Understanding tablet coating processes through DEMsimulation

[News vom: 11.11.2011]

Drum coating technology is widely used in the pharmaceutical industry to produce tablet films fulfilling functional and non-functional 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.

The uniformity of coating is of uttermost importance and represents critical issues in the production of this solid oral dosage forms. This includes both, inter-tablet uniformity [7] (variation of coating mass from one tablet to the other) and intra-tablet uniformity (variation of the coating thickness and quality on the surface of a single tablet) [5,6].

Although drum coating is a widespread technology in the pharmaceutical industry, numerical simulation of the process has been scarce so far, and process design is more often than not based on trial-and-error practices and operator experience. For this reasons, detailed investigation of the coating process and especially the uniformity of the coating using DEM simulations is of great interest for the pharmaceutical industry [1].

Beside experimental work [2,4], numerical simulations of particle motion using the Discrete Elements Method (DEM) have become an extremely important tool in particle technology problems and are frequently used for coater simulations [8]. 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. Based on a statistical Design of Experiment, important process attributes (e.g., residence time of the tablets under the coating spray, intra-tablet coating variability, tablets velocities pattern) are investigated for each point in the parameter space.

As a result, important process characteristics like mean particle velocity or rotational velocity were extracted and detailed investigation of e.g. local velocity variations were done. Another important quality attribute for tablet coating is the residence time distribution of the tablets in the spray zone. While this quantity is fastidious to extract by experimentation, it is readily available from the DEM simulations data. From this information, an expected coating variability and in the end coating process time can be estimated.

The DEM simulation has proven to be a valuable tool to gain understanding the dynamical behavior of the tablets under the spray gun. The gathered information is essential to 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.


  
Figure 1: Geometries of two tablet coating machines that were used in the simulations. Left: Driam Driaconti continuous coater, right: Bohle BFC5 lab-scale coater. The pictures were generated using the EDEM ® 2.3 particle simulation software.

 
Figure 2: Normalized time-averaged tablet velocity on the grid for round and bi-convex tablets at different coater rotation rates for a vertical slice in the middle of the coating apparatus.

References

  1. 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.

  2. Alexander, A., Shinbrot, T., Muzzio, F.J., 2002. Scaling surface velocities in rotating cylinders as a function of vessel radius, rotation rate, and particle size. Powder Technology 126, 174-190.

  3. Freireich, B., Wassgren, C., 2010. Intra-particle coating variability: Analysis and Monte-Carlo simulations, Chem. Eng. Sci. 65, 1117–1124.

  4. Ho, L., Müller, R., Römer, M., Gordon, K.C., Heinämäki, J., Kleinebudde, P., Pepper, M., Rades, T., Shen, Y.C., Strachan, C.J., Taday, P.F., Zeitler, J.A., 2007. Analysis of sustained-release tablet film coats using terahertz pulsed imaging. Journal of Controlled Release 119, 253-261.

  5. Kalbag, A., Wassgren, C., Penumetcha, S.S., Perez-Ramos, J.D., 2008. Inter-tablet coating variability: Residence times in a horizontal pan coater. Chem. Eng. Sci. 63, 2881-2894.

  6. Suzzi, D., Radl, S., Khinast, J.G., 2010. Local analysis of the tablet coating process: Impact of operation conditions on film quality. Chemical Engineering Science, Volume 65, Issue 21, Pages 5699-5715.

  7. 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.

  8. 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

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