High-intensity ultrasound (HIU) is increasingly utilized for particle size reduction in pharmaceutical suspensions, offering a top-down, energy-efficient alternative to traditional milling methods. In this study, we investigate the deagglomeration behavior of highly concentrated ibuprofen slurries under HIU using batch-type and flow-through sonication systems. Scanning electron microscopy (SEM), dynamic light scattering (DLS), and rheological measurements were employed to characterize particle morphology, size distribution, and flow properties before and after sonication.
Our results demonstrate that dispersion concentration is a dominant factor influencing size reduction efficacy, surpassing processing time at fixed power inputs. As observed, reduced interparticle spacing at higher solid loadings reduced ultrasound penetration depth and cavitation efficiency. This attenuation-limited regime is described by a simple mechanistic model that incorporates cavitation zone density, energy dissipation, and interparticle spacing as functions of dispersion concentration.
To support this framework, we developed both analytical and numerical models of ultrasonic energy distribution and velocity fields within the reactor. Finite element simulations were conducted to resolve localized cavitation-induced velocity gradients and energy intensities as functions of spatial location and slurry viscosity. These simulations revealed heterogeneous energy distribution patterns and identified stagnation zones correlated with inefficient deagglomeration.
These findings provide a new framework for optimizing ultrasonic processing conditions in concentrated pharmaceutical systems, highlighting the importance of concentration-dependent cavitation attenuation and reactor hydrodynamics in process design. Our work supports broader efforts in continuous, modular pharmaceutical manufacturing platforms and offers a scalable route to achieve targeted particle size distributions in poorly soluble drugs.
