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Moisture and drug solid-state monitoring during a continuous drying process using empirical and mass balance models.
Eur J Pharm Biopharm. 2014 Aug; 87(3):616-28.EJ

Abstract

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.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Fonteyne M
Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium. Electronic address: Margot.Fonteyne@Ugent.be.
Gildemyn D
Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium.
Peeters E
Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
Mortier ST
BIOMATH, Department of Mathematical Modelling, Statistics and Bioinformatics, Ghent University, Ghent, Belgium.
Vercruysse J
Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
Gernaey KV
Department of Chemical and Biochemical Engineering, Technical University of Denmark, Lyngby, Denmark.
Vervaet C
Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
Remon JP
Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
Nopens I
BIOMATH, Department of Mathematical Modelling, Statistics and Bioinformatics, Ghent University, Ghent, Belgium.
De Beer T
Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium. Electronic address: Thomas.DeBeer@Ugent.be.

MeSH

CalibrationChemistry, PharmaceuticalHumidityLactoseMolecular WeightPharmaceutical PreparationsPolyvinylsPowdersPyrrolidinesSpectroscopy, Near-InfraredSpectrum Analysis, RamanTabletsTechnology, PharmaceuticalTemperatureTheophylline

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24613541

Citation

Fonteyne, Margot, et al. "Moisture and Drug Solid-state Monitoring During a Continuous Drying Process Using Empirical and Mass Balance Models." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 87, no. 3, 2014, pp. 616-28.
Fonteyne M, Gildemyn D, Peeters E, et al. Moisture and drug solid-state monitoring during a continuous drying process using empirical and mass balance models. Eur J Pharm Biopharm. 2014;87(3):616-28.
Fonteyne, M., Gildemyn, D., Peeters, E., Mortier, S. T., Vercruysse, J., Gernaey, K. V., 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 : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 87(3), 616-28. https://doi.org/10.1016/j.ejpb.2014.02.015
Fonteyne M, et al. Moisture and Drug Solid-state Monitoring During a Continuous Drying Process Using Empirical and Mass Balance Models. Eur J Pharm Biopharm. 2014;87(3):616-28. PubMed PMID: 24613541.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Moisture and drug solid-state monitoring during a continuous drying process using empirical and mass balance models. AU - Fonteyne,Margot, AU - Gildemyn,Delphine, AU - Peeters,Elisabeth, AU - Mortier,Séverine Thérèse F C, AU - Vercruysse,Jurgen, AU - Gernaey,Krist V, AU - Vervaet,Chris, AU - Remon,Jean Paul, AU - Nopens,Ingmar, AU - De Beer,Thomas, Y1 - 2014/03/05/ PY - 2013/12/21/received PY - 2014/02/24/revised PY - 2014/02/27/accepted PY - 2014/3/12/entrez PY - 2014/3/13/pubmed PY - 2015/3/10/medline KW - End-point detection KW - Fluid bed drying KW - Granule size fractions KW - NIR spectroscopy KW - PAT KW - Raman spectroscopy KW - Real-time monitoring SP - 616 EP - 28 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 87 IS - 3 N2 - 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. SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/24613541/Moisture_and_drug_solid_state_monitoring_during_a_continuous_drying_process_using_empirical_and_mass_balance_models_ DB - PRIME DP - Unbound Medicine ER -