Development of a Controlled Continuous Low-Dose Feeding Process

• Published in: AAPS PharmSciTech Vol. 22; no. 7; p. 247
• Main Authors: Fathollahi, Sara, Kruisz, Julia, Sacher, Stephan, Rehrl, Jakob, Escotet-Espinoza, M. Sebastian, DiNunzio, James, Glasser, Benjamin J., Khinast, Johannes G.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 12.10.2021
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Pharmacology/Toxicology; Pharmacy; Powders; Research Article; Technology, Pharmaceutical; Loss-in-weight feeder; Low dose feeding; Feed forward control; Continuous feeding; Iterative learning control
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-021-02104-9

This paper proposes a feed rate control strategy for a novel volumetric micro-feeder, which can accomplish low-dose feeding of pharmaceutical raw materials with significantly different powder properties. The developed feed-forward control strategy enables a constant feed rate with a minimum deviation from the set-point, even for materials that are typically difficult to accurately feed (e.g., due to high cohesion or low density) using conventional continuous feeders. Density variations observed during the feeding process were characterized via a displacement feed factor profile for each powder. The characterized effective displacement density profile was applied in the micro-feeder system to proactively control the feed rate by manipulating the powder displacement rate (i.e., computing the feed rate from the powder displacement rate). Based on the displacement feed factor profile, the feed rate can be predicted during the feeding process and at any feed rate set-point. Three pharmaceutically relevant materials were used for the micro-feeder evaluation: di-calcium phosphate (large-particle system, high density), croscarmellose sodium (small-particle system, medium density), and barium sulfate (very small-particle <10 μm, high density). A significant improvement in the feeding performance was achieved for all investigated materials. The feed rate deviation from the set-point and its relative standard deviation were minimal compared to operations without the control strategy.