Efficient handling and transport of fine-particle powders can be difficult because of the highly cohesive nature of the bulk
powder mass. It is well reported in the literature that the application of nanosized guest dry powder coatings, such as silicon
dioxide, onto the surfaces of these cohesive host particles can effectively reduce the attractive forces between them (1–5).
The fine nanoparticles increase the spacing between the host particles and increase the apparent surface roughness, which
decreases the host particle cohesive van der Waals attractions (5, 6). After dry powder coating, the bulk powder exhibits
increased bulk density, improved powder flow performance, and easy fluidization behavior, all of which can significantly improve
manufacturing performance (1–5). This result is of significant benefit to pharmaceutical powder processing because the easy
transport of large bulk quantities of powder through unit operations is necessary to manufacture solid dosage forms such as
capsules and tablets.
It was recently demonstrated that conventional pharmaceutical processing equipment, namely a comil, can effectively apply
dry powder coatings of silicon dioxide onto active pharmaceutical ingredients (APIs) and excipients without causing attrition
of the host's primary particles (1). This discovery is important because comils can be operated in a continuous manufacturing
process and are commonly available at pharmaceutical product manufacturing sites. Although the comil is a simple, effective,
and scalable unit operation for applying dry powder coatings, the systematic study of the process operational design space,
such as screen size and impeller speed, may be required to optimize the coating performance. This iterative method may not
be possible in early drug product development because of the limited available quantities of API (often less than 50 g) and
the potential for improved performance after dry powder coating may be overlooked, especially as API synthesis, isolation,
and sizing processes change often. Therefore, alternative (or complementary) methods for applying dry powder coatings would
be desirable during early product development.
A laboratory scale resonant acoustic mixer (LabRAM) similar to the one shown in Figure 1 was evaluated as a potential tool
for dry powder coating (7, 8). The LabRAM is a sophisticated bench-top mixer that exploits low frequency, high intensity,
acoustic energy to rapidly fluidize and disperse as much as 500 g of a variety of materials. The RAM uses acoustic energy
to mix the desired media through an oscillating mechanical driver that accelerates the mixing vessel by as much as 100 times
the acceleration of gravity. The propagation of mechanical energy through a system of plates, weights, and springs creates
an acoustic pressure wave in the mixing vessel. The frequency of the driver is optimized by the control system so that the
system operates at resonance. By operating at resonance, the acoustic energy is absorbed by the media. The efficient mixing
is accomplished by creating a homogenous shear zone throughout the mixing vessel without imparting excess energy and without
the aid of mixing media or impellers. This approach seems promising because the RAM can mix at high acceleration and amplitude
and therefore induce significant shear strain within the bulk powder in a short time. Related work by Davé and coworkers has
demonstrated that when high degrees of shear are induced (e.g., by impact coaters) to disperse fine particles, the particles
preferentially adhere to the surface of larger host particles after processing (2, 3, 5).
Figure 1: Laboratory-scale resonant acoustic mixer (LabRAM), including the vacuum–deaeration unit (left), mixing unit (center),
and control unit (right). (FIGURE 1 IS COURTESY OF RESODYN CORPORATION)
In this study, the RAM was evaluated as a tool for applying various dry powder coatings, such as silicon dioxide, to pharmaceutical
excipients and APIs. The effect of these coatings on powder bulk density, particle size, and shear cell flow performance were
used as indicators of performance enhancement, and the results were compared to those of dry powder coating using a comil.