ISBN 9783843950503

978-3-8439-5050-3, Reihe Ingenieurwissenschaften

Claas Steenweg
Design, Characterization, and Operation of a Modular Continuous Vacuum Screw Filter

139 Seiten, Dissertation Technische Universität Dortmund (2022), Softcover, A5

Zusammenfassung / Abstract

Integrated continuous manufacturing processes of active pharmaceutical ingredients (APIs) provide key benefits concerning product quality control, reduced time‑to‑market, steady-state operation, and scale‑up capability. Thereby, the crystallization step, which is used in 90 % of all API processes, mainly defines the final particle properties. However, the industrial application of continuous manufacturing often cannot succeed because it lacks of small-scale equipment for continuous crystallization and particle isolation. The scope of this thesis is to address these issues. Therefore, the concept of the modular continuous vacuum screw filter (CVSF) was invented, the prototype designed, built and characterized, and the idea patented. The overall goal is to obtain dried and free-flowing product particles continuously from the fed suspension, by means of integrated filtration, washing, and drying in a flexible and modular set-up.

A model system (L-alanine/water) with comparable particulate properties as higher-priced APIs was used demonstrating that the inlet particle size distribution (PSD) can be entirely maintained while ensuring a narrow residence time distribution of the solid phase. The operation was possible over 8 h without any clogging issues and free-flowing particles with residual moistures of approx. 1 % were reproducibly obtained. Also for higher aspect ratio particles (e.g. needles), the preservation of product quality and prevention of attrition, breakage, and agglomeration was possible. In a concluding step, a full continuous integrated process was developed combining a continuous slug-flow crystallizer with particle isolation using the CVSF. Summarizing, the CVSF offers unique features, such as its modularity and rapid start-up behavior, providing a promising concept for small-scale continuous particle isolation to address the key barriers for integrated continuous manufacturing processes of APIs.