(509c) Continuous Twin-Screw Powder Feeding – a Crossroad for Continuous Process Development

Continuous
Twin-Screw Powder Feeding – A Crossroad for Continuous Tablet Manufacturing

 T.R. Hörmann^1,2,3, J. Kruisz^1,2, M. Beretta^1,2, E. Faulhammer^1,2,
W.-K. Hsiao^1,2, J.G. Khinast^1,2,3

¹ Research Center Pharmaceutical Engineering GmbH, Graz,
Austria

² European Consortium
for Continuous Pharmaceutical Manufacturing (ECCPM), 8010 Graz, Austria

³ Institute for
Process and Particle Engineering, Graz University of Technology, Graz, Austria

Abstract

Continuous powder feeding is of critical importance during
continuous manufacturing (CM), since it is (next to in-process segregation) the
most susceptible source of content uniformity fluctuations in the final drug
product. While loss-in-weight twin-screw feeding technology is well developed
and a large variety of equipment is available and pharmaceutical powders were
extensively characterized, there is still room for further learnings on the processability
of the pure powders and their respective bends. In order to make an informed
decision on the optimal feeding strategy, i.e., split-feeding of pure materials
vs. pre-blend feeding, critical material/blend attributes must be identified
and considered in context to the available equipment.

This study investigates four pharmaceutical materials in different
grades (in total nine powders) in four twin-screw feeders in different scales. The
combinations of all powders and feeders were characterized in feeding experiments
to elucidate the interaction of equipment and powder with regard to screw
feeding capacity and powder densification and flow in the hopper. Multivariate
data analysis was utilized to identify relevant material descriptors for powder
feeding performance and to establish a model for their processability in
different feeder equipment scales and screws. Thereby, the feeding equipment
was represented by quantitative geometry descriptors in the statistical models.
Moreover, qualitative observations, such as rat-holing, or powder bridging in
the hopper were evaluated to gain deeper insight in events associated with a
failure of the feeding process, that is a lack of material flow into the
screws.

The aim for the statistical model is to predict, for which
combinations of powder properties and feeding equipment geometries well-controlled
continuous feeding can be achieved. Future investigations will expand this
approach to pre-blend feeding, also involving mechanistic modeling methods.

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