We studied optimized conditions for preparing ternary hot extrudates (HEs) of glibenclamide (GLB)/polyvinylpyrrolidone (PVP)/sodium dodecyl sulfate to generate stable nanocrystal suspensions following aqueous dispersion. Raman and solid-state NMR measurements of ternary HEs prepared by altering HE conditions revealed that GLB crystallinity in HEs reduced with increased extrusion temperature and count and decreased screw speed. Aqueous dispersions of all HEs temporarily formed GLB nanoparticles with a diameter of 75-420 nm. The suspension from the HEs with the low GLB crystallinity (<22%) precipitated after 4-h storage, while the HEs with the high GLB crystallinity (>22%) formed stable nanocrystal suspension. Interestingly, the number of GLB nanoparticles <150  nm was different despite aqueous dispersion of HEs with similar GLB crystallinity, reflecting the different GLB crystalline size in those HEs. Although both the crushing by shear force and GLB dissolution into PVP reduced GLB crystalline size, the crushing GLB crystal by the shear force has a relatively high ability to decrease GLB crystalline size without excess amorphization of GLB. Performing the hot extrusion at a low temperature, a high screw speed, and maximizing extrusion count with GLB crystallinity >22% led to formation of small and stable nanocrystal suspensions.