Dokument: Multi-resonance Microwave Sensors for Moisture Monitoring in Fluid-bed Processes
| Titel: | Multi-resonance Microwave Sensors for Moisture Monitoring in Fluid-bed Processes | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=50836 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20190916-090518-3 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Peters, Johanna [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Breitkreutz, Jörg [Betreuer/Doktorvater] Prof. Dr. Kleinebudde, Peter [Gutachter] | |||||||
| Stichwörter: | PAT, Wirbelschicht, Fluid-bed, Granulation | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
| Beschreibungen: | Im Rahmen der vorliegenden Arbeit wurden neuartige Mikrowellenresonanzsensoren als PAT-Werkzeug für die Feuchtemessung in pharmazeutischen Wirbelschichtprozessen untersucht. Während das Verfahren bereits häufig z.B. in der Nahrungsmittel- und in der holzverarbeitenden Industrie eingesetzt wird, ist es im pharmazeutischen Bereich noch eine in der Entwicklung befindliche Technologie, deren Anwendung in den letzten Jahren stagnierte.
Zusammenfassend bestätigen die Resultate dieser Dissertation, dass mit Hilfe mehrfrequenter Mikrowellenresonanzsensoren sowohl off-line und at-line als auch in-line zuverlässig die Restfeuchte von Schüttgütern bestimmt werden kann. Darüber hinaus erlaubten Untersuchungen an Rohdaten, die Schwächen vorheriger Systeme zu erkennen und den im Vergleich zu vorherigen Sensoren deutlich ausgeweiteten Messbereich eindeutig einzugrenzen. Durch die Verwendung gleichartiger Sensoren in verschiedenen Gerätetypen konnte der Nutzen des neuartigen Messsystems als PAT-Werkzeug bestätigt werden. Zuverlässige Auswertemethoden konnten etabliert werden.In the present thesis, the application of novel microwave resonance technology sensor systems as a PAT tool for moisture measurement within pharmaceutical fluid-bed granulation and drying processes was studied. Microwave resonance technology is commonly employed for moisture measurements in the food and wood processing industries but still emerging within the pharmaceutical sector. Single-resonance sensor systems were introduced a decade ago but exhibited deficient performance at moisture ranges higher than 8 %. Within this thesis, a novel multi-resonance microwave sensor aiming to overcome these issues was investigated. For the first time within the pharmaceutical sector, raw resonance curves were recorded and evaluated at various moisture levels. A link between the absence of further attenuation resp. relative widening of the resonance curve and a non-linear increase in microwave moisture values at higher moistures could be established. This off-line characterization revealed that measurable ranges depend on the employed resonance frequency and the material under test. Additionally, it provided a sound basis for off-line measurements on granule samples of up to approx. 20 % residual moisture content conducted during a successful method validation according to ICH guideline Q2(R1). In a further step, sensor application for process monitoring was tested. Therefore, the temperature compensation was verified within different scale granulators, the measurement rate was accelerated, and a sliding average window was applied to measured frequencies and bandwidths in order to compensate for random fluctuations caused by varying material coverage. Based on the equipment design, necessary modifications of the sensor system and mounting position could be identified and made. Evaluation models covering all moisture contents occurring during the respective granulation processes (up to 16 %) could be successfully developed, compared with different chemometric approaches, and validated. To prove the applicability of multi-resonance microwave sensors independent of the process parameters and formulation, an experimental design on real-life formulations containing donepezil hydrochloride as active pharmaceutical ingredient and lactose monohydrate as crystal-water containing excipient was successfully performed. Finally, one of the novel sensor prototypes was tested in a semi-continuous fluid-bed dryer. Proof-of-concept could be provided without further adaptations of the sensor head or position and the first comparative in-line study between microwave sensors and near-infrared spectroscopy revealed that, in particular, the simple calibration makes multi-resonance microwave sensor systems a valuable alternative. In all cases, the in-depth investigations of deficiencies of previous systems based on raw resonance curves enabled a thorough understanding and a reliable identification of the measurement range, which was significantly extended as compared with previous systems, and simple and reliable data evaluation methods were established. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Pharmazie » Pharmazeutische Technologie und Biopharmazie | |||||||
| Dokument erstellt am: | 16.09.2019 | |||||||
| Dateien geändert am: | 16.09.2019 | |||||||
| Promotionsantrag am: | 01.04.2019 | |||||||
| Datum der Promotion: | 10.05.2019 |
