(M1130-02-09) Powder Rheology for Batch Comparison During Manufacturing

Purpose: This study details the use of the Micromeritics FT4 Powder Rheometer to determine trackable differences in manufacturing batches where a vendor of an excipient designed to decrease particle cohesion and improve flow in a formulation was changed. This impact was not detected and caused flow filling issues during the vacuum filling process on a Harro Höfliger Modu C MS Drum Filler. Even changes where the excipient content in the formulation was small (4%), the FT4 Powder Rheometer can help determine which blends have the potential to fill correctly and which blends will cause issues.

Methods: Multiple manufacturing batches were sampled and tested on the FT4 Powder Rheometer with a variety of standard and advanced methodologies. Testing included stability and variable flow rate, aeration, compressibility, permeability, and shear rate to determine a variety of powder parameters. Batches of known manufacturability helped determine a baseline of these parameters, and it was determined which parameters were critical. This created at method to predict batches that could be vacuum filled within predetermined process parameter ranges.

Results: Each FT4 testing methodology provided a trackable parameter (or parameters) that could be plotted across batches that could and could not be filled.  The stability and variable flow rate test tracked basic flow energy, flow rate index, specific energy, and conditioned bulk density.  Aeration tracked aeration ratio and aerated energy.  Compressibility measured compressibility.  Permeability measured pressure drop across the powder bed.  The shear rate test measured the cohesion and flow function of the powder.  Across over 20 separate batches, it was shown that although many of the parameters were unable to show differences between batches, conditioned bulk density (Figure 1) and pressure drop (Figure 2) could accurately predict which batches would fail to fill on the Harro Höfliger.  Low conditioned bulk density (≤ 0.22 g/mL) and low pressure (≤ 39.1 mBar) was tracked to batches that were not able to be filled within the validated vacuum range of the Harro Höfliger.

Conclusion: Powder rheology testing on the Micromeritics FT4 Powder Rheometer was sensitive enough to determine parameters on manufacturing batches that were indicative of whether or not those batches could be filled within the validated vacuum range on the Harro Höfliger Modu C MS Drum Filler.


Figure 1: Conditioned Bulk Density


Figure 2: Pressure Drop