Project Details
Projekt
Model-based quality control in continuous manufacturing of pharmaceutical granules and tablets (QC4CM)
Applicants
Dr. Stefan Klinken-Uth; Dr.-Ing. Sebastian Stemmler
Subject Area
Mechanical Process Engineering
Term
since 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 504702251
The wet granulation and drying process chain is a step in pharmaceutical manufacturing, serving as a bridge between raw material and final oral solid dosage form. Conventionally, this is done in batch processes, whereas the exploration of continuous processes and the real time monitoring and control of critical quality attributes is currently gaining increasing importance. During the first project phase, we developed a Quality by Control concept within a continuous granulation and drying plant. Within this work we aimed for the integration of suitable process analytical technology, expansion of process understanding and the control of critical quality attributes of the finished granules such as particle size distribution and moisture content. Building on the quality-by-control framework for granulate production, the second funding period will focus on the integration of the investigated processes into a continuous process chain for tablet manufacturing. This requires the consideration of both upstream and downstream processes. The former includes continuous dosing and mixing processes, while the downstream involves tablet production from the granules as an intermediate product. The goal is the development of methods to ensure the production of granulates with quality attributes that yield optimal tablet quality. In the context of our research hypothesis, it has to be investigated how variations in the pre-blend composition of the powder, as well as the mass flow rate, affect the granulation and the properties of the tablets. One of the objectives is to maximize product throughput as a part of the overall process optimization. A critical aspect of this phase is the development of advanced experimental design strategies, including automated approaches that efficiently explore the design space while considering processing constraints, which will lead to a reduction in the high experimental effort. In particular, it must be investigated how the properties of the produced granules affect the tableting process and the tablet properties. Of special interest here is the PSD of the granules in relation to die filling during tableting. The gathered data will then be used for cross-process optimization of tablet properties by adjusting granule characteristics. This approach is enabled by the improved closed loop control of granule CQAs, which was developed in the first funding period. By bridging the granulation and tableting process steps, we aim to develop a deep understanding of the entire manufacturing chain and to analyze optimal process control strategies for robust continuous pharmaceutical manufacturing of tablets via wet granulation.
DFG Programme
Priority Programmes
Co-Investigators
Professor Dr. Jörg Breitkreutz; Professorin Dr.-Ing. Heike Vallery
