Microstructure-centric ultrasonic evaluation of granular composite oral solid dosage tablets

The medium of a compressed pharmaceutical Oral Solid Dosage (OSD) form is a granular microcomposite with complex bonding and structure at both macro- and micro-scale levels, in mechanical equilibrium with residual stresses. The reproducible microstructure of an OSD product underlies its Critical Quality Attributes (CQAs) and serves as a cumulative indicator of both the quality of the starting materials and the effectiveness of the unit operations used in its manufacture. A quantitative understanding of the compact microstructure and its microviscoelasticity is essential for controlling drug-release performance. High-frequency, short-wavelength ultrasonic elastic pulses enable micro-viscoelastic granular characterization because their measurable dispersion and attenuation respond directly to both granular boundary scattering and intrinsic viscoelastic losses at the micro-scale, providing a non-destructive, volumetric probe of internal contact networks, porosity, granular bonding, and relaxation behavior. Models of elastic-wave propagation in viscoelastic granular media remain poorly understood, especially for the simultaneous prediction of microstructural parameters and microviscoelastic constants. Such a characterization challenge arises because these effects are difficult to distinguish, as they similarly affect ultrasonic wave attenuation and dispersion. The current study introduces a deterministic framework and experimental data in OSD compacts with narrow grain-size distributions. This ultrasonic characterization framework couples Zener micro-viscoelasticity with Rayleigh scattering to model granularity, enabling analysis of frequency-dependent longitudinal-wave attenuation and dispersion during ultrasonic propagation through OSD compacts. Collectively, the reported results demonstrate a novel, cost-effective, computationally efficient, and scalable ultrasonic methodology that supports rapid Real-Time Release Testing of microstructural and viscoelastic properties of OSD forms.