Mechanics of Pharmaceutical Pellets-Constitutive Properties, Deformation, and Breakage Behavior

J Pharm Sci. 2018 Feb;107(2):571-586. doi: 10.1016/j.xphs.2017.08.022. Epub 2017 Sep 18.

Abstract

To ensure robust manufacturing of unit-based oral solid dosage forms with minimal structural imperfections and high mechanical reliability across subsequent processing unit operations (e.g., withstanding mechanical stresses during coating, optional axial compression, handling, packaging, storage, and transport conditions), process design should include consideration of precise limits of accurate micro, macro, and bulk properties of the constituent pellets. This communication presents a comprehensive intricate database of micromechanical properties' and breakage probability distribution functions of pellets, illustrating the stiffening and strengthening effects of coatings and the softening and weakening effects of structural moisture. Further insights such as the (contact) history-dependent softening during decompression, strain hardening on repeated stressing, strength recovery by drying, and the fragmentation pattern by cracking are also presented. The contents herein are based on conveniently performable lab-scale diametrical compression measurements on model microcrystalline cellulose pellets-demonstrating feasibility of the approach and validity of the contribution.

Keywords: compression; excipients; fluid-bed; image analysis; mechanical properties; microcrystalline cellulose; physical characterization; powder technology; solid dosage form; water in solids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cellulose / chemistry*
  • Drug Compounding / methods
  • Drug Implants / chemistry*
  • Excipients / chemistry
  • Reproducibility of Results
  • Stress, Mechanical
  • Tensile Strength

Substances

  • Drug Implants
  • Excipients
  • Cellulose
  • microcrystalline cellulose