title: Structural elucidation of rapid solution-mediated phase transitions in pharmaceutical solids using in situ synchrotron SAXS/WAXS.
abstract: In situ elucidation of kinetics of solution-mediated phase transformations using direct structural determination has been achieved using synchrotron SAXS/WAXS radiation. Using theophylline as a model drug with known phase transformation from anhydrate to monohydrate form in aqueous conditions within a few minutes, the kinetics of the structural transition were resolved at the second scale, and the results achieved agreed well with those determined using indirect approaches such as Raman spectroscopy. The recrystallization of the monohydrate in situ (due to its lower solubility) from dissolved anhydrate solution (higher solubility) is demonstrated directly, highlighting a major issue for such compounds in application. The technique has the additional benefit of having the potential to identify intermediate structures which are not readily achievable with in situ spectroscopic techniques, as well as being amenable to high throughput approaches.
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Johan
authors.initials: J
authors.lastname: Boetker
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
authors.forename: Jukka
authors.initials: J
authors.lastname: Rantanen
authors.forename: Adrian
authors.initials: A
authors.lastname: Hawley
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Boyd
mesh_terms: D007700:Kinetics; D044367:Phase Transition; D012995:Solubility; D012996:Solutions / Q000737:chemistry*; D013059:Spectrum Analysis, Raman / Q000379:methods; D017356:Synchrotrons; D013678:Technology, Pharmaceutical / Q000379:methods*; D013806:Theophylline / Q000737:chemistry; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D012996:Solutions; D014867:Water; D013806:Theophylline