Manufacturing nano-sized powders using salt- and sugar-assisted milling

There is need for non-toxic, biocompatible nanoparticles for various applications in the field of nano-engineering. Reduction of size to nano-scale is required to enhance material properties such as bioavailability, drug release and dissolution kinetics. Dry media assisted milling was optimized for two materials; a soft lipophilic drug, fenofibrate and a relatively hard material, nanodiamond. Nanoscale particles are especially important for hydrophobic substances due to their unacceptably slow dissolution kinetics in aqueous gastrointestinal tract-type environments, which has resulted in inefficient oral drug delivery. Fenofibrate, a popular cholesterol reducing drug, currently produced in micron size, was milled with salt/sucrose to yield 500 nm particles. The dry media was removed by rinsing with deionized (DI) water and dried at room temperature. The powder was characterized using scanning electron microscopy (SEM) and particle size analysis. In vitro dissolution studies resulted in improved kinetics. Various surfactants including sodium dodecyl sulfate (SDS) and cyclodextrin were investigated to achieve an increased dissolution rate. There has been recent interest in nanodiamond particles, typically ~5 nm in diameter, as drug delivery vehicles in chemotherapy. However, the tendency of nanodiamond to aggregate into micron sized clusters is a major challenge in all these applications. Current methods that successfully achieved monodispersions of nanodiamond in aqueous media have been unable to remove toxic contaminants introduced during the synthesis process. Nanodiamond powders were milled with salt/sucrose in a dry environment to yield primary particles embedded in a salt/sucrose matrix. A parametric study optimized the protocol, confirmed by particle size results revealing clusters of 2-3 particles which are desirable for many applications. The milling parameters were optimized for fenofibrate and nanodiamond as follows; Fenofibrate Milling duration = 180 min Speed of rotation = 500 rpm Fenofibrate to media ratio = 1:12 (sodium chloride), 1:7 (sucrose) Nanodiamond Milling duration = 90 min Speed of rotation = 500 rpm Nanodiamond to media ratio = 1:7 Milling is an effective and economical technique, which can be easily implemented as a grading facility in most of the existing production processes.