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Figure 2: Scanning electron microscope micrographs of unprocessed (top row), resonant acoustic mixer (RAM) processed without
silicon dioxide (middle row), and RAM processed with aerosil R972 (bottom row) for ibuprofen (left column) and acetaminophen
(right column). The RAM processed ibuprofen without silicon dioxide shows some surface abrasion or melting, and the RAM processed
acetaminophen did not appear to change. (ALL IMAGES AND FIGURES ARE COURTESY OF THE AUTHORS, EXCEPT WHERE OTHERWISE NOTED)
Effect of RAM mixing on powder and particle properties. An examination of the ibuprofen and acetaminophen host particles after mixing showed slight changes to the surfaces of some
of the host particles when processed in the RAM without silicon dioxide. Figure 2 shows what appears to be surface melting
of an ibuprofen particle after mixing without silicon dioxide. Considering the relatively low melting point of ibuprofen (~70
°C), this suggests that interparticle friction may have increased the temperature of the powder during processing significantly
above ambient laboratory temperature (20–25 °C). Some particle–particle abrasion may also have occurred during mixing in the
absence of a glidant. However, the melting and abrasion did not appear in samples that were mixed with silicon dioxide, presumably
because the glidant acted to significantly reduce the friction during mixing. No appreciable changes in particle size, morphology,
or surface texture were observed for the acetaminophen particles. Further investigation is recommended to determine whether
any significant heat was generated during the process, which may cause physical changes to sensitive host particles.
Table I: Particle-size distribution statistics for nprocessed and resonant acoustic mixer dry-powder-coated ibuprofen and
acetaminophen.
The particle-size distributions of the unprocessed ibuprofen and acetaminophen host particles were compared with the silicon
dioxide mixed powders after 10 minutes of processing to determine whether appreciable host particle attrition or agglomeration
had occurred (see Table I). The apparent particle size of the two ibuprofen powders slightly increased after mixing with silicon
dioxide. There was no appreciable change in the particle size of the acetaminophen after mixing with silicon dioxide. It is
hypothesized that the smallest ibuprofen particles adhered to larger particles after mixing. Based on these results, the RAM
did not appear to cause host particle attrition during dry powder coating, but for certain powders, the process could promote
agglomeration or further ordered mixing.
Figure 3: Effect of resonant acoustic mixer mixing time on bulk density of host powders coated with 1% aerosil R972.
The influence of RAM mixing duration was assessed using host particles mixed with 1 wt% Aerosil R972 by periodic sampling.
The extent of mixing was determined indirectly from bulk-density measurements because the silicon dioxide acts as a glidant
to enable host-particle rearrangement when well dispersed over the host particles. In nearly all cases, the powders achieved
a steady-state bulk density after approximately five minutes of mixing (see Figure 3), and therefore a five-minute mixing
time was used in subsequent host-guest particle screening experiments as the standard mixing condition. It is currently hypothesized
that mixing time at resonance can be used to scale up this process.
