LAUSR

&NA; Amorphous solid dispersions (ASDs) are a promising formulation strategy to increase both the apparent aqueous solubility and bioavailability of poorly water‐soluble drugs. Upon dissolution under nonsink conditions, ASDs can generate highly supersaturated drug solutions which can undergo liquid–liquid phase separation (LLPS) and/or crystallization. In this study, the phase behavior of supersaturated solutions generated by antisolvent addition and upon the dissolution of ASDs was evaluated using fluorescence lifetime measurements and several other orthogonal techniques, including steady‐state fluorescence spectroscopy, ultraviolet (UV) extinction and concentration profiles, ultracentrifuge measurements and nanoparticle tracking analysis. Ritonavir and lopinavir were chosen as poorly water‐soluble model drugs, and the polymer, Kollidon VA64, was selected to form the dispersions. The fluorescence lifetime of the environment‐sensitive fluoroprobe, PRODAN, was monitored to determine the occurrence of LLPS and crystallization. It was found that only the 10% w/w drug loading ASDs dissolved to a concentration in solution higher than the LLPS concentration and this led to an increase in the lifetime of PRODAN due to partitioning of the fluoroprobe into the drug‐rich phase. In contrast, the 50% w/w drug loading ASDs did not reach the amorphous solubility, pointing to a dissolution behavior controlled by the low water solubility and high hydrophobicity of the drug. Fluorescence lifetime measurements were demonstrated to be extremely useful for the characterization of the phase behavior of supersaturated solutions of poorly water‐soluble drugs. Graphical abstract Figure. No caption available.