Optimization and Scale-Up of a Coating Process

Abstract
In the pharmaceutical industry, drum coating is a common unit operation for the production of tablet films. The applied coating layer(s) may have various functions, such as taste masking and colouring, active pharmaceutical ingredient (API) release modification or applying of an additional API. The uniformity of the coating is crucial. In recent years, parallel to an increased experimental effort, numerical simulations of particle motion using the Discrete Elements Method (DEM) have proven to be an important tool for studying the tablet coating process. This project combines lab- and pilot-scale experiments with DEM simulations to investigate the influence of different process parameters and to optimize the coating uniformity.

Project goals

• Understanding the influence of process parameters on the morphology and inter- and intra-tablet uniformity of the coating layer.
• Development of a modeling tool for the prediction of the coating process performance with regard to coating uniformity and coating quality.
• Investigations of the scale-up performance of the process (moving from the lab- to pilot- to the industrial scale)
• Application of experiments and computational simulations to investigate and optimize the product quality
• Definition of critical quality attributes (CQAs), i.e., those that must be ensured regardless of the system and operational parameters, description of the interconnections of product quality using a Quality-by-Design approach and application of Process Analytical Technology (PAT) to the monitoring and control of the process.
• Development of a reliable and scalable process for the production of tablets with a well-defined coating mass distribution.

Present Project Results
During the current first phase of the project, measurements of important material properties that are crucial for the process and are needed as input for the DEM simulation (e.g., friction coefficients, coefficient of restitution, Young’s modulus) have been performed. For the experimental coating studies, a Bohle BFC5 lab coater has been set up. Various measurement techniques have been applied and evaluated. As for the simulation part, DEM investigations of Bohle BFC5/50 apparatus have been performed. The first simulation results have provided insights into the tablets’ behaviour in a coating drum. Based on this, novel methods for the description of sprays for DEM simulations have been developed.

Project Challenges
Optimization of the coating process and, especially, minimization of the coating uniformity require a detailed understanding of how the process parameters affect the output quality. The challenges are the novel combination of experimental and computational investigations and the development of methods for obtaining new information regarding coating uniformity from both experiments and simulations.