Implementation of real-time and in-line feedback control for a fluid bed granulation process

Theresa Reimers, Jochen Thies, P. Stöckel, Stefan Dietrich, Miriam Pein-Hackelbusch, Julian Quodbach*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


The application of process analytical technologies (PAT) to monitor critical quality attributes (CQAs) provides an important approach to enhance process understanding and improve the reliability of pharmaceutical production processes. The present study focuses on the first PAT based feedback control system for a fluid bed granulation batch process. Real-time particle size measurement by in-line spatial filtering technique (SFT) using a modified time-based buffer system was applied to define a target particle size after spraying a specific amount of binder solution. After identifying an appropriate control variable, a suitable strategy for feedback control was established, followed by tuning of the control loop to obtain best performance of the integrated system. By adapting the final target particle size within a specified range good functionality of the system could be demonstrated. Investigations of the robustness further showed that the implemented system enables the production of a predefined target particle size also by varying process and formulation parameters. The effect of increasing spray rates and binder concentrations on the particle size could be compensated in a given range by feedback control ensuring a predefined product quality. The study provides an advanced approach for quality assurance of fluid bed granulation.

Original languageEnglish
Article number118452
JournalInternational Journal of Pharmaceutics
Publication statusPublished - 15 Aug 2019


  • Fluid bed granulation
  • In-line particle size measurement
  • Process analytical technologies
  • Process automation
  • Spatial filtering technology


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