title: The role of physico-chemical and bulk characteristics of co-spray dried L-leucine and polyvinylpyrrolidone on glidant and binder properties in interactive mixtures.
abstract: In this study, polyvinylpyrrolidone (PVP) was spray dried with l-leucine (PVP-Leu) to create a prototype multifunctional interactive excipient. The physico-chemical and bulk properties such as particle size, surface composition, surface energy and bulk cohesion of PVP-Leu was measured and compared against pure spray dried PVP (PVP-SD). The mixing behaviour of these excipients and their effect on flow and binder activity of paracetamol was assessed. The mean particle sizes of PVP-Leu PVP-SD and PVP were 2.5, 2.1 and 21.9μm, respectively. Surface composition characterization indicated that l-leucine achieved higher concentrations on the surface compared to the bulk of the PVP-Leu particles. The surface energy of PVP-Leu was significantly lower compared to PVP-SD. In addition, PVP-Leu exhibited a significantly lower bulk cohesion compared PVP-SD. The excipients were blended with paracetamol and qualitative characterization indicated that PVP-Leu blended more homogeneously with paracetamol compared to PVP-SD. Both PVP-Leu and PVP-SD then exhibited a significantly improved binder activity compared to PVP. The flow of the paracetamol was markedly improved with PVP-Leu while PVP-SD and PVP had negligible effect on its flow. This study reveals how physico-chemical and bulk properties of such prototype interactive excipients can play a key role in determining multi-factorial excipient performance.
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Science, 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 Science, 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 Science, 381 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Satu
authors.initials: S
authors.lastname: Lakio
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Science, 381 Royal Parade, Parkville, VIC 3052, Australia. Electronic address: david.morton@monash.edu.
authors.forename: David
authors.initials: D
authors.lastname: Morton
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Science, 381 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 / Q000008:administration & dosage* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry*; D007930:Leucine / Q000737:chemistry*; D010316:Particle Size; D011205:Povidone / Q000737:chemistry*
chemical_list: D005079:Excipients; D000082:Acetaminophen; D011205:Povidone; D007930:Leucine
keywords: Co-processed; Interactive excipient; Lubricant; Polyvinylpyrrolidone