title: Relationship between the cohesion of guest particles on the flow behaviour of interactive mixtures.
abstract: In this study, we aimed to investigate the effects cohesion of small surface-engineered guest binder particles on the flow behaviour of interactive mixtures. Polyvinylpyrrolidone (PVP) - a model pharmaceutical binder - was spray-dried with varying l-leucine feed concentrations to create small surface-engineered binder particles with varying cohesion. These spray-dried formulations were characterised by their particle size distribution, morphology and cohesion. Interactive mixtures were produced by blending these spray-dried formulations with paracetamol. The resultant blends were visualised under scanning electron microscope to confirm formation of interactive mixtures. Surface coverage of paracetamol by guest particles as well as the flow behaviour of these mixtures were examined. The flow performance of interactive mixtures was evaluated using measurements of conditioned bulk density, basic flowability energy, aeration energy and compressibility. With higher feed l-leucine concentrations, the surface roughness of small binder particles increased, while their cohesion decreased. Visual inspection of the SEM images of the blends indicated that the guest particles adhered to the surface of paracetamol resulting in effective formation of interactive mixtures. These images also showed that the low-cohesion guest particles were better de-agglomerated that consequently formed a more homogeneous interactive mixture with paracetamol compared with high-cohesion formulations. The flow performance of interactive mixtures changed as a function of the cohesion of the guest particles. Interactive mixtures with low-cohesion guest binder particles showed notably improved bulk flow performance compared with those containing high-cohesion guest binder particles. Thus, our study suggests that the cohesion of guest particles dictates the flow performance of interactive mixtures.
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash University, Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Sharad
authors.initials: S
authors.lastname: Mangal
authors.affiliation: CSIRO Materials Science and Engineering, Bayview Avenue, Clayton, VIC 3168, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gengenbach
authors.affiliation: Freeman Technology, Miller Court, Tewkesbury Business Park, Severn Dr, Tewkesbury, Gloucestershire GL20 8DN, United Kingdom.
authors.forename: Doug
authors.initials: D
authors.lastname: Millington-Smith
authors.affiliation: Freeman Technology, Miller Court, Tewkesbury Business Park, Severn Dr, Tewkesbury, Gloucestershire GL20 8DN, United Kingdom.
authors.forename: Brian
authors.initials: B
authors.lastname: Armstrong
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash University, Royal Parade, Parkville, VIC 3052, Australia. Electronic address: david.morton@monash.edu.
authors.forename: David A V
authors.initials: DA
authors.lastname: Morton
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash University, Royal Parade, Parkville, VIC 3052, Australia. Electronic address: Ian.Larson@monash.edu.
authors.forename: Ian
authors.initials: I
authors.lastname: Larson
mesh_terms: D000082:Acetaminophen / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D005079:Excipients / Q000737:chemistry; D007930:Leucine / Q000737:chemistry; D010316:Particle Size; D011205:Povidone / Q000737:chemistry; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D005079:Excipients; D000082:Acetaminophen; D011205:Povidone; D007930:Leucine
keywords: Bulk density; FT4; Interactive mixture; Paracetamol; Particle engineering; Polyvinylpyrrolidone; Shear cell; Surface coverage; X-ray photoelectron spectroscopy; l-Leucine