title: 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.
authors.affiliation: Research Center Pharmaceutical Engineering (RCPE) GmbH, 8010 Graz, Austria.
authors.forename: M O
authors.initials: MO
authors.lastname: Besenhard
authors.affiliation: Rutgers University, Department of Chemical & Biochemical Engineering, NJ, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Karkala
authors.affiliation: Research Center Pharmaceutical Engineering (RCPE) GmbH, 8010 Graz, Austria.
authors.forename: E
authors.initials: E
authors.lastname: Faulhammer
authors.affiliation: Research Center Pharmaceutical Engineering (RCPE) GmbH, 8010 Graz, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Fathollahi
authors.affiliation: Rutgers University, Department of Chemical & Biochemical Engineering, NJ, USA.
authors.forename: R
authors.initials: R
authors.lastname: Ramachandran
authors.affiliation: Research Center Pharmaceutical Engineering (RCPE) GmbH, 8010 Graz, Austria; Graz University of Technology, Institute of Process and Particle Engineering, 8010 Graz, Austria. Electronic address: khinast@tugraz.at.
authors.forename: J G
authors.initials: JG
authors.lastname: Khinast
mesh_terms: D004867:Equipment Design / Q000295:instrumentation / Q000379:methods; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D011208:Powders / Q000008:administration & dosage*; D013557:Switzerland; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations; D011208:Powders
keywords: Compartment model; Continuous blending; DEM; Feed rate robustness; Micro feeding; Powder feeding; Vibratory sieve