Investigating key properties of model excipients and binary powder blends using ultrasonic in-die measurements on a compaction simulator
In this work, the recently introduced Kilian Inline Measurement System (KIM) that enables ultrasonic measurements during powder compaction was studied using three pharmaceutical excipients with different properties and particle sizes, applying various amounts of lubricant and different compaction pressures. It was shown that the generated results were highly reproducible, not only in series but also on different days including dismantling and reassembling of the components.
Highlights
The ultrasonic velocity increased for all materials over the compaction process, however, the rate of increase differed between substances with varying deformation behavior.
The overall velocity increase was neither influenced by the initial particle size, nor by the amount of lubricant added.
The decompression signals of the excipients showed characteristic progressions and were mostly independent of the applied pressure.
The velocity profiles could be indicative of changes in the pore structure throughout the compression process.
The measured velocity through a binary mixture (50:50 (w/w)) at a certain solid fraction was in between the velocity through its plain components.
The relation between ultrasonic velocity and increasing compact density differed among the investigated materials and was independent of initial particle size and applied maximum pressure. Since the velocity through a porous solid is dependent on pore volume and shape, velocity profiles have the potential to track changes in the microstructures of the materials. Furthermore, ultrasonic velocities through binary mixtures (50:50 (w/w)) at a given solid fraction were between the values of the plain excipients, but more closely resembled one of their components.
This may be indicative of the compaction behavior and performance of the blend. Overall, ultrasonic instrumentation seems to be a robust and promising tool for the characterization of powders and blends in compaction processes. However, its practical value must still be investigated further including multi-component blends, underlying densification mechanisms, and decompression.
Article information: Melinda Kern, Thomas Riedel, Jörg Breitkreutz, Investigating key properties of model excipients and binary powder blends using ultrasonic in-die measurements on a compaction simulator, International Journal of Pharmaceutics, Volume 613, 2022. https://doi.org/10.1016/j.ijpharm.2021.121381.