Role of Milling Parameters and Particle Stabilization on Nanogrinding of Drug Substances of Similar Mechanical Properties

The feasibility and efficiency of wet-nanogrinding of three drug substances (miconazole, itraconazole, etravirine) with similar elastic and plastic properties proved to depend primarily on the adequate electrostatic and steric stabilization of the nanoparticles and the specific energy input. Particle stabilization was provided by sodium dodecyl sulfate (SDS) and hydroxypropylcellulose. The specific energy input was defined by the grinding time, grinding bead size, and stirrer tip speed. Miconazole and itraconazole exhibited similar milling behavior, whereas etravirine nanosuspensions revealed agglomerates and increasing viscosity with increasing specific energy input. Agglomeration and viscosity increase were successfully counteracted by increasing the SDS concentration in the nanosuspension from 0 to 0.125 %. Under the provision of proper particle stabilization, the three drug substances could be nanosized to a mean size of ∼ 130 nm, with 90 % of all particles being smaller than ∼ 250 nm.