While these studies demonstrate that substan al insights into the phase behavior of ASDs can be gained from the use of fluorescent marker molecules, and the instrumenta on is highly accessible, direct in situ chemically-and solid-state specific op cal imaging of the API(s) and excipients themselves, at equally good spa al resolu on, would have benefits. Firstly, it would allow the sample to be analyzed as is and without any manipula on as such, and naturally avoids having to rely on the assump on that the marker molecules associate with the target molecules as predicted. Secondly, the distribu on of numerous components in the system, including water, could poten ally be (semi-)quan ta vely imaged. Finally, a suitable direct imaging technique could also provide solid-state specificity. A enuated total reflec on Fourier transform infrared (ATR-FTIR) macroscopic imaging has been developed by the research group of Kazarian in par cular, to quan vely image ASD interac ons with dissolu on media, including water ingress, drug and polymer dissolu on, and drug crystalliza on in ASDs. They have also coupled the technique with magne c resonance imaging (MRI) and Raman microscopy (over a much smaller region), to further image water ingress in 3D and drug crystalliza on, respec vely 5 . While the ATR-FTIR imaging has provided tremendous insights into ASD behavior in dissolu on media , the lateral spa al resolu on is at least several micrometers (in contrast to sub-micron lateral spa al resolu on for fluorescence imaging). Furthermore, since the sampling is immediately adjacent to the ASD-ATR crystal interface (within approximately 1 µm), the poten al influence of the ATR crystal itself on the ASD behavior, that is not representa ve of the ASD more generally, needs to be kept in mind. Confocal Raman microscopy has the poten al to fulfill the above criteria, and, depending on the setup, can offer a spa al resolu on comparable to confocal fluorescence microscopy. Recently Krummnow et al. employed Raman line mapping to quan ta vely image waterinduced phase separa on in amorphous solid dispersions during storage at different humidi es, again using ritonavir and PVPVA ASDs as model systems . Almost a decade earlier, Tres and coworkers 4 imaged drug loading dependent crystalliza on of felodipine in PVPVA ASDs in aqueous media with in situ confocal Raman microscopy. Both these studies involved analysis of the ASDs over a me scale of many hours, which allows the sufficient collec on of the inherently weak spontaneous Raman sca ering signal. These mapping mes are too slow to capture fast-paced changes, within seconds or minutes, that can occur in aqueous media.