title: Amorphism and Thermal Decomposition of Salicylsalicylic Acid-A Cautionary Tale.
abstract: Salicylsalicylic acid ("Salsalate") is a non-steroidal anti-inflammatory drug with anti-rheumatic properties, whose amorphous form offers the potential for enhanced dissolution rates and improved bioavailability compared with its crystalline counterpart. It has been reported to form a stable glassy phase on heating and rapid quenching. A number of the existing studies of the solid-state structure of salsalate and of its thermal decomposition contain information that is difficult to reconcile. In this article, we review much of the existing literature in light of our own recent studies using solution-state nuclear magnetic resonance, mass spectrometry, and solid-state infrared spectroscopy, and conclude that much of the literature data relating to melting and the glassy state is questionable due to failure to take into account the effects of thermal decomposition.
authors.affiliation: Department of Chemistry, University of Durham, Durham, UK.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Aguilar
authors.affiliation: Department of Chemistry, University of Durham, Durham, UK.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Ball
authors.affiliation: Department of Chemistry, University of Durham, Durham, UK.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Coxon
authors.affiliation: Department of Chemistry, University of Durham, Durham, UK. Electronic address: a.m.kenwright@durham.ac.uk.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Kenwright
authors.affiliation: Department of Chemistry, University College London, London, UK.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Lancaster
authors.affiliation: Department of Chemistry, University of Durham, Durham, UK.
authors.forename: Jackie A
authors.initials: JA
authors.lastname: Mosely
authors.affiliation: Department of Chemistry, University of Durham, Durham, UK.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Mutton
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000032:analysis* / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D012459:Salicylates / Q000032:analysis* / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D012459:Salicylates; C014182:salicylsalicylic acid
keywords: FTIR; NMR spectroscopy; amorphous; analysis; liquid chromatography; mass spectrometry