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Micro-viscoelastic characterization of compressed oral solid dosage forms with ultrasonic wave dispersion analysis

By Sultan, Tipu; Paul, Shubhajit; Rozin, Enamul Hasan; Tseng, Yin-Chao; Bazzocchi, Michael C. F.; Cetinkaya, Cetin

Published on CMKC

Abstract

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.

Journal

AAPS PharmSciTech. Volume 24, 2022, 22

DOI

10.1208/s12249-022-02483-7

Type of publication

Peer-reviewed journal

Affiliations

  • Clarkson University
  • Boehringer Ingelheim Pharmaceuticals, Inc.

Article Classification

Research Article

Classification Areas

  • Oral Solid Dosage

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