Wet Media Milling Preparation and Process Simulation of Nano-Ursolic Acid

<b>Background/Objectives</b>: Pharmaceutical preparation technologies can enhance the bioavailability of poorly water-soluble drugs. Ursolic acid (UA) has been found to possess anti-cancer and hepatoprotective properties, demonstrating its potential as a therapeutic agent; however, its hydrophobicity and low solubility present challenges in the development of drug formulations. This study investigates the preparation of a nano-UA suspension by wet grinding, researches the influence of process parameters on particle size, and explores the rules of particle breakage and agglomeration by combining model fitting. <b>Methods</b>: Wet grinding experiments were conducted using a laboratory-scale grinding machine. The particle size distributions (PSDs) of UA suspensions under different grinding conditions were measured using a laser particle size analyzer. A single-factor experimental design was employed to optimize operational conditions. Model parameters for a population balance model considering both breakage and agglomeration were determined by an evolutionary algorithm optimization method. By measuring the degree to which UA inhibits the colorimetric reaction between salicylic acid and hydroxyl radicals, its antioxidant capacity in scavenging hydroxyl radicals was indirectly evaluated. <b>Results</b>: Wet grinding process conditions for nano-UA particles were established, yielding a UA suspension with a D50 particle size of 122 nm. The scavenging rate of the final grinding product was improved to three times higher than that of the UA raw material (D50 = 14.2 μm). <b>Conclusions</b>: Preparing nano-UA suspensions via wet grinding technology can significantly enhance their antioxidant properties. Model regression analysis of PSD data reveals that increasing the grinding mill's stirring speed leads to more uniform particle size distribution, indicating that grinding speed (power) is a critical factor in producing nanosuspensions.