Unlike shear mixing in twin-screw extrusion, VCM leverages diffusion for mixing. The smaller the particles, the more dominant the transfer via diffusion gets compared to shear. Cryogenic ball milling is an excellent option to reduce particle size and homogenize the powder mixture. This will give extrusion-like VCM results without the risk of shear degradation.
With batch sizes up to 5 grams and losses of less than 10 mg, cryogenic ball milling is an excellent process for micronization and powder homogenization before the VCM process. Nevertheless, for small quantities, a lossless homogenization is preferred. Thin film casting is a powerful method of mixing API and polymer with a minimum amount of solvent.
The thin layer dries within minutes after dispersing the solution on a glass plate. The film is removed with a razor blade and can be shaped with the VCM process.