Background: Microfluidization is one emerging size reduction technique in the field of inhalation; previous works  have suggested modelling equations for the involved comminution profiles, but evaluation of such mathematical relationships across different compounds is still missing.
Methods: Size-reduction of three compounds, namely fluticasone propionate (FP), salmeterol xinafoate (SX) and mometasone furoate anhydrous (MF), was performed by microfluidization of suspensions using the same model processor and operating conditions. In all cases, the final particle size after processing was within a typical inhalation range (1.5 m < Dv50 < 2.5 m). After generating the data, different candidate models were identified through Partial Least Squares (PLS) regressions and, afterwards, fine-tuned by reducing the number of fitting parameters in order to minimize over-fitting phenomena and facilitate a potential mechanistic interpretation of the found relationships.
Results: The obtained results show that the size-reduction profiles of the different compounds, although apparently similar, cannot be entirely captured by previous models , requiring more flexible mathematical relationships; additionally, it was also found that the penalty (decrease of R2 value) associated to the reduction of the number of fitting parameters depends heavily on the pre-set equation structure, a key indicator for the selection of the best performing model.
Conclusions: The intrinsic behaviour of microfluidization processes, across different top inhalation compounds, can be accurately captured, provided that an appropriated model structure is adopted; the suggested equation enables a mechanistic interpretation, where one of the fitting parameters is hypothesized to be related with the physical intrinsic properties of the compounds.