An investigation into the rheology of pharmaceutical inter-granular material bridges at high shear rates

Pharm Res. 2009 May;26(5):1101-11. doi: 10.1007/s11095-009-9828-z. Epub 2009 Feb 3.

Abstract

Purpose: This study was undertaken to investigate the rheological properties of inter-granular material bridges on the nano-scale when strained at high shear rates.

Materials and methods: Atomic force microscopy (AFM) was used as a rheometer to measure the viscoelasticity of inter-granular material bridges for lactose:PVP K29/32 and lactose:PVP K90 granules, produced by wet granulation.

Results: The loss tangent (tan delta) and both the storage (G') and loss shear moduli (G'') of inter-granular material bridges were measured as a function of the probe-sample separation distance, oscillation frequency and relative humidity (RH). As the probe was withdrawn from the granule surface tan delta initially increased rapidly from zero to a plateau phase. G'' became increasingly dominant as the bridge was further extended and eventually exceeded G'. At high RH, capillary forces were foremost at bridge rupture, whereas at low RH elastic forces dominated. The effect of increasing frequency was to increase the effective elasticity of the bridge at high RH.

Conclusions: AFM has been employed as a rheometer to investigate the nano-scale rheology of inter-granular material bridges. This novel method may be used to obtain a fundamental understanding how different binders, granulated with different diluent fillers, behave at high shear rates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesiveness
  • Drug Compounding
  • Elasticity
  • Excipients / chemistry*
  • Lactose / chemistry*
  • Microscopy, Atomic Force*
  • Models, Theoretical
  • Particle Size
  • Polyvinyls / chemistry*
  • Porosity
  • Pyrrolidines / chemistry*
  • Rheology
  • Viscosity

Substances

  • Excipients
  • Polyvinyls
  • Pyrrolidines
  • poly(N-vinylpyrrolidine)
  • Lactose