Structural elucidationof rapid solution-mediatedPhase transitions in pharmaceutical solids using in situ synchrotron SAXS/WAXS

TY - JOUR

T1 - Structural elucidationof rapid solution-mediatedPhase transitions in pharmaceutical solids using in situ synchrotron SAXS/WAXS

AU - Bøtker, Johan Peter

AU - Rades, Thomas

AU - Rantanen, Jukka

AU - Hawley, Adrian

AU - Boyd, Ben J.

PY - 2012/9/4

Y1 - 2012/9/4

N2 - 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.

AB - 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.

KW - engineering

U2 - 10.1021/mp3003072

DO - 10.1021/mp3003072

M3 - Journal article

C2 - 22871088

SN - 1543-8384

VL - 9

SP - 2787

EP - 2791

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

IS - 9

ER -