Comparing the Wet Granulation Properties of PVA-PEG

Graft Copolymer and different PVP Grades in High Shear

Granulation Processes using various Binder Concentrations
T. 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

Purpose 1.0E+05
60
PVA-PEG graft copolymer is originally intended for instant release film
coating applications. However, the polymer offers excellent wet bind-

Log. dynamic viscosity [mPas]

1.0E+04 50
ing properties as well. Since this synthetic polymer is peroxide-free, it

Fine / friability [%]

can be considered as binder for actives being vulnerable to oxidation 40
[1]. 1.0E+03

To evaluate the wet granulation properties of PVA-PEG, the findings 30

were compared to those of polyvinylpyrrolidone (PVP) which can be 1.0E+02 20

considered as standard binding agent. Different grades are available,
varying in molecular weight, viscosity and K-value respectively. Typi- 10
1.0E+01
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 0
K90 differs distinctively in regard to binding capabilities and viscosity 1.0E+00 1.5 3.0 5.0 1.5 3.0 5.0 1.5 3.0 5.0
of its aqueous solutions [2]. 0 5 10 15 20 25 30 35 PVP K25 PVP K90 PVA-PEG
The aim of this work was to compare the wet binding properties of Polymer concentration [%]
Binder / binder content [%]
PVA-PEG graft copolymer and the PVP grades K25 and K90 in a high PVP K25 PVP K90 PVA-PEG copolymer Fine Friability
shear granulation process.
Figure 2: Dynamic viscosity of aqueous polymer solutions at 25 °C Figure 6: Fines and friability after 15 minutes testing time as function
as function of polymer concentration of polymer content and type of binder
Materials and Methods
Materials
As wet binders, the PVP grades K25 (Kollidon® 25), K90 (Kollidon® The visual appearance of the final granules was similar for the different 1.0

90F) and PVA-PEG graft copolymer (Kollicoat® IR) were tested. All binders (Figure 3 – Figure 5).

Particle size distribution [-]

three products are supplied by BASF SE, Ludwigshafen, Germany. As 0.8

filling material, a special lactose grade for wet granulation (GranuLac®

200, Molkerei Meggle GmbH & Co. KG, Wasserburg, Germany) was 0.6
used.
Methods 0.4

The granulation process was performed according to the schema

shown in Table 1. 0.2

Table 1: Schema of the trial set-up in high shear granulator

0.0
1.5 3.0 5.0 1.5 3.0 5.0 1.5 3.0 5.0
Batch size 400 g
PVP K25 PVP K90 PVA-PEG
Impeller speed 200 rpm
Polymer / polymer content [%]
Chopper speed 2,200 rpm
Process time 15 min <125µm 125-355µm >355µm

Screening 1.6 mm (wet) Figure 7: Classified particle size distribution as function of polymer
0.8 mm (dry) content and type of binder
Drying time (fluid bed) 30 min
Figure 3: SEM picture of lactose agglomerates, using PVP K25 as The amount of binder influenced the hardness of the agglomerates as
In all trials, the binders were applied as aqueous solutions, whereas binder well as the tensile strength of the tablets. In this investigation, it could
the amount of polymer dissolved in 50 g of water was chosen to lead be shown that higher binder contents led to harder tablets, whereas
to a final binder content of 1.5, 3.0 or 5.0 % in the resulting granules. this effect was more pronounced for PVA-PEG (Figure 8).
Of all granules, particle size distribution and friability were determined.
All granules were compressed into tablets applying a compression
8
force of 15 kN.
Viscosity
In order to test the rheological investigations on dynamic viscosity, the
Tensile strength [N/mm²]

6
Thermo Scientific HAAKE RotoVisco 1 rotational rheometer (Thermo
Fisher Scientific, Karlsruhe, Germany) with liquid temperature control
for concentric cylinder measuring geometries was used.
4
Granulation
As high shear granulator, the P1-6 (Diosna GmbH, Osnabrück, Ger-
many) assembled with 2 L product bowl was used (Table 1). 2
Particle size distribution
The test was performed with a sieve tower Retsch AS 200 (Retsch
GmbH, Haan, Germany) by using sieves in the range of 38–500 µm 0
(according to Ph. Eur.). The results were categorised into three differ- 1.5 3.0 5.0 1.5 3.0 5.0 1.5 3.0 5.0
ent particle size classes: coarse (> 355 µm), mean (125–355 µm) and Figure 4: SEM picture of lactose agglomerates, using PVP K90 as PVP K25 PVP K90 PVA-PEG
fine (< 125 µm) particles. binder
Friability Figure 8: Tensile strength of tablets
An air jet sieve LPS 200 (Rhewum GmbH, Remscheid, Germany) as-
sembled with a 125 µm sieve was used to determine both residual
fines (remaining un-agglomerated particles) and friability of the gran-
ules [3]. Conclusion
Compression PVP K90 was found to be the strongest binder in the test, es-
The single punch press XP 1 (Korsch GmbH, Berlin, Germany) pecially when used in high concentrations such as 5 %. Yet,
equipped with a set of flat punches (diameter 8 mm) was used for depending on the application, the high viscosity of the poly-
compression. mer solutions could limit its use.
PVA-PEG graft copolymer was found to be an interesting al-
Tensile strength ternative, because it offered a moderate viscosity. The result-
The crushing force of the tablets (n = 20) was determined by using a ing granulation process was very robust leading to constant
multi-tester HT-TMB-CI-12 FS (Kraemer Elektronik GmbH, Darmstadt, particle size distributions and strong agglomerates inde-
Germany). Based on these results, tensile strength was calculated ac- pendent of the amount of binder used. These granules result-
cording to equation given in Figure 1. ed in tablets yielding very high hardness.
The peroxide free PVA-PEG copolymer is an efficient binder
2 · Fc combining low viscosity of the polymer solution and strength
= Figure 5: SEM picture of lactose agglomerates, using PVA-PEG as
of the final agglomerates which in turn led to high tablets
hardness.
·h·d binder

Figure 1: : tensile strength [N/mm²]; Fc: crushing force [N]; References

h: tablet height [mm]; d: diameter [mm]
Results and Discussion
Viscosity of the polymer solution plays a decisive role in high shear
wet granulation processes, since it is responsible for the time needed
to incorporate the binder into the powder components. Additionally,
the way of administering a binder solution is also determined by vis-
cosity.
The dynamic viscosity of the aqueous polymer solutions showed the
typical dependency on polymer content (Figure 2). As a consequence
of a 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.
Strength of the particles is one of the most important parameters,
in regard to the quality of an agglomerated product. Friability data
indicate that the strength did clearly depend on the binder content. In
general, the lowest friability values could be found for those granules
holding binder contents of 5 % (Figure 6). For lower binder contents
such as 1.5 and 3.0 %, PVA-PEG gave the best results. The effect of
binder content on fines is markedly low (blue bars). Almost every trial
resulted in un-agglomerated particles with a quantity of 10 to 15 %.
The same result in regard to fines could be seen in the particle size
distribution, where almost the same amount of un-agglomerated par-
ticles could be found for all granules tested (Figure 7). Interestingly, for
PVA-PEG the fraction of mean and coarse particles was quite inde-
pendent from the amount of applied binder. This leads to the assump-
tion that the process should be quite robust.
[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.
2nd Conference Innovation in Drug Delivery; October 3–6, 2010;
Aix-en-Provence, France; G-EMP/MD302

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