(75e) A Two-Dimensional PBM for Continuous Drying of a Population of Granules Including Drying and Breakage

The continuous production of pharmaceutical tablets is the result of different consecutive continuous sub-processes. The use of a wet granulation technique during tablet production requires the subsequent drying of the wet granules. This can be achieved using several techniques, which choice potentially influences the properties of the granules and, hence, their further downstream processing. In this work, a six-segmented fluidized bed dryer, which is part of a full continuous from-powder-to-tablet line, i.e. the ConsiGma^TM (GEA Pharma Systems), is studied.

The development of mechanistic models is increasingly important, especially in view of the transition from batch to continuous production processes and its accompanied need for improved process understanding. Models play a significant role in the latter as they facilitate process analysis, optimization and control strategy development.

Models for granule drying have been developed. However, during the fluidized bed drying process, granules are prone to break up potentially resulting in smaller sized granules. The simultaneous process of breakage and drying can be modeled using a Population Balance Model (PBM). The latter allows analysing particles that interact with each other as well as the continuous phase. A one-dimensional PBM describing the evolution of the moisture content distribution during drying was developed in previous research. In this contribution, this model has been extended towards a two-dimensional PBM. This model allows predicting the evolution of the joint granule size and moisture content distribution during drying. Two different breakage mechanisms were implemented, i.e. granule breakage and surface erosion. Whereas in the first case two or more smaller particles are formed with a noticeable size, in the latter case fine dust is formed while the size of the mother particle remains almost identical. Several mechanisms have been theoretically investigated, i.e. erosion, the formation of two equal fragments, etc. Another important aspect is the rate of breakage. Both the breakage rate and the breakage mechanism will be influenced by several process conditions. The gas velocity during fluidization potentially has an impact on the breakage rate, where a higher gas velocity could increase the breakage rate. Furthermore, it can be expected that particles with a lower moisture content will be more prone to erosion compared to wetter particles. The form and the size of the particles will both influence the rate and the mechanism of breakage. Spherical particles are less prone to breakage compared to elongated particles.

In this study, the breakage behaviour during drying has been investigated theoretically by simulating the PBM for different breakage mechanisms and rates. The effect of the parameters in the kernels has been analysed in detail. Experimental investigation and validation is the next step in the research but not included in this work.