Milling and micronization are used to make particles of inhalable size (1-5um), to increase dissolution rate and to ensure good content uniformity in oral formulations particularly where the dose is low.
Common problems include feeding into the micronizer, and amorphization and instability post size reduction.
Example of Skills and Experience
An API with needle-like morphology exhibited extremely poor flow into a micronizer leading to blockages and poor yields. The API step was redesigned with the help of Process Analytics, so that the particle aspect ratio was reduced and powder flow enhanced. In addition, a flexible walled feeder was used to prevent powder bridging in the hopper. As a result, micronisation was achieved reproducibly at manufacturing scale.
•https://doi.org/10.1016/S0378-5173(98)00179-3 gives an example of amorphization of salbutamol as a result of micronization.