Micro-viscoelastic Characterization of Compressed Oral Solid Dosage Forms with Ultrasonic Wave Dispersion Analysis

Due to their constituent powders, the materials of advanced compressed oral solid dosage (OSD) forms are micro-composites and strongly visco-elastic at macro- and micro-length scales. The disintegration, drug release, and mechanical strength of OSD forms depend on its micro-texture (such as porosity) and micro-scale physical/mechanical properties. In the current work, an algorithmic ultrasonic characterization framework for extracting the micro-visco-elastic properties of OSD materials is presented, and its applicability is demonstrated with a model material. The proposed approach is based on the effect of visco-elasticity and granularity on the frequency-dependent attenuation of an ultrasonic wave pulse in a composite (granular) and viscous medium. In modeling the material, a two-parameter Zener model for visco-elasticity and a scattering attenuation mechanism based on Rayleigh scattering for long-wave approximation are employed. A novel linear technique for de-coupling the effects of micro-visco-elasticity and scattering on attenuation and dispersion is developed and demonstrated. The apparent Young's modulus, stress, and strain relaxation time constants of the medium at micro-scale are extracted and reported. Based on this modeling and analysis framework, a set of computational algorithms has been developed and demonstrated with experimental data, and its practical utility in pharmaceutical manufacturing and real-time release testing of tablets is discussed.