Preparation Nanocrystals of Poorly Soluble Plant Compounds Using an Ultra-Small-Scale Approach

The usage of downscaling technology for producing nanosuspensions/nanocrystals can be beneficial for formulation development, which has attracted increased attention recently. An ultra-small bead milling method (5 mg compound per batch, smallest scale to date) was tested to produce nanocrystals of four poorly soluble plant compounds, i.e., quercetin, rutin, resveratrol, and hesperidin. A particle size of ranged from 200 to 500 nm was obtained for nanosuspensions of four compounds and the stabilizer selection could be achieved within 2 h by using this ultra-small bead milling method. Six months stability was observed for selected samples. In addition, the scalability of the ultra-small lab-scale milling was confirmed when it was conducted under optimal conditions. A simple and fast ultra-small-scale approach for nanosuspension production was established. Freeze-drying was applied to convert nanosuspensions into solid forms. Finally, freeze-dried intermediates with good redispersity and physical stability were obtained, which could be used for further application.