Top-down method for lab-scale production of nanocrystals of active molecules: Formulation approach and selection of optimal process parameters

Drug nanocrystals represent nanosized particles of a pharmaceutical active ingredient with an average diameter below 1000nm, commonly formulated as aqueous nanosuspensions with appropriate stabilizer. As the number of poorly soluble drugs is increasing, nanocrystals have become very interesting, due to the wide range of application possibilities. Curcumin was used as a model substance in this work. Even though it has many proven positive effects, due to its physicochemical issues, its possibilities have not been fully exploited. In this context, nanocrystals seem promising delivery systems. The main goal of this work was to select optimal conditions for the top-down method for curcumin nanosuspension production, and to perform a comprehensive characterization of selected samples using complementary methods: dynamic light scattering, polarization and atomic force microscopy, thermal analysis, antioxidant activity evaluation and release kinetics assessment. Nanosuspensions stabilized by polysorbate 80 and by combinations of polysorbate 80 and sucrose palmitate (4:1 and 2:1; curcumin:stabilizer=1:1) have shown good stability, with optimal milling time of 30min. Obtained nanocrystals were well defined, with average diameter below 200 nm, PDI was about 0.25, zeta potential was above |30| mV, and pH was around 5 for all formulations. Under selected experimental protocol, nanodispersions exhibited high antioxidant potential (IC50=0.12mg/ml). Significant differences in the release kinetics of curcumin from nanosuspensions compared to coarse dispersions was captured.