In-line moisture monitoring in fluidized bed granulation using a novel multi-resonance microwave sensor

Johanna Peters; Kathrin Bartscher; Claas Döscher; Wolfgang Taute; Michael Höft; Reinhard Knöchel; Jörg Breitkreutz

doi:10.1016/j.talanta.2017.03.105

In-line moisture monitoring in fluidized bed granulation using a novel multi-resonance microwave sensor

Talanta. 2017 Aug 1:170:369-376. doi: 10.1016/j.talanta.2017.03.105. Epub 2017 Apr 5.

Authors

Johanna Peters¹, Kathrin Bartscher², Claas Döscher³, Wolfgang Taute⁴, Michael Höft⁴, Reinhard Knöchel⁴, Jörg Breitkreutz⁵

Affiliations

¹ Heinrich-Heine-University Düsseldorf, Institute of Pharmaceutics and Biopharmaceutics, Düsseldorf, Germany; NextPharma Waltrop, Pharbil Waltrop GmbH, Waltrop, Germany. Electronic address: johanna.peters@hhu.de.
² NextPharma Waltrop, Pharbil Waltrop GmbH, Waltrop, Germany.
³ Döscher Microwave Systems GmbH, Hamburg, Germany.
⁴ Christian-Albrechts-University Kiel, Institute of Electrical Engineering and Information Technology, Kiel, Germany.
⁵ Heinrich-Heine-University Düsseldorf, Institute of Pharmaceutics and Biopharmaceutics, Düsseldorf, Germany.

PMID: 28501183
DOI: 10.1016/j.talanta.2017.03.105

Abstract

Microwave resonance technology (MRT) is known as a process analytical technology (PAT) tool for moisture measurements in fluid-bed granulation. It offers a great potential for wet granulation processes even where the suitability of near-infrared (NIR) spectroscopy is limited, e.g. colored granules, large variations in bulk density. However, previous sensor systems operating around a single resonance frequency showed limitations above approx. 7.5% granule moisture. This paper describes the application of a novel sensor working with four resonance frequencies. In-line data of all four resonance frequencies were collected and further processed. Based on calculation of density-independent microwave moisture values multiple linear regression (MLR) models using Karl-Fischer titration (KF) as well as loss on drying (LOD) as reference methods were build. Rapid, reliable in-process moisture control (RMSEP≤0.5%) even at higher moisture contents was achieved.

Keywords: Fluid bed granulation; Granule moisture; In-line moisture measurement; Microwave resonance technology; Multivariate data analysis; Process analytical technology (PAT).