of all granules, particle size dis-tribution and friability were determined. Eventually, the granules were compressed to tablets applying a compression force of 15 kN.

ViscosityIn order to test the rheological investigations on dynamic viscosity, the Thermo Scientifi c HAAKE RotoVisco 1 rotational rheometer (Thermo Fisher Scientifi c, Karlsruhe, Germany) with liquid temperature control for concentric cylinder measuring geometries was used.

GranulationAs fl uid bed granulator, the GPCG 3 (Glatt GmbH, Binzen, Ger-many) assembled with 5 L product container and top spray nozzle (d = 0.8 mm) was used.

Particle size distributionThe test was performed with a sieve tower Retsch AS 200 (Retsch GmbH, Haan, Germany) by using sieves in the range of 38–500 µm (according to Ph. Eur.). The results were categorised into three differ-ent particle size classes: coarse (> 355 µm), mean (125–355 µm) and fi ne (< 125 µm) particles.

FriabilityAn air jet sieve LPS 200 (Rhewum GmbH, Remscheid, Germany) as-sembled with a 125 µm sieve was used to determine both residual fi nes (remaining un-agglomerated particles) and friability of the gran-ules [3].

CompressionThe single punch press XP 1 (Korsch GmbH, Berlin, Germany) as-sembled with a set of plane punches (diameter 8 mm) was used for compression.

Tensile strengthThe crushing force of the tablets was determined by using a multi-tester HT-TMB-CI-12 FS (Kraemer Elektronik GmbH, Darmstadt, Ger-many). Based on these results, tensile strength was calculated ac-cording to equation given in Figure 1.

Figure 1: �: tensile strength [N/mm²]; Fc: crushing force [N]; h: tablet height [mm]; d: diameter [mm]

� =2 · Fc

� · h · d

Results and DiscussionViscosity of the polymer solution plays a decisive role in a wet granu-lation process conducted in a fl uid bed granulator. The polymer solu-tion is administered via nozzles (in this case top spray) and its fl ow properties are strongly infl uencing both atomisation characteristics (such as droplet size and width of spray pattern) and maximum spray rate applicable.

The aqueous polymer solutions showed the typical dependency of dynamic viscosity on polymer content (Figure 2). As a consequence of the difference in molecular weight, PVP K90 resulted in much higher viscosity than PVP K25. The values of PVA-PEG were between those of both PVP grades.

Comparing the Wet Granulation Properties of PVA-PEG Graft Copolymer and different PVP Grades in Fluid Bed Granulation Processes applying different Spray RatesT. Agnese1, T. Cech1, V. Geiselhart2

1 European Pharma Application Lab, E-mail: thorsten.cech@basf.com, BASF SE, 67056 Ludwigshafen, Germany 2 Pharma Ingredients & Services Europe, BASF SE, 67056 Ludwigshafen, Germany

1.0E+00

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1.0E+03

1.0E+04

1.0E+05

0 5 10 15 20 25 30 35

Polymer concentration [%]

Log.

dyn

amic

vis

cosi

ty [m

Pas]

PVP K25 PVP K90 PVA-PEG copolymer

Figure 2: Dynamic viscosity of aqueous polymer solutions at 25 °Cas function of polymer concentration

The visual appearance of the fi nal granules was similar for the different binders (Figure 3 – Figure 5).

Figure 3: SEM picture of lactose agglomerates (produced at a spray rate of 21 g/min), using PVP K25 as binder

Figure 4: SEM picture of lactose agglomerates (produced at a spray rate of 21 g/min), using PVP K90 as binder

Figure 5: SEM picture of lactose agglomerates (produced at a spray rate of 21 g/min), using PVA-PEG copolymer as binder

The strength of the agglomerates is an important characteristic of the product. In comparison to high shear granulation, there is no solidi-fi cation taking place in fl uid bed processes. Therefore, viscosity re-lated aspects such as droplet size and drying speed are of utmost importance. The longer humidity is present on the particle’s surface, the higher the likelihood that during particle collision agglomeration takes place.Polymers such as PVP K90 offer a high molecular weight typically re-sulting in high viscosity and good binding properties of their solution. On the other hand, polymer solutions with low viscosity form weaker agglomerates holding a high amount of fi nes. The results of the ag-glomerates’ characterisation support this conclusion (Figure 6).Elevating spray rate while keeping inlet air temperature and volume constant is an appropriate measure to increase humidity during the agglomeration process. This is why agglomerates produced at higher

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