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Particle Size, Moisture, and Fluidization Variations Described by Indirect In-line Physical Measurements of Fluid Bed Granulation

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Abstract

The aim of this study was to evaluate an instrumentation system for a bench scale fluid bed granulator to determine the parameters expressing the changing conditions during the spraying phase of a fluid bed process. The study focused mainly on four in-line measurements (dependent variables): fluidization parameter (calculated by inlet air flow rate and rotor speed), pressure difference over the upper filters, pressure difference over the granules (lower filter), and temperature of the fluidizing mass. In-line particle size measured by the spatial filtering technique was an essential predictor variable. Other physical process measurements of the automated granulation system, 25 direct and 12 derived parameters, were also utilized for multivariate modeling. The correlation and partial least squares analyses revealed significant relationships between various process parameters highlighting the particle size, moisture, and fluidization effect. Fluidization parameter and pressure difference over upper filters were found to correlate with in-line particle size and therefore could be used as estimates of particle size during granulation. The pressure difference over the granules and the temperature of the fluidizing mass expressed the moisture conditions of wet granulation. The instrumentation system evaluated here is an invaluable aid to gaining more control for fluid bed processing to obtain repeatable granules for further processing.

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Acknowledgements

This work was financially supported by the Finnish Funding Agency for Technology and Innovation TEKES and the Academy of Finland. Ritva Haikala and Henri Salokangas from Orion Pharma are acknowledged for contributing to this study.

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Authors and Affiliations

  1. Orion Corporation Orion Pharma, Orionintie 1, P.O. Box 65, 02101, Espoo, Finland

    Tanja Lipsanen & Tero Närvänen

  2. Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, 00014, Helsinki, Finland

    Heikki Räikkönen, Osmo Antikainen & Jouko Yliruusi

Authors
  1. Tanja Lipsanen
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  2. Tero Närvänen
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  3. Heikki Räikkönen
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  4. Osmo Antikainen
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  5. Jouko Yliruusi
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Correspondence to Tanja Lipsanen.

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Lipsanen, T., Närvänen, T., Räikkönen, H. et al. Particle Size, Moisture, and Fluidization Variations Described by Indirect In-line Physical Measurements of Fluid Bed Granulation. AAPS PharmSciTech 9, 1070–1077 (2008). https://doi.org/10.1208/s12249-008-9147-4

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  • DOI: https://doi.org/10.1208/s12249-008-9147-4

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