The current study sought to design a quickly dissolving, high drug loading nanocrystal-based solid dispersion (NC-SD) in order to improve the dissolution of poorly soluble drugs.The NC-SD was prepared by means of combination of homogenization and spray-drying. Polymer hydroxypropylmethylcellulose (HPMC) was used as baseline dispersant for NC-SD of the model drug - andrographolide (AG). Three superdisintegrants cohomogenized with HPMC were used as codispersant for AG-NC-SD and compared to common water-soluble dispersants - mannitol and lactose. The dissolution characterization and oral bioavailability of AG-NC-SD were evaluated.The AG-NC-SD with the higher concentration of HPMC exhibited fast dissolution due to the enhanced wettability of HPMC. The water-soluble codispersants (mannitol and lactose) did not completely prevent AG-NC from aggregation during spray-drying. To achieve much faster AG release, cohomogenized superdisintegrants at a level of 20% must be used along with 25% HPMC. Compared with water-soluble dispersants like mannitol and lactose, superdisintegrants with high swelling capacity were much more effective dispersants for enhancing fast redispersion/dissolution of AG-NC-SD via a swelling-triggered erosion/disintegration mechanism. Surfactant-free AG-NC-SD with 15% cohomogenized sodium carboxymethyl starch combined with 15% HPMC and 10% lactose enhanced the dissolution further, without comprising drug loading, exhibited a barely compromised dissolution rate compared to precursor NC suspensions (>50), and possessed drug loading up to 67.83%±1.26%. The pharmacokinetics results also demonstrated that the AG-NC-SD significantly improved the bioavailability in vivo of AG (<0.05), compared with to the coarse AG.This study illustrates that a quickly dissolving, high drug load, surfactant-free NC-SD can be prepared by using a superdisintegrant as codispersant, and provides a feasible strategy to improve the oral bioavailability of poorly soluble drugs.