(311d) Scale up Methodology and Practical Application of Wet Bead Milling for the Production of Submicron Particles

Particle size reduction via wet bead milling of a temperature sensitive pharmaceutical material to a reproducible submicron endpoint is achievable across the Netzsch Delta Vita mill series. The reduced particle size allows for an improved dissolution rate when compared to unmilled material. Wet bead milling offers the advantage of increased heat dissipation and removal 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 smoothly scaled from lab to industrial scale.