(208d) Application of Enhanced DEM Simulations for the Improvement of a Given Tablet Coating Process

An important
unit operation in the pharmaceutical industry is the coating of tablets. A
common technique is drum coating, where the tablets are placed in a rotating
drum and a coating liquid is sprayed onto the moving tablets. For most
applications, the uniformity of coating is of great importance. This includes
the even distribution of coating on single tablets, and the uniformity of
coating mass between the different tablets of a batch . The demand for process
understanding shows in the increasing number of investigations in recent years,
both experimentally[1] and using the Discrete Element Method (DEM)[2-4].

The aim of this
work is to improve the inter-tablet uniformity of a given coating process, and
to predict the scale-up behaviour. To this end, exhaustive investigations based
on DEM simulations are performed. Methods established in literature were
applied, and new models developed. For the simulations, the real geometry of
the apparatus was used. The material properties came from measurements, the operational
parameters were taken from a real coating process. To capture the spray itself,
two methods for the modelling of a spray in DEM simulations were implemented
(Fig. 1): : a user module for the DEM software that models the spray as
droplets (Fig. 1), and a ray-traced algorithm that operates on the output data
of a prior DEM simulation.

Figure 1:
DEM simulation of a tablet coating process, including the coating spray. The
spray droplets are colored in blue. The tablets are colored according to
coating mass, from light yellow (no coating mass) to red (high coating mass).

The basis for the
investigation is a full factorial 2³ Design of Experiments for the
lab-scale coater (BFC5, L.B. Bohle, Ennigerloh, Germany). The two spray models were
applied to extract detailed information on the spray process, such as coating
mass distribution or Single Visit Residence Time. First, a statistical analysis
of how the DoE parameters affect the product quality was done. Second, the
influence of the spray setup was studied in detail. This includes the geometry
of the spray zone, the number of nozzles, and the placement of them. Finally,
similar investigations were done for the pilot-scale to determine the scale-up
performance.

The results of
the DEM simulation give a deep understanding of a realistic coating process
from different angles. They point out the main influence factors, and show feasible
ways to improve the coating uniformity.

[1]           R.
Mueller and P. Kleinebudde, "Prediction of tablet velocity in pan coaters
for scale-up," Powder Technology, vol. 173, pp. 51-58, 2007.

[2]           M.
Kodam, J. Curtis, B. Hancock, and C. Wassgren, "Discrete element method
modeling of bi-convex pharmaceutical tablets: Contact detection algorithms and
validation," Chemical Engineering Science, vol. 69, pp. 587-601,
Feb 2012.

[3]           A.
Dubey, R. Hsia, K. Saranteas, D. Brone, T. Misra, and F. J. Muzzio,
"Effect of speed, loading and spray pattern on coating variability in a
pan coater," Chemical Engineering Science, vol. 66, pp. 5107 -
5115, 2011.

[4]           B.
Freireich, W. R. Ketterhagen, and C. Wassgren, "Intra-tablet coating
variability for several pharmaceutical tablet shapes," Chemical
Engineering Science, vol. 66, pp. 2535-2544, 2011.