Production of Tablets at RCPE’s Continuous Wet Granulation Tableting Line
T.R. Hörmann, M. Kreimer, V. Demiri, J. Rehrl, J.A. Afonso Urich, R.G. Lara Garcia, W.-K. Hsiao, J.G. Khinast
With the shift towards continuous manufacturing in the pharmaceutical production of oral solid dosage forms (ODFs), especially direct compression (DC) and continuous wet granulation (WG) have major interest in research and industry. Wet granulation is typically applied, when direct compression is not feasible due to poor compressibility or segregation issues in the given formulation.
As one of the first equipment providers, GEA has developed a turn-key continuous wet granulation and tableting line, i.e., the ConsiGmaTM 25 continuous tableting line (CTL). The line is composed of the following, fully interlinked units: i) a continuous feeding and twin-screw wet granulation (TSWG), ii) a six-segmented continuously-operated fluid bed dryer (FBD), iii) a granule conditioning unit (GCU) with a conical mill, a scale and a mini-batch ribbon blender, and finally, iv) a tablet press. The continuous operation of the whole process line is achieved by the connection of sub-units via pneumatic transfer lines. Thus, the process conditions for intermediate products and blends are significantly different from batch manufacturing.
In our use-case study, a finely milled and an unmilled tracer material was added to the granules as an external excipient in the line’s mini-batch ribbon blender. After adding the lubricant, the produced compression mix was transferred to the tablet press and compressed to tablets. The final tablet’s tracer content was evaluated and compared for both tracers to assess the effect of particle size on content uniformity. Surprisingly, tablets were less uniform for the milled tracer material, contradicting findings from offline sifting segregation tests. A thorough root-cause analysis for these observations will be presented, considering the process conditions in feeding, blending, the pneumatic transfer line and in the tablet press. Based on different segregation mechanism models, hypotheses are developed and challenges and benefits in continuous pharmaceutical manufacturing lines demonstrated.
Theresa obtained her doctoral degree in chemical engineering at the Institute of Process and Particle Engineering of the Graz University of Technology, Austria, in 2019.
During her doctoral studies she worked on the development of a continuous process line to produce tablets via hot-melt extrusion and pelletisation, following the principles of Quality by Design. Her PhD project was one of three use case streams in the European Consortium on Continuous Pharmaceutical Manufacturing (ECCPM). In addition, Theresa taught courses on particle technology and pharmaceutical engineering at TU Graz.
After completing her doctoral studies, she joined the Research Center Pharmaceutical Engineering (RCPE), where she is working as a Senior Scientist. As an expert in continuous processing, she is scientifically leading a project to develop a “Material Science Knowledge Base” as well as RCPE’s team for continuous granulation using a GEA ConsiGma® 25 continuous manufacturing line. Her ongoing research focus is in process development, in combination with material science for powders.