1 research outputs found
Multimodal Nonlinear Optical Imaging for Sensitive Detection of Multiple Pharmaceutical Solid-State Forms and Surface Transformations
Two
nonlinear imaging modalities, coherent anti-Stokes Raman scattering
(CARS) and sum-frequency generation (SFG), were successfully combined
for sensitive multimodal imaging of multiple solid-state forms and
their changes on drug tablet surfaces. Two imaging approaches were
used and compared: (i) hyperspectral CARS combined with principal
component analysis (PCA) and SFG imaging and (ii) simultaneous narrowband
CARS and SFG imaging. Three different solid-state forms of indomethacinî—¸the
crystalline gamma and alpha forms, as well as the amorphous formî—¸were
clearly distinguished using both approaches. Simultaneous narrowband
CARS and SFG imaging was faster, but hyperspectral CARS and SFG imaging
has the potential to be applied to a wider variety of more complex
samples. These methodologies were further used to follow crystallization
of indomethacin on tablet surfaces under two storage conditions: 30
°C/23% RH and 30 °C/75% RH. Imaging with (sub)Âmicron resolution
showed that the approach allowed detection of very early stage surface
crystallization. The surfaces progressively crystallized to predominantly
(but not exclusively) the gamma form at lower humidity and the alpha
form at higher humidity. Overall, this study suggests that multimodal
nonlinear imaging is a highly sensitive, solid-state (and chemically)
specific, rapid, and versatile imaging technique for understanding
and hence controlling (surface) solid-state forms and their complex
changes in pharmaceuticals