Continuous feeding of low-dose APIs via periodic micro dosing

Abstract

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.

Comparison between integrated continuous direct compression line and batch processing – The effect of raw material properties

“…Solutions for stable feeding of very small amounts have been previously introduced e.g. in the publications of Besenhard et al (Besenhard et al, 2017(Besenhard et al, , 2016. Particle engineering has also been postulated as a means to ensure a proper content uniformity with low drug load formulations (Sun et al, 2017).…”

Improving blend content uniformity via dry particle coating of micronized drug powders

“…Further, the accurate feeding protocols for a small portion of materials are also important for obtaining acceptable low dose blend uniformity. For example, various methods such as periodic micro dosing are investigated which are especially beneficial for continuous manufacturing (Besenhard et al, 2016). In this work, which was performed at small batch scales, the small amount of the API is directly weighed, hence no feeding issues were encountered and are not specifically considered.…”

A multivariate approach to predict the volumetric and gravimetric feeding behavior of a low feed rate feeder based on raw material properties

“…Developing such predictive models is especially relevant for low feed rate feeders as these feeders are generally used for low-dosed raw materials (e.g., APIs). In addition, the growing interest within the pharmaceutical industry for high-potency active pharmaceutical ingredients further encourages the need of a predictive platform for these types of feeders (Besenhard et al, 2016).…”