Nanoparticles with reduced crystallinity are normally produced by bottom-up (precipitation) processes: however, the drug loading can be limited. The objective was to generate such nanoparticles using modified drugs coupled with high pressure homogenization (HPH) and investigate the coeffects of particle size and solid state on dissolution. Indomethacin and quercetin were selected. Indomethacin was quench-cooled and showed a reduction in crystallinity. Freeze-dried indomethacin exhibited polymorphism transformation. Quercetin was processed by using rotary-evaporation with povidone to achieve amorphous solid dispersion. All modified drugs were nanosized to produce nanosuspensions. Modified indomethacin improved HPH efficiency; however, the quercetin rotary-evaporation sample did not contribute, with the alteration of the microstructure being the main reason. Dissolution experiments confirmed that compared to the solid state, the particle size (200-500 nm) contributed to the dissolution of indomethacin. For quercetin, the obtained nanosuspension was amorphous after homogenization and showed optimized dissolution, indicating the importance of both size and crystallinity. (C) 2020 Elsevier B.V. All rights reserved.