Continuous feeding of low-dose APIs via periodic micro dosing.

Precise and effective feeding of small powder quantities remains a challenge in many fields, including pharmaceutical development and production. This paper demonstrates that a simple feeding principle can be applied to accomplish stable micro feeding (<100mg/s) and describes a gravimetric powder feeding system with a vibratory sieve mounted on a chute. Feeding was induced via vertical vibrations that can be adjusted within a broad range of frequencies and amplitudes. The feeding system was studied using different frequencies, amplitudes, sieves and powder properties. Feeding was characterized by means of a dynamic scale and high-speed camera recordings. The feeding system provided effective powder feeding even in a range of 1-2mg/s. It was shown that powder properties require special attention when the vibratory sieve-chute system operates at higher feed rates (or feeding times >30min), i.e., feeding at a higher throughput. A combination of discrete element method (DEM) simulations and compartment population balance model (PBM) was used to incorporate the proposed micro feed system into a continuous powder mixer (Gerike GCM250; Gerike Holding LTD., Regensdorf, Switzerland). It illustrates how oscillating feeding rates (the latter is a characteristic of the studied micro feeding system) affect the content uniformity of low dose blends, i.e., powder mixtures with a relatively low fraction of active pharmaceutical ingredient.