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Process analysis of fluidized bed granulation

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Abstract

This study assesses the fluidized bed granulation process for the optimization of a model formulation using in-line near-infrared (NIR) spectroscopy for moisture determination. The granulation process was analyzed using an automated granulator and optimization of the verapamil hydrochloride formulation was performed using a mixture design. The NIR setup with a fixed wavelength detector was applied for moisture measurement. Information from other process measurements, temperature difference between process inlet air and granules (Tdiff), and water content of process air (AH), was also analyzed. The application of in-line NIR provided information related to the amount of water throughout the whole granulation process. This information combined with trend charts of Tdiff and AH enabled the analysis of the different process phases. By this means, we can obtain in-line documentation from all the steps of the processing. The choice of the excipient affected the nature of the solid-water interactions; this resulted in varying process times. NIR moisture measurement combined with temperature and humidity measurements provides a tool for the control of water during fluid bed granulation.

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References

  1. Callis J, Illman D, Kowalski B. Process analytical chemistry. Anal Chem. 1987;59:624A-637A.

    Article  CAS  Google Scholar 

  2. Beebe K, Blaser W, Bredeweg R, et al. Process analytical chemistry. Anal Chem. 1993;65:199R-216R.

    Article  CAS  Google Scholar 

  3. Zografi G. States of water associated with solids. Drug Dev Ind Pharm. 1988;14:1905–1926.

    Article  CAS  Google Scholar 

  4. Brittain H. Methods for the characterization of polymorphs and solvates. In: Brittain H, ed. Polymorphism in pharmaceutical solids. 1st ed. New York: Marcel Dekker Inc; 1999:227–278.

    Google Scholar 

  5. Schaefer T, Wørts O. Control of fluidized bed granulation III. Effect of inlet air temperature and liquid flow rate on granule size and size distribution. Control of moisture content of granules in the drying phase. Arch Pharm Chem Sci. 1978;6:1–13.

    CAS  Google Scholar 

  6. Abberger T, Raneburger J, Egermann H. Instrumentation of laboratory-scale fluid-bed granulator for critical moisture content and of free moisture. Sci Pharm. 1996;64:255–262.

    CAS  Google Scholar 

  7. Wöstheinrich K, Schmidt P. Evaluation and validation of a fully instrumented Hüttlin HKC 05-TJ laboratory-scale fluidized bed granulator.Drug Dev Ind Pharm.2000;26:621–633.

    Article  PubMed  Google Scholar 

  8. Workman J, A review of process near infrared spectroscopy: 1980–1994. J Near Infrared Spectrosc. 1993;1:221–245.

    Article  CAS  Google Scholar 

  9. Axon T, Brown R, Hammond S, Maris S, Ting F. Focusing near infrared spectroscopy on the business objectives of modern pharmaceutical production. J Near Infrared Spectrosc. 1998;6:A13-A19.

    Article  CAS  Google Scholar 

  10. Kamat MS, Lodder RA, DeLuca PP. Near-infrared spectroscopic determination of residual moisture in lyophilized sucrose through intact glass vials.Pharm Res.1989;6:961–965.

    Article  CAS  PubMed  Google Scholar 

  11. Osborne BG, Fearn T, Hindle PH. In: Practical NIR Spectroscopy with Applications in Food and Beverage Industry Analysis. 2nd ed. Harlow, UK: Longman; 1993:227.

    Google Scholar 

  12. Watano S, Terashita K, Miyanami K. Development and application of infrared moisture sensor to complex granulation. Bull Univ Osaka Pref, Series A. 1990;39(2):187–197.

    CAS  Google Scholar 

  13. White J. On-line moisture detection for a microwave vacuum dryer.Pharm Res.1994;11:728–732.

    Article  CAS  PubMed  Google Scholar 

  14. Frake P, Greenhalgh D, Grierson S, Hempenstall J, Rudd D. Process control and end-point determination of a fluid bed granulation by application of near infra-red spectroscopy. Int J Pharm. 1997;151:75–80.

    Article  CAS  Google Scholar 

  15. Goebel S, Steffens K. Online-messung der Produktfeuchte und Korngröße in der Wirbelschnicht mit der Nah-Infrarot-Spektroskopie. Pharm Ind. 1998;60:889–895.

