title: Isothermal calorimetry: a predictive tool to model drug-propellant interactions in pressurized metered dose systems.
abstract: The purpose of this work was to evaluate gas perfusion isothermal calorimetry (ITC) as a method to characterize the physicochemical changes of active pharmaceutical ingredients (APIs) intended to be formulated in pressurized metered dose inhalers (pMDIs) after exposure to a model propellant. Spray dried samples of beclomethasone dipropionate (BDP) and salbutamol sulphate (SS) were exposed to controlled quantities of 2H,3H-decafluoropentane (HPFP) to determine whether ITC could be used as a suitable analytical method for gathering data on the behavioural properties of the powders in real time. The crystallization kinetics of BDP and the physiochemical properties of SS were successfully characterized using ITC and supported by a variety of other analytical techniques. Correlations between real and model propellant systems were also established using hydrofluoroalkane (HFA-227) propellant. In summary, ITC was found to be suitable for gathering data on the crystallization kinetics of BDP and SS. In a wider context, this work will have implications on the use of ITC for stability testing of APIs in HFA-based pMDIs.
authors: Respiratory Technology, Woolcock Institute of Medical Research, 431 Glebe Point Road, Glebe, NSW 2037, Australia; Discipline of Pharmacology, Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia.
authors: Jesslynn
authors: J
authors: Ooi
authors: School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.
authors: Simon
authors: S
authors: Gaisford
authors: Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Vic 3052, Australia.
authors: Ben J
authors: BJ
authors: Boyd
authors: Respiratory Technology, Woolcock Institute of Medical Research, 431 Glebe Point Road, Glebe, NSW 2037, Australia; Discipline of Pharmacology, Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia.
authors: Paul M
authors: PM
authors: Young
authors: Respiratory Technology, Woolcock Institute of Medical Research, 431 Glebe Point Road, Glebe, NSW 2037, Australia; Discipline of Pharmacology, Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address: daniela.traini@sydney.edu.au.
authors: Daniela
authors: D
authors: Traini
mesh_terms: D000335:Aerosol Propellants / Q000737:chemistry*; D000420:Albuterol / Q000008:administration & dosage / Q000737:chemistry; D001507:Beclomethasone / Q000008:administration & dosage / Q000737:chemistry; D002151:Calorimetry / Q000379:methods*; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D005466:Fluorocarbons / Q000737:chemistry*; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D036501:Metered Dose Inhalers; D010420:Pentanes
chemical_list: D000335:Aerosol Propellants; D000420:Albuterol; D001507:Beclomethasone; D005466:Fluorocarbons; D006845:Hydrocarbons, Fluorinated; C008806:perfluoropentane; D010420:Pentanes; C094049:apaflurane
keywords: Aerosol science; Beclomethasone dipropionate; Crystallization; Fluorinated interactions; Isothemal microcalorimetry; Propellant; Salbutamol sulphate; pMDI