title: An investigation into the rheology of pharmaceutical inter-granular material bridges at high shear rates.
abstract: OBJECTIVE
  This study was undertaken to investigate the rheological properties of inter-granular material bridges on the nano-scale when strained at high shear rates.
  
  
  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 As the probe was withdrawn from the granule surface tan delta initially increased rapidly from zero to a plateau phase.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.
authors.affiliation: Laboratory of Biophysics and Surface Analysis, School of Pharmacy, The University of Nottingham, Nottingham, NG7 2RD, UK.
authors.forename: Barry
authors.initials: B
authors.lastname: Crean
authors.forename: Xinyong
authors.initials: X
authors.lastname: Chen
authors.forename: Simon R
authors.initials: SR
authors.lastname: Banks
authors.forename: Walter G
authors.initials: WG
authors.lastname: Cook
authors.forename: Colin D
authors.initials: CD
authors.lastname: Melia
authors.forename: Clive J
authors.initials: CJ
authors.lastname: Roberts
mesh_terms: D000268:Adhesiveness; D004339:Drug Compounding; D004548:Elasticity; D005079:Excipients / Q000737:chemistry*; D007785:Lactose / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D008962:Models, Theoretical; D010316:Particle Size; D011145:Polyvinyls / Q000737:chemistry*; D016062:Porosity; D011759:Pyrrolidines / Q000737:chemistry*; D012212:Rheology; D014783:Viscosity
chemical_list: D005079:Excipients; D011145:Polyvinyls; D011759:Pyrrolidines; C505150:poly(N-vinylpyrrolidine); D007785:Lactose