We prepared hybrid nanocrystal-amorphous solid dispersions (HyNASDs) to enhance the dissolution of a poorly soluble drug, griseofulvin (GF), and elucidated the roles of a surfactant, sodium dodecyl sulfate (SDS), and two polymers, HPC and Soluplus. Wet-milled suspensions containing 1:1 to 1:5 GF:polymer mass ratios, with and without SDS, were spray-dried. HyNASD formation was confirmed via DSC, XRPD, and Raman spectroscopy. In dissolution tests, due to its sub-ambient glass transition temperature, poor miscibility with GF, its inability to inhibit GF recrystallization, HPC provided HyNASDs with low supersaturation capability (<= 50%) even at the highest loading (1:5) with/without SDS. Contrarily, owing to its stronger intermolecular interactions-miscibility with GF, and its kinetic solubilization-inhibition of GF recrystallization observed in desupersaturation tests, Soluplus, with SDS, in HyNASDs achieved remarkably high supersaturation (>250%). SDS provided enhanced wettability, allowing for fast supersaturation from Soluplus-based HyNASDs (similar to 300% within 20 min), while higher Soluplus loading led to higher supersaturation. (C) 2019 Elsevier B.V. All rights reserved.