Thursday, 07 March 2013 12:39

Experimental and Numerical Analysis of an Active Coating Process

Written by Sarah Just and Gregor Toschkoff
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DEM Simulation of tablet coating, using a custom spray model. The spray droplets are shown in cyan; tablets are colored according to coating mass. The image is taken after 2 revolutions of the drum. DEM Simulation of tablet coating, using a custom spray model. The spray droplets are shown in cyan; tablets are colored according to coating mass. The image is taken after 2 revolutions of the drum.


The inter-tablet coating uniformity is a critical quality attribute in active coating processes. In this project an active coating process is performed in order to produce a fixed dose combination of a sustained release formulation in the tablet core and an immediate release dose in the coating layer. The tablet cores consist of a push-pull osmotic system containing nifedipine as API (Adalat GITS). They are coated with Candesartan cilexetil as a second API. As the inter-tablet coating uniformity is a critical quality attribute to comply with regulatory requirements, the purpose of this work is to enhance the process understanding and to optimize the coating process with regard to the coating uniformity. Besides experimental investigations, PAT tools such as Raman spectroscopy [1] and terahertz pulsed imaging [2] have been applied to study this active coating process. In recent years, numerical simulations of coating processes have been gaining interest as analytical tool [3]. The discrete element method (DEM) in particular is suitable to simulate the tablet motion [4]. In this project, both experimental and numerical analysis of an active coating process is combined to investigate the influence of different process parameters with respect to the optimization of the coating uniformity.


DEM simulations

Using the DEM approach, the trajectories of individual particles (in this case tablets) can be computed. The basis of the calculation is Newton’s second law, which states that the acceleration of an object is given as the net force acting upon the object divided by the mass of the object: a = F / m. Knowing the forces of a particle of given mass, the current acceleration can be calculated. From this, the velocity and position of the particles after a small time interval (time-step) is ascertained by numerical integration. An analogous treatment gives the angle and angular velocity. The calculation is straightforward as long as tablets do not collide, however, this will inevitably occur. In the DEM approach the collisions of all particles with each other or the wall are tracked. If a collision is detected, the involved particles will overlap slightly; based on this a repulsive force (contact force) is calculated. To accurately calculate these mechanical contact forces, material and interaction properties of the tablets are required.


Application of the run-time spray modeling. The small blue spheres are the spray drops moving towards the tablet bed. When a drop hits a tablet, the coating mass gets increased, shown as an increasing red coloring of individual tablets. Load is 3.5 kg, rotation speed is 18 rpm. The process is shown at half speed.

Material properties

Measurements of important material properties which are needed as input for the DEM simulation were carried out. Young’s modulus, the coefficient of restitution as well as the coefficients of friction were determined experimentally. It was found that the direct measurement of the coefficients of friction is possible, but the obtained values were not representative for the process. Therefore, the dynamic angle of repose of a tablet bed in a rotating drum was investigated both experimentally and in DEM simulation [5]. By comparing the results from both, it was possible to determine the coefficients of friction as they appear in the rotating drum. For the experimental coating studies, a Bohle BFC 5 lab drum coater was used. 

Spray modelling

With the knowledge of the material properties from measurement and calibration, DEM simulations of the tablet motion in the drum were made. However, at this point such simulations only include tablets, and neglect the spray per se. Therefore, new methods to simulate spray processes had to be implemented. Different approaches were tested; it was shown that the best performance was given by a combination of two complementary methods [6]. First, a representation of the spray was included in the DEM simulations themselves. Second, the output data of prior simulation runs were investigated using a post-processing algorithm. The second depends on already existing data and therefore parameters such as drum rotation speed are fixed, but it is extremely fast if different spray settings (e.g., change the number of nozzles) are examined. DEM investigations were done for two scales of pan coaters (BFC 5 and BFC 50, Bohle).


DEM Simulation of tablets in a Bohle BFC 5 lab coater. A load of 3.5 kg tablets of standard round biconvex shape is filled in, approximated by a glued-sphere approach. They are colored to show the axial (front/back) mixing. Rotation speed is 18 rpm, the time span shown equals to 50 s process time, the video is therefore almost in real time.


With the measurements and developed methods, the active coating process can be investigated in detail. A statistical experimental plan was set up using the Design-of-Experiment (DoE) methodology. The DoE was then executed via experiment as well as DEM simulations. The main factors that were changed were rotation speed, pan load, and spray rate. After the process, the content uniformity of the API in the coating layer was assessed by calculating the coefficient of variation (CV) of the API between different tablets. Experimentally, this was done by performing HPLC analysis; in simulation, the spray modules explained above provide the required information on the coating mass on the single tablets.

By this, it was possible to investigate the influence of process parameters on the coating uniformity, and to study how the process can be optimized with respect to uniformity as well as process time. A decrease in spray rate and an increase in the rotation speed increased the coating uniformity which is consistent with results from previous studies. A complex interaction between pan load, tablet movement and the fraction of sprayed tablets was seen. The results lead to a not only qualitative, but quantitative assessment of the influences.



First comparisons of the experimental and simulation results show agreeing trends, however, this will be investigated in detail. To get an even deeper insight into the tablet movement, at the moment high-speed video imaging experiments are conducted; these will also pose an additional possibility for the validation of the DEM simulation. 


[1] M. Wirges, A. Funke, P. Serno, K. Knop, P. Kleinebudde, Monitoring of an active coating process for two-layer tablets-model development strategies, J. Pharm. Sci., (2012) doi:10.1002/jps.23383.

[2] D. Brock, J.A. Zeitler, A. Funke, K. Knop, P. Kleinebudde, A comparison of quality control methods for active coating processes, Int. J. Pharm., (2012), doi:10.1016/j.ijpharm.2012.09.021.

[3] G. Toschkoff, D. Suzzi, W. Tritthart, F. Reiter, M. Schlingmann, J.G. Khinast, Detailed analysis of air flow and spray loss in a pharmaceutical coating process, Aiche J., 58 (2012) 399-411 doi:10.1002/aic.12681.

[4] D. Suzzi, G. Toschkoff, S. Radl, D. Machold, S.D. Fraser, B.J. Glasser, J.G. Khinast, DEM simulation of continuous tablet coating: Effects of tablet shape and fill level on inter-tablet coating variability, Chem. Eng. Sci., 69 (2012) 107-121 doi:10.1016/j.ces.2011.10.009.

[5] S. Just, G. Toschkoff, A. Funke, D. Djuric, G. Scharrer, J. Khinast, K. Knop, P. Kleinebudde, Experimental Analysis of Tablet Properties for Discrete Element Modeling of an Active Coating Process, AAPS PharmSciTech, (2013) 1-10 doi:10.1208/s12249-013-9925-5.

[6] G. Toschkoff, S. Just, A. Funke, D. Djuric, K. Knop, P. Kleinebudde, G. Scharrer, and J. G. Khinast, "Spray Models for Discrete Element Simulations of Particle Coating Processes," submitted to Chem. Eng. Sci., 2013.

PSSRC Facilities

The research group of Professor Peter Kleinebudde in Düsseldorf is working on solid dosage forms and pharmaceutical processes like roll compaction / dry granulation, extrusion and coating. Recent topics of the focus group “Coating / Films” are pellet layering in different kinds of processing equipment, scale up of such processes, active coating on tablets, PAT with Raman spectroscopy and terahertz pulsed imaging, simulation and experimental verification of coating processes in drum coaters and solvent film casting of orodispersible dosage forms.

The simulation work presented here is done in the group “Modeling and Prediction” working under Professor Johannes Khinast at the Technical University of Graz, which has comprehensive experience in the investigation of tablet coating using DEM.

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