Dokument: Hybrid Modelling of Roll Compaction
| Titel: | Hybrid Modelling of Roll Compaction | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=56578 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20220701-102648-4 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Keizer, Hannah Lou [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Kleinebudde, Peter [Gutachter] Prof. Dr. Breitkreutz, Jörg [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibung: | Roll compaction/dry granulation is an important process in the pharmaceutical industry for the production of solid dosage forms containing, e.g., heat- or moisture-sensitive excipients or APIs. In the early phase of formulation development, new chemical entities are often expensive and only available in limited quantities, so that simulation of the process offers advantages.
The aim of this work is to develop a time and material saving method for the mimicking and simulation of the roll compaction process with a uniaxial compaction simulator (Styl’One Evolution, Medelpharm). The solid fraction (SF) is the comparative critical attribute for ribbons and mimicked ribbons (ribblets). In this context, the elastic recovery of ribblets after compression is also to be considered for the calculation of their SF. A deeper understanding of roll compaction should be gained by investigating the influence of process parameters and machine design on the ribbon quality. A method to estimate the nip angle with the uniaxial compaction simulator is to be developed. Finally, the whole downstream process - from preparation of the powder blend, through roll compaction and granulation to tableting - is to be mimicked and compared with roll compaction/dry granulation. The hybrid modelling approach combines uniaxial tableting experiments with model calculations to simulate the roll compaction process. For the mimicking, flat faced rectangular punches are used, which represent the roll surface. The punch movement, which has a rounded profile imitating the rolls, corresponds to the roll diameter and roll speed. The minimum distance between the upper and the lower punch during compression corresponds to the gap width (GW). The mathematical model is based on dividing the powder bed into infinitely thin layers and integrating the forces acting on the material during the compaction process. The compression pressure (CP) on the compaction simulator can be converted into the specific compaction force (SCF) on the roll compactor. To obtain ribbons and ribblets with the same SF, this relationship must be adapted by applying correction factors (Kp factor), which were determined experimentally. Hybrid modelling was validated with data from roll compaction using microcrystalline cellulose, lactose monohydrate and dibasic calcium phosphate anhydrate on four roll compactors, which differ in their machine design regarding roll configuration, roll diameter, roll width, feeding- and sealing-system (Mini-Pactor, BRC25, WP120, WP200). The influence of several process parameters on the SF, which is determined by helium and powder pycnometry, was evaluated. A method was developed to determine the axial elastic recovery of ribblets in-die by measuring the distance between upper and lower punch when the force on the upper punch decreases to zero in its upward movement after compression. The out-of-die elastic recovery of ribblets was investigated by chromatic confocal measurements. A simple method to estimate the nip angle was established by using the distance between upper and lower punch when the force on the upper punch starts to increase considerably and the minimum distance between the punches. The process parameters for roll compaction were determined by hybrid modelling for a formulation containing hydrochlorothiazide as model API. Ribbons and ribblets were granulated. Tablets were produced at five different CP from uncompacted powder mixture, ribbon granules and ribblet granules. Kp factors for the different roll compactors were determined. For the Mini-Pactor and the BRC25, Kp factors of 0.667 and 0.714, respectively, were found, which are independent of the material and the process parameters (GW, SCF), at least in the investigated design space. The experiments with the WP120 and the WP200 indicate that roll-speed, -diameter, -width, -surface and the feeding system influence the Kp factor since their effect cannot be covered by the uniaxial mimicking. However, it is possible to produce ribbons and ribblets with the same SF, once the Kp factors are established. Interestingly, the same simulated SCF does not correspond to the same CP when the GW is varied. Independent of the GW and independent on the simulated compactor, the same SF resulted when the same CP were applied to the same material. This leads to the assumption that it is not the SCF but the resulting maximum roll pressure which is the decisive factor for the ribbon SF. It was found that the elastic recovery is dependent on the CP, the die filling height/GW and that a big part of the elastic recovery is completed within seconds after ejection. The implementation of the elastic recovery measurement to the simulation software allowed to optimise the predictive capability of the model for the ribblet SF. The dependence of the nip angle on material properties and process parameters was investigated. Positive effects on the nip angle were found for the GW, the SCF and the Hausner ratio of the materials, which is in accordance with the literature. In a next step, the method should be verified with roll compaction experiments. Regarding the downstream process, the properties of the intermediates and the final tablets were evaluated to assess the performance of the modeling approach. The ribbon and ribblet SF are similar, but the granule size distribution differs in the fraction of fines. However, the properties - tensile strength, disintegration - of the final tablets produced from ribbon and ribblet granules are similar. It was shown that it is possible to determine the required process parameters for roll compaction by hybrid modelling with only a small amount of material (< 5 g) and that mimicking the downstream process results in tablets with similar properties. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Pharmazie » Pharmazeutische Technologie und Biopharmazie | |||||||
| Dokument erstellt am: | 01.07.2022 | |||||||
| Dateien geändert am: | 01.07.2022 | |||||||
| Promotionsantrag am: | 13.03.2021 | |||||||
| Datum der Promotion: | 21.05.2021 |
