AAPS PharmSciTech

, Volume 9, Issue 4, pp 1083–1091 | Cite as

Monitoring Granulation Rate Processes Using Three PAT Tools in a Pilot-Scale Fluidized Bed

  • Ai Tee Tok
  • Xueping Goh
  • Wai Kiong Ng
  • Reginald B. H. Tan
Research Article


The purpose of this research was to analyze and compare the responses of three Process Analytical Technology (PAT) techniques applied simultaneously to monitor a pilot-scale fluidized bed granulation process. Real-time measurements using focused beam reflectance measurement (Lasentec FBRM) and near-infra red spectroscopy (Bruker NIR) were taken by inserting in-line probes into the fluidized bed. Non-intrusive acoustic emission measurements (Physical Acoustic AE) were performed by attaching piezoelectric sensors on the external wall of the fluidized bed. Powder samples were collected at regular intervals during the granulation process and characterized offline using laser diffraction, scanning electron microscopy, stereo-optical microscopy and loss on drying method. PAT data comprising chord length distribution and chord count (from FBRM), absorption spectra (from NIR) and average signal levels and counts (from AE) were compared with the particle properties measured using offline samples. All three PAT techniques were able to detect the three granulation regimes or rate processes (wetting and nucleation, consolidation and growth, breakage) to varying degrees of sensitivity. Being dependent on optical signals, the sensitivities of the FBRM and NIR techniques were susceptible to fouling on probe windows. The AE technique was sensitive to background fluidizing air flows and external interferences. The sensitivity, strengths and weaknesses of the PAT techniques examined may facilitate the selection of suitable PAT tools for process development and scale-up studies.

Key words

acoustic emission FBRM granulation near-infra red PAT 



This work was supported by the Science and Engineering Research Council of A*STAR (Agency for Science, Technology and Research).


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Copyright information

© American Association of Pharmaceutical Scientists 2008

Authors and Affiliations

  • Ai Tee Tok
    • 1
  • Xueping Goh
    • 1
  • Wai Kiong Ng
    • 1
  • Reginald B. H. Tan
    • 1
    • 2
  1. 1.Crystallisation and Particle Sciences, Institute of Chemical and Engineering SciencesAgency for Science Technology and Research (A*STAR)SingaporeSingapore
  2. 2.Department of Chemical and Biomolecular EngineeringThe National University of SingaporeSingaporeSingapore

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