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

Abstract

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 

Notes

Acknowledgment

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

References

  1. 1.
    S. M. Iveson, P. A. L. Wauters, S. Forrest, J. D. Lister, G. M. H. Meesters, and B. Scarlett. Growth regime map for liquid-bound granules: further development and experimental validation. Powder Technol. 117:83–97 (2001).CrossRefGoogle Scholar
  2. 2.
    T. Lipsanen, O. Anitikaninen, H. Räikkönen, S. Airaksinen, and J. Ylirruusi. Novel description of a design space for fluidized bed granulation. Int. J. Pharm. 345:101–107 (2007).PubMedCrossRefGoogle Scholar
  3. 3.
    B. Rambali, L. Baert, and D. L. Massart. Scaling up of the fluidized bed granulation process. Int. J. Pharm. 252:197–206 (2003).PubMedCrossRefGoogle Scholar
  4. 4.
    M. Levin (Ed.). Pharmaceutical process scale-up, 2nd edn., CRC, New York, 2006, pp. xii.Google Scholar
  5. 5.
    J. D. Cutnell, and W. J. Kenneth. Physics, 4th ed., Wiley, New York, 1998, p. 466.Google Scholar
  6. 6.
    M. Whitaker, G. R. Baker, J. Westrup, P. A. Goulding, D. R. Rudd, R. M. Belchamber, and P. C. Michael. Application of acoustic emission to the monitoring and end point determination of a high shear granulation process. Int. J. Pharm. 205:79–91 (2000).PubMedCrossRefGoogle Scholar
  7. 7.
    H. Tsujimoto, T. Yokoyama, C. C. Huang, and I. Sekiguchi. Monitoring particle fluidization in a fluidized bed granulator with an acoustic emission sensor. Powder Technol. 113:88–96 (2000).CrossRefGoogle Scholar
  8. 8.
    M. Halstensen, P. D. Bakker, and K. H. Esbensen. Acoustic chemometric monitoring of an industrial granulation production process—a PAT feasibility study. Chemome. Intell. Lab. Syst. 84:88–97 (2006).CrossRefGoogle Scholar
  9. 9.
    K. Naelapää, P. Veski, J. G. Pedersen, D. Anov, P. Jorgensen, H. G. Kristensen, and P. Bertelsen. Acoustic monitoring of a fluidized bed coating process. Int. J. Pharm. 332:90–97 (2007).PubMedCrossRefGoogle Scholar
  10. 10.
    S. Watano, and K. Miyanami. Image processing for on-line monitoring of granule size distribution and shape in fluidized bed granulation. Powder Technol. 83:55–60 (1995).CrossRefGoogle Scholar
  11. 11.
    Z. Q. Yu, R. B. H. Tan, and P. S. Chow. Effects of operating conditions on agglomeration and habit of paracetamol crystals in anti-solvent crystallization. J. Crystal Growth. 279:477–488 (2005).CrossRefGoogle Scholar
  12. 12.
    M. Li, D. Wilkinson, and K. Patchigolla. Obtaining particle size distribution from chord length measurements. Part. Part. Syst. Charact. 23:70–174 (2006).CrossRefGoogle Scholar
  13. 13.
    J. Worlitschek, and T. Hocker. Restoration of PSD from chord length distribution using the method of projects onto convex sets. Part. Part. Syst. Charact. 22:81–98 (2005).CrossRefGoogle Scholar
  14. 14.
    F. Sistare, L. S. P. Berry, and C. A. Mojica. Process Analytical Technology: an investment in process knowledge. Organic Process Res. Dev. 9:332–336 (2005).CrossRefGoogle Scholar
  15. 15.
    W. P. Findlay, R. P. Garnet, and K. R. Morris. Determination of fluidized bed granulation end point using near-infrared spectroscopy and phenomenological analysis. J. Pharm. Sci. 94:604–612 (2005).PubMedCrossRefGoogle Scholar
  16. 16.
    J. Rantanen, E. Rasanen, J. Tenhunen, M. Kansakoski, J.K. Mannermaa, and J. Yliruusi. In-line moisture measurement during granulation with a four-wavelength near infrared sensor: an evaluation of particle size and binder effects. Eur. J. Pharm. Biopharm. 50:271–276 (2000).PubMedCrossRefGoogle Scholar
  17. 17.
    J. Rantanen, S. Lehtola, P. Ramet, J. P. Mannermaa, and J. Yliruusi. On-line monitoring of moisture content in an instrumented fluidized bed granulator with a multi-channel NIR moisture sensor. Powder Technol. 99:163–170 (1998).CrossRefGoogle Scholar
  18. 18.
    P. Frake, D. Greenhalgh, S. M. Grierson, J. M. Hempenstall, and D. R. Rudd. Process control and end-point determination of a fluid bed granulation by application of near infra-red spectroscopy. Int. J. Pharm. 151:75–80 (1997).CrossRefGoogle Scholar
  19. 19.
    F. J. S. Nieuwmeyer, M. Damen, A. Gerich, F. Rusmini, K. V. D. V. Maarschalk, and H. Vromans. Granule characterization during fluid bed drying by development of a near infrared method to determine water content and median granule size. Pharm. Res. 24:1854–1861 (2007). doi: 10.1007/s11095-007-9305-5.PubMedCrossRefGoogle Scholar
  20. 20.
    B. J. Ennis, and J. D. Litster. Particle size enlargement. In R. Perry, and D. Green (eds.), Perry’s Chemical Engineers’ Handbook, 7th edn, McGraw-Hill, New York, 1997, pp. 20–56, 20–89.Google Scholar
  21. 21.
    K. P. Hapgood, S. M. Iveson, J. D. Lister, and L. X. Liu. Granulation rate processes. In A.D. Salman, M. J. Hounslow, and J. P. K. Seville (eds.), Handbook of powder technology, volume 11 Granulation, Elsevier, Oxford, 2007, pp. 899, 934–935.Google Scholar
  22. 22.
    D. Geldart. Types of fluidization. Powder Technol. 7:285 (1973).CrossRefGoogle Scholar
  23. 23.
    D. Kunii, and O. Levenspiel. Fluidization engineering, Butterworth-Heinemann, Toronto, 1991.Google Scholar
  24. 24.
    A. R. Heath, P. D. Fawell, P. A. Bahri, and J. D. Swift. Estimating average particle size by focused beam reflectance measurement (FBRM). Part. Part. Syst. Charact. 19:84–95 (2002).CrossRefGoogle Scholar
  25. 25.
    J. Worlitschek, and M. Mazzotti. Choice of the focal point position using Lasentec FBRM. Part. Part. Syst. Charact. 20:12–17 (2002).CrossRefGoogle Scholar
  26. 26.
    S. Watano. Direct control of wet granulation processes by image processing system. Powder Technol. 117:163–172 (2001).CrossRefGoogle Scholar
  27. 27.
    S. Wold, J. Cheney, N. Kettaneh, and C. McCready. The chemometric analysis of point and dynamic data in pharmaceutical and biotech production (PAT)—some objectives and approaches. Chemome. Intell. Lab. Syst. 84:159–163 (2006).CrossRefGoogle Scholar
  28. 28.
    G. Reich. Near-infrared spectroscopy and imaging: basic principles and pharmaceutical applications. Adv. Drug Deliver. Rev. 57:1109–1143 (2005).CrossRefGoogle Scholar

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

Personalised recommendations