Performance Evaluation of a High-Precision Low-Dose Powder Feeder

Abstract

Highly potent active pharmaceutical ingredients (APIs) and low-dose excipients, or excipients with very low density, are notoriously hard to feed with currently available commercial technology. The micro-feeder system presented in this work is capable of feeding low-dose rates of powders with different particle sizes and flow properties. Two different grades of lactose, di-calcium phosphate, croscarmellose sodium, silicon dioxide, a spray-dried intermediate, and an active ingredient were studied to vary material properties to test performance of the system. The current micro-feeder system is a volumetric feeder combined with a weighing balance at the outlet that measures feeder output rates. Feeding results are shown as a so-called “displacement-feed factor” curve for each material. Since the powder mass and volume are known in the micro-feeder system, in this work, we characterized an observed density variation during processing via a “displacement-feed factor” profile for each of the fed powders. This curve can be later used for calibrating the system to ensure an accurate, constant feed rate and in addition predicting feeding performance for that material at any feed rate. There is a relation between powder properties and feeding performance. Powders with finer particles and higher compressibility show densification during their feeding process. However, powders with larger particles and lower compressibility show both “densification” and “powder bed expansion,” which is the manifestation of dilation and elastic recovery of particles during the micro-feeding process. Through the application of the displacement-feed factor, it is possible to provide precise feeding accuracy of low-dose materials. Graphical abstract

Development of a Controlled Continuous Low-Dose Feeding Process

“…The micro-feeder system, described by Fathollahi et al (30), was augmented to include a LIW option. The microfeeder consists of a cartridge, which contains the powder, a moveable piston actuated via a syringe pump to displace the powder, and a scraper to transport the material to the process.…”

“…During this step, the powder in the cartridge is tapped and compacted to the powder tapped-density state. Details of the preconditioning procedure are provided in our previous work (30).…”

“…A benefit of the micro-feeder system is that the system is robust and stable, and feeding is reproducible. Specifically, the displacement feed factor is reproducible yet unique (30) for each material and depends on the powder properties, such as the particle size, elastic behaviour, and bulk and tapped densities. Most importantly, the displacement feed factor is not affected by the feed rate (30) for the tested materials in the investigated ranges.…”

“…The high-order polynomial was chosen in order to capture the more complex shape of the displacement feed factor curve of di-calcium phosphate (30).…”

“…Low-dose feeding of cohesive materials, such as highly potent APIs (HPAPIs) and lubricants (8), is a challenge due to the inherent feeder variability (11). In our previous study (30), a novel micro-feeder system was introduced, which enables the feeding of powders with diverse powder properties (e.g., size, density, flow properties, and cohesivity) at feed rates as low as 1 g/h. In addition, one API and one spraydried intermediate (SDI), both highly cohesive, were fed to highlight the industrial applicability of the micro-feeder system.…”