Roles of surfactant and polymer in drug release from spray-dried hybrid nanocrystal-amorphous solid dispersions (HyNASDs)

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 (~300% within 20 min), while higher Soluplus loading led to higher supersaturation.