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.