(13f) Experimental Investigation and Modelling of the Deformation Behavior of Pharmaceutical Pellets As a Basis for DEM Simulations of the Spheronization Process

Weis, D. - Presenter, Technische Universität Kaiserslautern
Niesing, M., TU Dortmund
Thommes, M., TU Dortmund University
Antonyuk, S., Technische Universität Kaiserslautern

Spherical granules with a narrow size
distribution and a regular shape are highly interesting for pharmaceutical
applications. To produce such pellets, a combined extrusion and spheronization
process is widely used. A spheronizer consists of a stationary cylindrical wall
and a rotating disk with a structured surface. The rounding of the cylindrical
extrudates is influenced by various overlapping mechanisms. An important factor
affecting those mechanisms is the particle dynamics in the spheronizer, which
depends on the process conditions and the pellets properties. The simulation of
the particle dynamics with the Discrete Element Method (DEM) is a useful tool
to get detailed information of what happens during the pellet rounding. In
addition to particle kinematics and collision characteristics, other effects
like segregation and mixing can be analyzed.

For the prediction of real particle
interactions, the contact behavior of the simulated pharmaceutical pellets needs
to be modelled with a suitable model. For this purpose, the deformation
behavior was estimated experimentally in single particle uniaxial compression
tests with the Texture Analyser (TA.XTplus, Stable Micro Systems, UK). The obtained
force-displacement curves were used to develop a contact model which describes
the particle interactions in the simulation. In the quasistatic compression
tests, viscous effects cannot be investigated. Therefore additionally impact
tests at different impact velocities were performed in addition to the
compression tests as shown in [1] and considered in the model.

For the experiments pellets were produced
with the combined extrusion and spheronization process. A mixture consisting of
microcrystalline cellulose (Vivapur 102, JRS Pharma, Germany) with a mass
fraction wi = 0.2 g/g and α-lactose monohydrate (Granulac 200,
Meggle, Germany) with wi = 0.8 g/g was extruded (Micro 27 GL-28D,
Leistritz, Germany) with water at 300 rpm. Afterwards, 450 g of the extrudates
were spheronized in a lab scale spheronizer (RM300, Schlüter, Germany) with a
rotational speed of the friction plate of 750 rpm for 5 minutes.

The spheronized pellets have a high
moisture content of about 40%. Since the moisture has a significant impact on
the deformation and breakage behavior, drying of the pellets during the compression
tests must be avoided. For that reason, the compression tests were performed in
a climatic chamber, where the temperature and the moisture can be controlled. During
the spheronization process, the pellets undergo multiple loadings. To study the
cyclic deformation behavior cyclic compression tests of pellets at different
force levels and stress rates were carried out.

In our previous works [2, 3], the
force-displacement curve were approximated with linear relations according to
the model of Walton&Braun [4, 5]. In [6] different approaches to model
plastic material behavior based on the work of Tomas and Luding can be found. In
this contribution, a new contact model is presented. The force-displacement
relationship during loading and reloading is still modelled using a linear function,
however the unloading stage is approximated with a power law to further
increase the accordance of model and experiment. Moreover, the change in
stiffness for reloading because of plastic deformation and consolidation in the
contact area is considered, using the flattening of the particle. The force
displacement curves of the linear and the new model are shown in figure 1 with a
characteristic experimental result.

1: Force displacement curves of the linear and the new model compared with a
characteristic experimental result

DEM simulations of the particle dynamics in
a spheronization process were performed using the developed contact model and
compared against simulations based on the linear contact model regarding
computing time and deviation of the results. The collision rates and forces of
the pellet interaction with other pellets and the apparatus walls were in
particular focus. Distributions of the collision rates and the time averaged
collision forces in the spheronizer were obtained.


[1]          Antonyuk, S., Heinrich, S., Tomas, J., Deen, N.G., van
Buijtenen, M.S. and J.A.M. Kuipers: Energy absorption during compression and
impact of dry elastic-plastic spherical granules, Granular Matter 1(12), 2010,

[2]          Weis, D., Antonyuk, S.; Thäte, D.; Thommes, M.: DEM
Simulations of Particle Dynamics in a Spheronization Process to describe the
Pelletization Mechanisms. IV International Conference on Particle-Based
Methods, Proceedings, ISBN 978-84-944244-7-2, S. 567-578

[3]          Weis, D., Antonyuk, S., Thommes M.: Manufacturing of
Pharmaceutical Pellets by Spheronization - DEM Simulation of Particle
Kinematics. PARTEC 2016, International Congress for Particle Technology,

[4]          Walton, I. OR, and R. L. Braun: Stress calculations for
assemblies of inelastic speres in uniform shear. Acta mechanica 63(1-4), 1986,

[5]          Walton, O. R., Braun, R. L.: Viscosity,
granular‐temperature, and stress calculations for shearing assemblies of
inelastic, frictional disks. Journal of Rheology 30(5), 1986, 949-980.

[6]          Tykhoniuka, R. et al.: Ultrafine cohesive
powders: From interparticle contacts to continuum behavior. Chemical
Engineering Science 62, 2007, 2843 – 2864.