(666b) Investigation of Tablet Coating Processes Using Discrete Element Method Simulations

Investigation
of tablet coating processes using Discrete Element Method simulations

G. Toschkoff¹, D. Suzzi¹,
S. Just², K. Knop², P. Kleinebudde², J. G.
Khinast^1,3

¹ Research
Center Pharmaceutical Engineering GmbH, Graz, Austria

² Institute
of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Düsseldorf,
Germany

³ Institute
for Process and Particle Engineering, Graz University of Technology, Graz,
Austria

In
the pharmaceutical industry, drum coating is a widely used unit operation to
produce tablet films of different purposes. In this process, a rotating drum
accounts for the necessary mixing of the tablets, and a coating solution is
injected from above by means of an atomizing nozzle. The applied
coating layer(s) fulfill different functions, e.g. taste masking and coloring,
control of the release of the active pharmaceutical ingredient (API) from the
core of a tablet, application of an additional API, or protection of the tablet
core from environmental influences.

For
all aspects of the coating mentioned above, the uniformity of coating is of great
importance. This includes both, inter-tablet uniformity and intra-tablet
uniformity. In fact, as inhomogeneity in the coating thickness can lead to serious
hazards (e.g., significant variations in APIs delivery rate), a single tablet
that fails testing can lead to the rejection of the whole batch.

Although
drum coating is a widespread technology in the pharmaceutical industry, process
design is more often than not based on trial-and-error practices and operator
experience. In recent years, parallel to an increased effort in experimental
work [1], numerical simulations of particle motion using the Discrete Elements
Method (DEM) have proven to be an important tool in the detailed investigation
of the tablet coating process, as well as in other particle-based
pharmaceutical processes [2,3].

Figure 1: Examples
of DEM simulations in two tablet coating apparatus that were used in this work.
Left: Driam Driaconti cycled continuous coater, right: Bohle BFC5 lab-scale
coater.

The aim of this work is to
analyze and understand the effects of parameters like tablet form, fill volume or
pan rotation speed on the intra-tablet coating variability [3] in different
coating devices. To this end, DEM simulations are performed to numerically
reproduce the tablet motion inside different coating machines. Material
parameters needed for the simulation are gathered from measurements. For each
geometry, different tablet shapes, namely bi-convex, oval and/or round, are
modeled by the ?glued spheres? approach. Further parameter variations include
different fill volumes or different rotational speeds.

Important process attributes
that one wants to know are, e.g., residence time of the tablets under the
coating spray, intra-tablet coating variability, or tablets velocities pattern.
While many of these quantities are fastidious or even impossible to get by
experimentation, they are readily extracted from the DEM simulations results.

In the following, two
examples of the acquired information are given. Figure 2 shows a matrix of the
mean velocity of the tablets, for different fill levels and different tablet
shapes, allowing a direct qualitative and quantitative comparison of the
different setups.

Figure 2: Normalized
time-averaged tablet velocity on the grid for round, oval and bi-convex tablets
at the different coater fill ratios for a vertical slice in the middle of the
coating apparatus. From [4]

Figure 3 shows the fractional residence time,
i.e., the ratio between the time spent by a tablet in the spray zone located at
the top of the surface and the total coating time, for the Driam continuous
coater for a simulation time of 60 seconds. It can be seen that both tablet
shape (quantified as length-to-height ratio) and fill level have an influence
on the time that a single tablet spends exposed to the spray. From this
information, an expected coating variability and in the end coating process
time can be estimated.

Figure 3 Average
fractional RT in the spray zone for round, oval and bi-convex tablets at the
coater fill ratios.

Conclusion

The DEM
simulation has proven to be a valuable tool to gain understanding the dynamical
behavior of the tablets. The gathered information is essential to e.g. obtain a
satisfactory intra-tablet coating homogeneity, which in turn is necessary to minimize
the number of tablet batches that have to be rejected. The outcomes of this
work aims at demonstrating the utility of numerical simulation in the
development and the design of pharmaceutical tablet coating processes.

References

1.        
Tobiska,
S., Kleinebudde, P., 2003. Coating uniformity and coating efficiency
in a Bohle Lab-Coater using oval tablets. European Journal of Pharmaceutics
and Biopharmaceutics 56, 3-9.

2.        
Adam,
S., Suzzi, D., Radeke, C., Khinast, J.G., 2010. An integrated Quality
by Design (QbD) approach towards design space definition of a blending unit
operation by Discrete Element Method (DEM) simulation. European Journal of
Pharmaceutical Sciences, In Press.

3.          
Ketterhagen,
W. R.; am Ende, M. T. & Hancock, B. C., 2009, Process modeling in
the pharmaceutical industry using the discrete element method, Journal of
Pharmaceutical Sciences, , 98, 442-470

4.          
Suzzi,
D.; Toschkoff, G; Radl, S.; Machold, D.; Fraser, S. D.; Glasser B. J.; Khinast,
J. G, 2011, DEM Simulation of Continuous Tablet Coating: Effects of
Tablet Shape and Fill Level on Inter-Tablet Coating Variability. Submitted
to Chemical Engineering Science.