(725d) Scale up Methodology and Practical Application of Wet Bead Milling for the Production of Nano and Micro Sized Particles

Particle size reduction via wet bead milling of pharmaceutical materials to a reproducible nano and micro sized particle endpoint is achievable across the Netzsch Delta Vita mill series. The controlled particle size allows for a sustained long-acting release of the active pharmaceutical ingredient to a patient to reduce the number of doses in a given year. Wet bead milling offers the advantage of increased heat dissipation and removal for temperature sensitive products when compared to a dry milling process. A total energy model approach was used to properly scale the process while geometrically scaling equipment and holding key process variables including formulation composition, agitator tip speed, and bead characteristics, among other parameters, constant between scales. An advantage of scaling with constant tip speed is that the power and heat transfer surface area also scale by the diameter of the mill which results in similar cooling across scales thereby avoiding unwanted surprises for temperature sensitive products during scale up. The milling process was successfully scaled from lab to industrial scale. A case study will be presented showing the experimental design, scale-up calculations, and results.