Milling for Particle Size Reduction: Process, Equipment, and Benefits
Milling indicates a generic process to reduce the size of the primary particles. Considering the technical language used in particle size reduction, the word “milling” is designated to describe the specific process to reduce the particle size by a mechanical mill and focused on achieving a PSD for D90 between 200 and 50 microns. The milled powder maintains a good flowability compared to the micronized powder, which is more sticky and presents a higher electrostatic charge. Generally, milled powder shows a coarser and tighter particle size distribution than micronized or crude crystalline powder. Therefore, it is the most suitable powder for direct compression, capsule filling, and other oral dosage forms. In addition, it is the ideal process to avoid ultra fines particles while allowing the reduction of the D90 below 100 microns.
Mechanical Milling and Particle Size Control
Mechanical mills include any impact mills: hammer, blade, pin, or any other tool that rotates at a high-speed impact on the powder, reducing the size of the primary particles. In addition, most mills foresee a grid with defined diameter holes to allow coarser particles to remain in the milling chamber to be crushed and achieve the desired size. At the same time, the diameter of the selected holes allowed the particles with the right size to leave the mill and avoid being further reduced.
Suitability of Milling Process for Different Applications
This technology is the most suitable milling process. There is no need to improve the dissolution rate and the bioavailability property of the compound to be milled. Indeed, to enhance the bioavailability of a substance, the target PSD generally needs a D90 below 10 microns or even below 5 microns in some cases.
Temperature Control in Milling Process
For the milling equipment, one of the most critical aspects is that due to mechanical components rotating at high speed, the friction generated by the rotation of the mill rotor produces an increase in the temperature inside the mill chamber, which may affect substances that are sensitive to heat. To control the temperature of the milling chamber, it is essential to ventilate it with an inert gas like Nitrogen and to be able to control the gas temperature. The capability to measure the temperature of the gas before and after it enters the mill chamber is also significant to have complete control of the process effect on the milled powder.