(408b) Influence of the Feed Frame Design on a Continuous Manufacturing Process

The pharmaceutical industry is moving towards continuous manufacturing to replace traditional batch production. One example of a continuous direct compaction process is powder feeders that dispense materials into a blender upstream of a tablet press. Although the feeders dispense materials accurately and precisely, small variations in the raw materials or the performance of the feeders can cause small variations in the composition of the powder blend.

The purpose of the blender is to provide a homogeneous material mixture, but it is well known that considerable mixing can occur also in the tablet press. In order to understand the degree of mixing that occurs in the tablet press, DEM simulations of different feed frames are carried out. The focus is on the material flow in the feed frame and into the dies, not the compression step itself. The DEM simulations use a DEM model with calibrated material parameters of a real powder blend; this calibration routine is described in [1,2], where it has been successfully validated for a continuous mixing process.

DEM simulations are carried out for a range of feed frame designs. In addition to providing the residence time distribution (RTD), the results from the DEM simulations show how the material flows in the feed frame and provide an understanding of how each feed frame should be modeled in terms of reduced-order models that accurately capture the dynamics when the holdup mass can vary.

The reduced-order models for the feed frames are then used to show how the mixing characteristics of typical mixers can be used to specify requirements on the feeders. Or alternatively, it is shown how the feeding performance of typical feeders affect the required performance of the mixer. Since the reduced order model properly accounts for a varying holdup mass, particular emphasis is put on identifying combinations of mixers and feed frames that not only are able to handle feeder fluctuations but that also minimized material losses during startup and shutdown.

REFERENCES

[1] Toson et al., 2018. "Detailed modeling and process design of an advanced continuous powder mixer". Int J Pharm 552, 288–300. https://doi.org/10.1016/j.ijpharm.2018.09.032

[2] Toson et al. "Continuous Powder Mixing Technology: Validation of the DEM Model". Submitted to J Pharm Sci.