Nanocrystal Preparation of Poorly Water-Soluble Drugs with Low Metal Contamination Using Optimized Bead-Milling Technology.

Nanocrystal preparation using bead milling is an important technology to enhance the solubility of poorly water-soluble drugs. However, there are safety concerns regarding the metal contaminants generated during bead milling. We have previously reported optimized bead-milling parameters that could minimize metal contamination and demonstrated comparable performance to NanoCrystal, a world-leading contamination-free technology.

Development of Novel Bead Milling Technology with Less Metal Contamination by pH Optimization of the Suspension Medium.

To develop novel contamination-less bead milling technology without impairing grinding efficiency, we investigated the effect of the formulation properties on the grinding efficiency and the metal contamination generated during the grinding process. Among the various formulations tested, the combination of polyvinylpyrrolidone and sodium dodecyl sulfate was found to be suitable for efficiently pulverizing phenytoin. However, this stabilization system included a relatively strong acid, which raised the concern of possible corrosion of the zirconia beads.