Dokument: Enabling end-to-end continuous manufacturing by API suspension feed and instantaneous drying in twin-screw wet granulation

Titel:Enabling end-to-end continuous manufacturing by API suspension feed and instantaneous drying in twin-screw wet granulation
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URN (NBN):urn:nbn:de:hbz:061-20180516-104918-1
Dokumententyp:Wissenschaftliche Abschlussarbeiten » Dissertation
Autor: Schmidt, Adrian [Autor]
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Dateien vom 14.05.2018 / geändert 14.05.2018
Beitragende:Prof. Dr. Dr. hc. Kleinebudde, Peter [Gutachter]
Prof. Dr. Breitkreutz, Jörg [Gutachter]
Stichwörter:twin-screw wet granulation, continuous manufacturing, tableting, API suspension feed
Dewey Dezimal-Klassifikation:600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit
Beschreibung:For decades, medicine has been manufactured in batch processes in pharmaceutical industries. However, current manufacturing practices are inefficient and hence not sustainable and competitive on the long term. One emerging technology that is under investigation to achieve cleaner, flexible and more efficient manufacturing processes is continuous manufacturing. In continuous manufacturing materials are charged continuously into, and products are discharged continuously from the manufacturing process, i.e. “one in, one out”. There are different levels of the integration of continuous manufacturing that can be distinguished, e.g. partial integration of multiple connected unit operations, chain integration for chemical or pharmaceutical manufacturing lines, or full integration of all unit operations into a single end-to-end continuous manufacturing line.
This thesis focusses on enabling end-to-end continuous manufacturing of pharmaceuticals/drug products for a wet granulation process. This was done by removal of the typical last drug substance manufacturing step (drying) and feeding the drug substance suspended in the washing liquid in a twin-screw granulator. The washing liquid was used directly as a granulation liquid. The drug substance suspension feed in twin-screw wet granulation thereby represents the interface between chemical and pharmaceutical manufacturing in a possible configuration of an end-to-end continuous manufacturing process. In terms of granule and subsequent tablet quality it was shown, that feeding the drug substance as a suspension is comparable to the traditional drug substance blend feed in twin-screw wet granulation. Such approach does not only enable linking drug substance and drug product manufacture, but also improves process efficiency by removal of a manufacturing step (drying).
As a consequence of omitting previous drying steps and the use of the original solvent for granulation, more extensive drying is required after twin-screw wet granulation. However, it has been demonstrated, that twin-screw wet granulation and drying can be combined in one single process step enabling further simplification of pharmaceutical continuous manufacturing. The so-called ‘in-barrel-drying’ uses the segmented temperature control of barrel zones of the twin-screw granulator. One compartment of the equipment is operated at relatively low temperatures to perform wet granulation and to heat up the material, whereas a second compartment is operated at very high temperatures to perform instantaneous drying. It was shown, that indeed dried granules of good quality could be obtained that could be used for compression.
When combining the drug substance suspension feed and in-barrel-drying concepts, two drying steps (before and after wet granulation) can be omitted in a possible configuration of a fully integrated end-to-end continuous process chain. Hence, this approach is a significant simplification in the continuous manufacturing by removal of time-intensive and expensive drying steps. Thereby this thesis could contribute significantly to the development of sustainable and competitive end-to-end continuous manufacturing for wet granulation processes.
Lizenz:In Copyright
Fachbereich / Einrichtung:Mathematisch- Naturwissenschaftliche Fakultät » WE Pharmazie » Pharmazeutische Technologie und Biopharmazie
Dokument erstellt am:16.05.2018
Dateien geändert am:16.05.2018
Promotionsantrag am:18.12.2017
Datum der Promotion:20.02.2018
Status: Gast