Amorphous solid dispersions (ASDs) can potentially increase the apparent solubility and thereby the oral bioavailability of poorly soluble compounds. Furthermore, their physical instability, i.e., potential to crystallize, is a major concern. Our objective was to explore methods for rapid assessment of the physical stability of ASDs. Ketoconazole ASDs were prepared with each of the three polymers, poly(acrylic acid) (PAA), poly(2-hydroxyethyl methacrylate) (PHEMA), and polyvinylpyrrolidone (PVP). The physical stability of these ASDs was evaluated after exposure to 90% RH (25 �C) in an automated water sorption analyzer. The onset time for ketoconazole crystallization, induced by water sorption, was rank ordered as PAA >
PHEMA >
PVP. Additionally, the ability of the polymers to inhibit crystallization on contact with aqueous medium was studied by powder X-ray diffractometry using synchrotron radiation. In this case, the rank ordering was PAA ~ PHEMA >
PVP. To check the validity of our approach, the long-term stability of ketoconazole in ASDs was evaluated in the glassy state, both at 25 and at 40 �C, and was rank ordered as PAA >
PHEMA >
PVP. Crystallization, accelerated by water vapor sorption, can serve as an effective preliminary screening tool to rapidly evaluate and rank order the physical stability of ASDs.