(26c) Vibratory Mixing of Pharmaceutical Powders on a Single-Tablet-Scale

While many things change in pharmaceutical industry, tablets remain the most important way of administering Active Pharmaceutical Ingredients (APIs) to a patient. Due to the high production volume, tablets are usually produced in highly optimized processes for fixed doses, dependent on complex supply chains. Security of the supply chain, as well as an observable trend to patient-tailored medicines, call for more flexible production options.

To meet these needs, we aim to develop a small-scale production system for individual tablets. In this context, composition, mixing procedure and compaction step can be adjusted for every single tablet. Such a device will be a powerful tool to cope with the above-mentioned challenges, and furthermore, speed up formulation and process development for new drug products, in the context of translational pharmaceutics.

The system we have designed is based on a single tablet direct compression process, consisting of gravimetric dosing, followed by vibratory mixing and compaction. In our talk we will answer the question of how to set up a vibratory mixing process, to achieve a sufficiently well-mixed powder blend within a reasonable time, i.e., below 10 seconds. An experimental setup is presented which allows to continuously monitor the mixing quality of a 400 mg powder bulk during the mixing process, using highspeed camera image analysis. The vibratory motion is created by an electrodynamic shaker capable of supplying accelerations of up to 100 G for the used setup.

Two microcrystalline cellulose fillers were used as model substances. Virgin Emcocel 90 M having an average particle size of 130 µm, showing slightly cohesive behavior due to its particle shape, and dyed Avicel PH-102 with an average particle size of 100 µm and free-flowing characteristics. The container used as mixing vessel had an inner diameter of 10 mm and a height of 28 mm. Applied frequencies ranged from 100 to 300 Hz and led to different flow patterns within the mixing container, and therefore to different mixing times. Results on the mixing efficiency will be presented.