(201f) Experimental and Theoretical Considerations of a Modular Concept for Continuous Mixing of Pharmaceuticals

Known solids in this field are all based on a vessel with paddle-like agitator in which product is continuously filled to a certain level and where it is being mixed with typical mixing times of several minutes. The residence time is controlled by the level of product in the mixer and the feed capacity. The large quantity of product in the mixer limits the responsiveness to product variations and process variations, thus limiting flexibility of the system.

In this paper these disadvantages are eliminated by introducing the Modulomix.

This unique mixer concept is characterised by two vital qualities: an instant mixing pattern allowing for extremely small quantities of material being present in the mixer during processing and a modular mixer concept where single units can be coupled for obtaining multiple mixing process steps.

Instant mixing in the Modulomix is achieved by the optimal design of the flow pattern of the material in the mixer combined with an intensive mixing mechanism. The mixing zone in the mixer is located in an annulus close to the wall, actually only of a few millimetres thickness. This principle leads to a very dynamic and precise mixing of the components. Residence times are typically in a range between 5 and 15 seconds. This can be achieved by.

The small quantity of material in the mixer effectively increases the responsiveness of the mixing process and decreasing the losses at the beginning and the end of the mixing process.

Of course the short residence times and small quantities of product present in the mixer make the feeding a critical issue especially at low dosing rates of the small, active components.

While keeping the short residence time in the mixer the mixing intensity can be controlled and adjusted by the speed of the rotor, tip speeds typically vary between 2 and 20 m/s. High tip speeds, high mixing intensities are applied for the mixing of the usually fine and cohesive active components and carriers like lactose. Lubricants on the other hand like Magnesium Stearate need to be mixed very gentle at the lowest speeds.

In order to further improve the understanding of this unique mixing technology the experimental results have been compared with an Axial Dispersion model. Based on the results with pulse experiments the functioning of the machine could be well described with a residence time and a Peclet number. Once the these characteristics are determined it is shown to be possible to accurately predict the mixing performance of the Modulomix with realistic feeders.

By combining several units in series, operating at different speeds multiple mixing steps can be achieved. The design of inlet and outlet ports enables a smooth flow of material from one mixer to the other. In between feeding of additional components is possible by the second inlet port on each unit.

The current unit is designed for a typical capacities of 10-100 kg/hour, fitting most tablet presses for in-line production. For off-line situations or for mixing before compacting larger capacities can be used. Scaling of larger production units is possible while maintaining the dynamic properties of the machine.