title: Relationship between surface concentration of L-leucine and bulk powder properties in spray dried formulations.
abstract: The amino acid L-leucine has been demonstrated to act as a lubricant and improve the dispersibility of otherwise cohesive fine particles. It was hypothesized that optimum surface L-leucine concentration is necessary to achieve optimal surface and bulk powder properties. Polyvinylpyrrolidone was spray dried with different concentration of L-leucine and the change in surface composition of the formulations was determined using X-ray photoelectron spectroscopy (XPS) and time of flight-secondary ion mass spectrometry (ToF-SIMS). The formulations were also subjected to powder X-ray diffraction analysis in order to understand the relationship between surface concentration and solid-state properties of L-leucine. In addition, the morphology, surface energy and bulk cohesion of spray dried formulations were also assessed to understand the relation between surface L-leucine concentration and surface and bulk properties. The surface concentration of L-leucine increased with higher feed concentrations and plateaued at about 10% L-leucine. Higher surface L-leucine concentration also resulted in the formation of larger L-leucine crystals and not much change in crystal size was noted above 10% L-leucine. A change in surface morphology of particles from spherical to increasingly corrugated was also observed with increasing surface l-leucine concentration. Specific collapsed/folded over particles were only seen in formulations with 10% or higher l-leucine feed concentration suggesting a change in particle surface formation process. In addition, bulk cohesion also reduced and approached a minimum with 10% L-leucine concentration. Thus, the surface concentration of L-leucine governs particle formation and optimum surface L-leucine concentration results in optimum surface and bulk powder properties.
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: Ian Wark Research Institute, University of South Australia, Mawson Lakes, SA 5095, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Denman
authors.affiliation: Melbourne School of Engineering, The University of Melbourne, VIC 3010, Australia.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Rowles
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
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia. Electronic address: david.morton@monash.edu.
authors.forename: David A V
authors.initials: DA
authors.lastname: Morton
mesh_terms: D000336:Aerosols; D002626:Chemistry, Pharmaceutical; D002849:Chromatography, Gas; D003460:Crystallization; D018360:Crystallography, X-Ray; D003890:Desiccation; D007930:Leucine / Q000737:chemistry*; D054327:Lubricants / Q000737:chemistry*; D013058:Mass Spectrometry; D008855:Microscopy, Electron, Scanning; D056951:Photoelectron Spectroscopy; D011205:Povidone / Q000737:chemistry; D033362:Powder Diffraction; D011208:Powders; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D000336:Aerosols; D054327:Lubricants; D011208:Powders; D011205:Povidone; D007930:Leucine
keywords: Inter-particle cohesion; Polyvinylpyrrolidone; Spray drying; Surface mapping; l-Leucine