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Table II: Percent change in bulk density of host powders after dry coating with 1 wt% guest particle in the resonant acoustic
mixer for 5 min.
Assessment of host particles. The RAM extent of coating, as measured by the change in bulk density after 5 min of mixing, was examined using five host
powders and four guest powders. The data show that, overall, the Aerosil R972 guest particles were the most effective in increasing
bulk density of the host powders, followed by Aerosil A200 and magnesium stearate (see Table II). On average, titanium dioxide
was the least effective for increasing bulk density. The superiority of the hydrophobic silicon dioxide over hydrophilic silicon
dioxide for lowering interparticulate cohesion is consistent with reports in the literature (4, 5, 10). Similarly, magnesium
stearate as a dry powder coating was also shown to be effective for increasing bulk density when mixed with sufficient mechanical
shear. In fact, compared with silicon dioxide, magnesium stearate was even more effective for improving the performance of
some powders when dry coated with mechanical shear, and is sensitive to processing speed and processing time (11). These results
suggest that there is no universal optimal guest particle, but rather they must be individually chosen for each host and mixing
system. The RAM mixing approach is well suited for this purpose as material combinations can be quickly assessed with minimal
powder consumption and experimentation time.
Figure 4: Change in powder bulk density and flow performance of uncoated host particles (O), comil dry coated powders (C),
and RAM dry coated powders (R). aerosil R972 is used as the guest particle for the dry-coated powders.
Relationship between comil and RAM dry powder coating. The bulk density and flow performance of uncoated powders were compared with comil dry coated powders and RAM dry coated powders
to assess relative capabilities for dry powder coating. Figure 4 shows that when using 1 wt% Aerosil R972 as the guest powder,
the RAM was able to improve the bulk density and flow performance of the host powder. In addition, the RAM was equally, if
not more effective, than the comil for dry powder coating, presumably because of the significantly higher total shear strain
imparted to the bulk powder system. This trend and hypothesis is similar to the observation that the comil is a more efficient
tool for dry powder coating than a low-shear inversion mixer (1). Surprisingly, the relationship between flow and bulk density
was linear (R2 >0.95) for each host particle system, regardless of the dry powder coating method. This finding further supports the qualitative
observation made in comil dry coating studies in which an increase in bulk density was accompanied by an increase in flow
performance (i.e., FFC) (1). Because the material consumption, material preparation time, and process time for dry powder
coating with the RAM are generally lower than for an equivalent comil experiment, this instrument can be used as a screening
tool during dosage form design to benchmark a host powder's maximum dry powder potential (i.e., to define the dry powder coating
endpoint of FFC versus bulk density relationship). This coating extent could then be used as a product quality attribute to
target during transfer and scale-up to the comil, which is a more traditional pharmaceutical process.
Conclusion
The RAM was effective at applying dry powder coatings. The coated powders exhibited higher bulk density and superior powder
flow performance compared with uncoated powders. This work demonstrated the following four main points:
The RAM can effectively increase the bulk density of powders by applying dry powder coatings of silicon dioxide and magnesium
stearate
A linear relationship exists between bulk density and the FFC for powders dry coated with hydrophobic silicon dioxide
Bulk density measurements can be used as a screening method to determine the potential for flow property enhancements
The RAM could be used as a benchmarking tool for comil dry powder coating process optimization.
