Materials and methods
A selection of pharmaceutical powders were chosen as host particles with different particle sizes, particle shapes, and chemistry:
ibuprofen (50 grade and 90 grade, BASF), acetaminophen (micronized, Mallinckrodt Baker), proprietary active pharmaceutical
ingredients (API "A" and API "B," Pfizer), mannitol (powder grade, SPI Pharma), and lactose monohydrate (310 grade, Foremost
Farms). Four guest particles were selected and represented a range of small microsized or nanosized particles commonly used
as glidants or lubricants in solid dosage formulations: hydrophobic silicon dioxide (Aerosil R972, Evonik/Degussa), hydrophilic
silicon dioxide (Aerosil 200, Evonik/Degussa), titanium dioxide (USP grade, Brenntag Specialties), and magnesium stearate
(HyQual, Mallinckrodt Baker).
RAM dry powder coating.
A resonant acoustic mixer (LabRAM, 500 g capacity, Resodyn) was used to prepare the coated particles in small batches (~20
g). The host and guest particles were placed into amber glass bottles and mixed for as much as 10 min at a frequency of 60–61
Hz and a mechanical driver magnitude of 75–80 times the acceleration of gravity. The mixing oscillation mixing frequency was
optimized by the RAM driver control module to mix the powder at resonance.
Comil dry powder coating.
An overdriven comil (model 197, Quadro Engineering) was also used to prepare dry-coated particles. Details of this approach
for coating were previously reported (1). This process required the selection of comil operating conditions (i.e., screens,
impeller, operating speed, and the powder feeding rate) to maximize dispersion of the guest particles and enable throughput
without screen blinding. A round-edged impeller rotating at a tip speed of 2.4 m/s and round hole screens (0.457 to 0.813
mm opening) were selected to maximize residence time and minimize host-particle attrition. The screen opening size was slightly
above the maximum particle size of the host particle and the powder was manually charged to the mill at 10–200 g/min.
Powder characterization.
Photomicrographs were taken with a scanning electron microscope (FEI Quanta 200, FEI) using a working distance of 10 mm with
an accelerating voltage of 5 kV. The particle-size distribution was determined using a laser-diffraction particle-size analyzer
(Sympatec HELOS/RODOS, Sympatec) with dry dispersion capability. The bulk density was determined using the USP <616> method. The flow behavior of powders equilibrated at 50% relative humidity was determined using an annular shear cell
(Schulze Ring Shear Tester model RST-XS, Wolfenbüttel, Germany) using a preconsolidation stress of 4 kPa. The ratio of the
principal consolidation stress to the unconfined yield strength was used to calculate the flow function coefficient (FFC).
The FFC was used as an indicator of powder flow performance. Powders with FFC values between 4 and 10 were considered easy
flowing, and higher FFC values indicate superior flow behavior (9).
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