title: Applying surface energy derived cohesive-adhesive balance model in predicting the mixing, flow and compaction behaviour of interactive mixtures.
abstract: OBJECTIVE
  In this study, we investigated the applicability of cohesive-adhesive balance (CAB) model to predict the interactive mixing behaviour of small excipient particles. Further, we also investigated the application of this CAB model to predict the flow and compactibility of resultant blends.
  
  
  METHODS
  Excipients created by co-spraying polyvinylpyrrolidone (PVP, a model pharmaceutical binder) with various l-leucine concentrations were used for this study. Paracetamol was used as model active pharmaceutical ingredient (API). The surface energy was used to derive the work of cohesion (wco) and work of adhesion (wad) to predict the interactive mixing behaviour of the excipients with paracetamol. The blends were visualised under a scanning electron microscopy microscope to assess the interactive mixing behaviour. In addition, the flow performance and tabletting behaviour of various blends were characterised.
  
  
  RESULTS
  The surface-energy derived work of adhesion (wad) between excipient and paracetamol particles increased, while the corresponding work of cohesion (wco) between excipient particles decreased, with increasing l-leucine concentrations. In blends for which the work of cohesion was higher than the work of adhesion (wco>wad), small excipient particles were apparent as agglomerates. For excipients with 5% and higher l-leucine concentrations, the work of adhesion between excipient and paracetamol particles was higher than or equivalent to the work of cohesion between excipient particles (wad⩾wco) and agglomerates were less apparent. This is an indicator of formation of homogeneous interactive mixtures. At 5% (w/w) excipient proportions, blends for which wad⩾wco demonstrated higher compactibility than other blends. Furthermore, at 10% (w/w) and higher excipient proportions, these blends also demonstrated better flow performance than other blends.
  
  
  CONCLUSIONS
  In conclusion, this is the first study to demonstrate that surface-energy derived CAB data effectively predict the interactive mixing behaviour of small excipient particles. Furthermore, at certain proportions of small excipient particles the CAB model also predicts the flow and compaction behaviour of the API/excipient blends.
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Sharad
authors.initials: S
authors.lastname: Mangal
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Felix
authors.initials: F
authors.lastname: Meiser
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Tan
authors.affiliation: CSIRO Materials Science and Engineering, Bayview Avenue, Clayton, VIC 3168, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gengenbach
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: David A V
authors.initials: DA
authors.lastname: Morton
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia. Electronic address: Ian.Larson@monash.edu.
authors.forename: Ian
authors.initials: I
authors.lastname: Larson
mesh_terms: D002626:Chemistry, Pharmaceutical; D008855:Microscopy, Electron, Scanning; D008962:Models, Theoretical; D013499:Surface Properties
keywords: Cohesion–adhesion balance; Compactibility; Direct compression; Flow; High-dose API; Paracetamol; Polyvinylpyrrolidone; Surface energy; Work of adhesion; Work of cohesion; l-Leucine