Dokument: Transfer of twin-screw granulation processes and predictions of barrel fill
| Titel: | Transfer of twin-screw granulation processes and predictions of barrel fill | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=60286 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20220802-111901-2 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Pohl, Sebastian [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Dr. h.c. Kleinebudde, Peter [Gutachter] Prof. Dr. Breitkreutz, Jörg [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibung: | The successful prediction of optimal liquid-to-solid (L/S) ratios for wet granulation has been described in the literature for high-shear granulation (HSG) processes. Therefore, this promising approach should be tested for twin-screw granulation (TSG). For this purpose, a formulation was first investigated using a mixer torque rheometer (MTR) to determine its interaction with the liquid phase by measuring the torque values at increasing liquid contents and thereby calculate the optimal L/S ratio, which was assumed to be at the inflection point of the second derivative of the torque curve. Verification of the predicted L/S ratios showed that the concept suitable for HSG could not be transferred to TSG. The screws of the granulator exerted a much higher stress on the wet mass than the kneaders of the MTR, which might lead to higher degrees of saturation at defined L/S ratios. This promoted the formation of undesirably large granules on the granulator, as there was presumably more liquid available for granule growth in the intergranular voids compared to the MTR. It was concluded that the L/S ratio on the twin-screw granulator should be much lower than the L/S ratio at the inflection point defined on the MTR.
Another objective was the development of an approach to quantify screw configurations as single shear stress values, considering each element of the screw design and the actual process parameters. Several studies were carried out in which the tip speeds and barrel fill levels were kept similar on different granulators. Even though comparable granule and tablet characteristics were produced using different granulators, some very large deviations were calculated for the shear stresses using the new approach. These deviations would imply different stresses acting on the wet mass, which is why differences in the properties of granules and tablets could be expected. Since this was not the case, the newly created approach was therefore not as useful as initially expected. The approach does not adequately reflect the process conditions inside the barrel. Although several surrogates and dimensionless attempts have already been proposed for determining the barrel fill level at given process parameters, none of them considers the real screw configuration and the materials conveying velocity in the barrel. Thus, a new approach was developed which is able to predict both the material hold-ups and residence times. Several studies were conducted with various formulations, screw configurations and process parameters to compare measured and predicted values. The results were used together with literature data to improve model predictability by applying non-linear fits. Compared to the published attempts, the new model has taken a step forward, but further experiments with other formulations, screw configurations and granulators are required to extend the validity of the model. Since the level of knowledge in TSG is not yet sufficient for a regime map, parameters that might be suitable for its creation were compiled and critically assessed at the end of this thesis. In a regime map, dimensionless groups would be formed by correlating input parameters that mainly affect the process with the output parameters, e.g. granule properties, and using them to create an operation window. Once validated, the regime map could help in the development of suitable formulations and TSG processes and reduce both the materials required and the cost of process development. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Pharmazie » Pharmazeutische Technologie und Biopharmazie | |||||||
| Dokument erstellt am: | 02.08.2022 | |||||||
| Dateien geändert am: | 02.08.2022 | |||||||
| Promotionsantrag am: | 27.04.2022 | |||||||
| Datum der Promotion: | 07.07.2022 |
