  We demonstrate instrumentation and methods to enable fluorescence-detected
photothermal infrared (F-PTIR) microscopy, then demonstrate the utility of
F-PTIR to characterize the composition within phase-separated domains of model
amorphous solid dispersions (ASDs) induced by water sorption. In F-PTIR,
temperature-dependent changes in fluorescence quantum efficiency are shown to
sensitively report on highly localized absorption of mid-infrared radiation.
The spatial resolution with which infrared spectroscopy can be performed is
dictated by fluorescence microscopy, rather than the infrared wavelength.
Following proof of concept F-PTIR demonstration on model systems of
polyethylene glycol (PEG) and silica gel, F-PTIR enabled the characterization
of chemical composition within inhomogeneous ritonavir /
polyvinylpyrrolidone-vinyl acetate (PVPVA) amorphous dispersions. Phase
separation is implicated in the observation of critical behaviors in ASD
dissolution kinetics, with the results of F-PTIR supporting the formation of
phase-separated drug-rich domains upon water absorption in spin-cast films.