    CAS  Google Scholar 

  16. Rantanen J, Lehtola S, Rämet P, Mannermaa J-P, Yliruusi J. On-line monitoring of moisture content in an instrumented fluidized bed granulator with a multichannel NIR moisture sensor. Powder Technol. 1998;99:163–170.

    Article  CAS  Google Scholar 

  17. Luukkonen P, Rantanen J, Mäkelä K, Räsänen E, Tenhunen J, Yliruusi J. Characterization of silicified microcrystalline cellulose and a-lactose monohydrate wet masses using near infrared spectroscopy.Pharm Dev Technol.2001;6:1–9.

    Article  CAS  PubMed  Google Scholar 

  18. Räsänen E, Rantanen J, Jørgensen A, Karjalainen M, Paakkari T, Yliruusi J. Novel identification of pseudopolymorphic changes of theophylline during wet granulation using near infrared spectroscopy.J Pharm Sci.2001;90:389–396.

    Article  PubMed  Google Scholar 

  19. Iwamoto M, Uozumi J, Nishinari K. Preliminary investigation of the state of water in foods by near infrared spectroscopy. Budapest, Hungary. Intl NIR/NIT Conference; 1987:3–12.

  20. Delwiche S, Pitt R, Norris K. Examination of starch-water and cellulose-water interactions with near infrared (NIR) diffuse reflectance spectroscopy. Starch/Stärke. 1991;43:415–422.

    Article  CAS  Google Scholar 

  21. Rantanen J, Känsäkoski M, Suhonen J, et al. Next generation fluidized bed granulator automation. AAPS PharmSciTech 2000;1(2) Available from:http://www.aapspharmaceutica.com/scientificjournals/ pharmscitech/volume1issue2/014/manuscript.htm

  22. Rantanen J, Räsänen E, Mannermaa J-P, Yliruusi J. 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.2000;50:271–276.

    Article  CAS  PubMed  Google Scholar 

  23. Rantanen J, Laine S, Antikainen O, Mannermaa J-P, Simula O, Yliruusi, J. Visualization of pharmaceutical unit operations using self-organizing maps (SOM).J Pharm Biomed Anal.2001;24:343–352.

    Article  CAS  PubMed  Google Scholar 

  24. Morris K, Stowell J, Byrn S, Placette A, Davis T, Peck G. Accelerated fluid bed drying using NIR monitoring and phenomenological modeling.Drug Dev Ind Pharm.2000;26:985–988.

    Article  CAS  PubMed  Google Scholar 

  25. Watano S. Mechanism and control of granule growth in fluidized bed granulation [dissertation]. Osaka, Japan: College of Engineering, University of Osaka; 1995.

    Google Scholar 

  26. Watano S, Takashima H, Sato Y, Miyanami K, Yasutomo T. IR absorption characteristics of an IR moisture sensor and mechanism of water transfer in fluidized bed granulation. Adv Powder Technol. 1996;7:279–289.

    Article  CAS  Google Scholar 

  27. Miwa A, Yajima T, Itai S. Prediction of suitable amount of water addition for wet granulation.Int J Pharm.2000;195:81–92.

    Article  CAS  PubMed  Google Scholar 

  28. Schmidt C, Kleinebudde P. Influence of the granulation step on pellets prepared by extrusion/spheronization. Chem Pharm Bull. 1999;47:405–412.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Viikki Drug Discovery Technology Center, Pharmaceutical Technology Division, University of Helsinki, PO Box 56, FIN-00014, Finland

    Jukka Rantanen & Jouko Yliruusi

  2. Pharmaceutical Technology Division, University of Helsinki, PO Box 56, FIN-00014, Finland

    Jukka Rantanen, Anna Jørgensen, Eetu Räsänen, Pirjo Luukkonen, Sari Airaksinen, Johanna Raiman, Kaisa Hänninen, Osmo Antikainen & Jouko Yliruusi

Authors
  1. Jukka Rantanen
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  2. Anna Jørgensen
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  3. Eetu Räsänen
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  4. Pirjo Luukkonen
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  5. Sari Airaksinen
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  6. Johanna Raiman
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  7. Kaisa Hänninen
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  8. Osmo Antikainen
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  9. Jouko Yliruusi
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Published: October 17, 2001.

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Rantanen, J., Jørgensen, A., Räsänen, E. et al. Process analysis of fluidized bed granulation. AAPS PharmSciTech 2, 21 (2001). https://doi.org/10.1208/pt020421

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  • DOI: https://doi.org/10.1208/pt020421

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