Moisture and drug solid-state monitoring during a continuous drying process using empirical and mass balance models

Margot Fonteyne, Delphine Gildemyn, Elisabeth Peeters, Séverine Thérèse F.C. Mortier, Jurgen Vercruysse, Krist Gernaey, Chris Vervaet, Jean Paul Remon, Ingmar Nopens, Thomas De Beer

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Classically, the end point detection during fluid bed drying has been performed using indirect parameters, such as the product temperature or the humidity of the outlet drying air. This paper aims at comparing those classic methods to both in-line moisture and solid-state determination by means of Process Analytical Technology (PAT) tools (Raman and NIR spectroscopy) and a mass balance approach. The six-segmented fluid bed drying system being part of a fully continuous from-powder-to-tablet production line (ConsiGma™-25) was used for this study. A theophylline:lactose:PVP (30:67.5:2.5) blend was chosen as model formulation. For the development of the NIR-based moisture determination model, 15 calibration experiments in the fluid bed dryer were performed. Six test experiments were conducted afterwards, and the product was monitored in-line with NIR and Raman spectroscopy during drying. The results (drying endpoint and residual moisture) obtained via the NIR-based moisture determination model, the classical approach by means of indirect parameters and the mass balance model were then compared. Our conclusion is that the PAT-based method is most suited for use in a production set-up. Secondly, the different size fractions of the dried granules obtained during different experiments (fines, yield and oversized granules) were compared separately, revealing differences in both solid state of theophylline and moisture content between the different granule size fractions.
© 2014 Elsevier B.V. All rights reserved
Original languageEnglish
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Issue number3
Pages (from-to)616–628
Publication statusPublished - 2014


  • NIR spectroscopy
  • Raman spectroscopy
  • Real-time monitoring
  • End-point detection
  • Granule size fractions
  • Fluid bed drying
  • PAT

Cite this

Fonteyne, M., Gildemyn, D., Peeters, E., Mortier, S. T. F. C., Vercruysse, J., Gernaey, K., Vervaet, C., Remon, J. P., Nopens, I., & De Beer, T. (2014). Moisture and drug solid-state monitoring during a continuous drying process using empirical and mass balance models. European Journal of Pharmaceutics and Biopharmaceutics, 87(3), 616–628.