ARTcrystal® process for industrial nanocrystal production—Optimization of the ART MICCRA pre-milling step

Abstract

The ARTcrystal process is a new approach for the production of drug nanocrystals. It is a combination of a special pre-treatment step with subsequent high pressure homogenization (HPH) at low pressures. In the pre-treatment step the particle size is already reduced to the nanometer range by use of the newly developed ART MICCRA rotor-stator system. In this study, the running parameters for the ART MICCRA system are systematically studied, i.e. temperature, stirring speed, flow rate, foaming effects, size of starting material, valve position from 0° to 45°. The antioxidant rutin was used as model drug. Applying optimized parameters, the pre-milling yielded already a nanosuspension with a photon correlation spectroscopy (PCS) diameter of about 650 nm. On lab scale production time was 5 min for 1L nanosuspension (5% rutin content), i.e. the capacity of the setup is also suitable for medium industrial scale production. Compared to other nanocrystal production methods (bead milling, HPH, etc.), similar sizes are achievable, but the process is more cost-effective, faster in time and easily scale-able, thus being an interesting novel process for nanocrystal production on lab and industrial scale.