The scale-up of the API crystallisation becomes particularly important if a high degree of control is required over PSD or any other physical property. Scale-up of crystallisation is non-trivial, therefore, the proven acceptable range for such a property should be as wide as possible in the formulation.
Example of Skills and Experience
The Specific Surface Area (SSA) for an inhaled API needed to be reproduced on transfer into manufacturing to ensure adequate powder flow prior to micronization. A number of different scale-up parameters were investigated experimentally maintaining geometric similarity to the manufacturing plant. Identical PSD was demonstrated between pilot and manufacturing scale using constant shear rate. The process is now operated successfully for commercial supply.
For an example of this approach see https://doi.org/10.1021/op040013n