(539f) Continuous Drying of Pharmaceuticals | AIChE

(539f) Continuous Drying of Pharmaceuticals


Kreimer, M. - Presenter, Research Center Pharmaceutical Engineering
Aigner, I., RCPE Gmbh
Sacher, S., RCPE
Krumme, M., Novartis Pharma AG
Mannschott, T., Novartis Pharma AG
van der Wel, P., Hosokawa Micron B.V.
Kaptein, A., Hosokawa Micron B.V.
Khinast, J. G., Research Center Pharmaceutical Engineering
Continuous Drying of Pharmaceuticals

M. Kreimer1, I. Aigner1, S. Sacher1, M. Krumme2, T. Mannschott2, P. van der Wel3, A. Kaptein3, J.G. Khinast1,4

1 Research Center Pharmaceutical Engineering (RCPE) GmbH, Inffeldgasse 13, 8010 Graz, Austria

2 Novartis Pharma AG, Novartis Campus, 4056 Basel, Switzerland

3 Hosokawa Micron B.V., Gildenstraat 26, 7005 BL Doetinchem, Netherlands

4 Graz University of Technology, Institute for Process and Particle Engineering, Inffeldgasse 13, 8010 Graz, Austria

Traditional production of pharmaceutical products has been mostly conducted via batch processing during the last decades. This kind of production is inflexible and involves cost-intensive process development, especially during up-scaling within phases II and III of drug product development. A lot of effort has been made from academia, industry and regulators to overcome these challenges by development of fully continuous manufacturing processes for pharmaceutical goods. This paradigm shift from batch to continuous processing is demanded as more and more NME (new molecule entities) are entering the market and demanding flexible production processes. Furthermore, continuous pharmaceutical manufacturing facilities allow 100% real-time quality assurance and process control. A complete manufacturing line may include very different unit operations starting with API synthesis and ending up with compaction of final tablets. Although a range of manufacturing equipment is available for various unit operations, there is still a gap in linking primary and secondary manufacturing.

Continuous drying of API’s is one of those challenging process steps. Consistent quality of the dried solid product is crucial and has to be maintained after crystallization, washing and filtration. During these processes extensive effort is taken to optimize particle properties such as particle morphology, size or bulk flowabiltiy. Therefore, the particle properties of the intermediates defined and tuned in previous steps have to be at least unaltered during drying or even optimized. This raises several challenges during the drying process of wet powders, because agglomeration and attrition are present permanently as counteracting forces due to shear movement.

Besides matching of specified product quality, the key to successful continuous drying of powders is a robust process design and consistent process ability. These process design considerations include, amongst others, avoiding of dead zones and a narrow residence time distribution. The latter is favorable to avoid mixing of particles with different moisture content and to diminish the tendency of agglomeration or attrition. One approach to avoid those issues is the application of forced-feed.

In this work experiments were conducted on two different drying platform technologies with different model substances, including API’s and excipients with particle sizes below 100 µm. The two investigated drying platforms are based on extrusion and a contact-convective drying technology. Different process settings were investigated and successful configurations achieved. Initial moisture content of the feed material was varied to analyze the drying rate and capacity of the dryers. Measurements were performed for residual moisture content, particle size distribution and flowability and results were compared between raw, wet and dried material. Residual moisture levels below 0.1% were reached. No agglomeration or attrition was observed during the drying procedure as particle size distribution was unchanged for the dried product. Furthermore, similar results were obtained for powder flowability prior and after drying.