title: Determination of physical and chemical stability in pressurised metered dose inhalers: potential new techniques.
abstract: BACKGROUND
  Pressurised metered dose inhalers (pMDIs) are subject to rigorous physical and chemical stability tests during formulation. Due to the time and cost associated with product development studies, there is a need for online techniques to fast screen new formulations in terms of physical and chemical (physico-chemical) stability. The problem with achieving this is that pMDIs are by their definition, pressurised, making the direct observation of physico-chemical properties in situ difficult.
  
  
  METHODS
  This review highlights the characterisation tools that can enhance the product development process for pMDIs. Techniques investigated include: laser diffraction, Raman spectroscopy, isothermal ampoule calorimetry, titration calorimetry and gas perfusion calorimetry. The operational principles behind each technique are discussed and complemented with examples from the literature.
  
  
  CONCLUSIONS
  Laser diffraction is well placed to analyse real-time physical stability as a function of particle size; however, its use is restricted to suspension pMDIs. Raman spectroscopy can be potentially used to attain both suspension and solution pMDI spectra in real time; however, the majority of experiments are ex-valve chemical composition mapping. Calorimetry is an effective technique in capturing both chemical and physical degradations of APIs in real time but requires redevelopment to withstand pressure for the purposes of pMDI screening.
authors.affiliation: a 1 University of Sydney, The Woolcock Institute of Medical Research, Australia and School of Medicine, Respiratory Technology, Discipline of Pharmacology , Sydney, Australia +61 2 9114 0350 ; Paul.young@sydney.edu.au.
authors.forename: Jesslynn
authors.initials: J
authors.lastname: Ooi
authors.affiliation: a 1 University of Sydney, The Woolcock Institute of Medical Research, Australia and School of Medicine, Respiratory Technology, Discipline of Pharmacology , Sydney, Australia +61 2 9114 0350 ; Paul.young@sydney.edu.au.
authors.forename: Daniela
authors.initials: D
authors.lastname: Traini
authors.affiliation: b 2 Monash University, Monash Institute of Pharmaceutical Sciences , 381 Royal Parade, Parkville, Victoria 3052, Australia.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Boyd
authors.affiliation: c 3 University College London, School of Pharmacy , 29-39 Brunswick Square, London, WC1N 1AX, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Gaisford
authors.affiliation: a 1 University of Sydney, The Woolcock Institute of Medical Research, Australia and School of Medicine, Respiratory Technology, Discipline of Pharmacology , Sydney, Australia +61 2 9114 0350 ; Paul.young@sydney.edu.au.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Young
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D006801:Humans; D036501:Metered Dose Inhalers; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D013059:Spectrum Analysis, Raman; D013535:Suspensions
chemical_list: D004364:Pharmaceutical Preparations; D013535:Suspensions
keywords: Raman; drug stability; fast screening techniques; isothermal calorimetry; laser diffraction; pressurised metered dose inhalers