Table 1.

Hypotheses and working mechanism of “addition of lactose fines” [6, 7].

Hypothesis	Working mechanism
Active sites hypothesis	Fines engage so-called “active sites” (more adhesive sites) on carrier surface, leaving only weaker binding sites (less adhesive sites) accessible for the drug particles to bind to.
Agglomeration hypothesis	Fines materialize agglomerates, multilayers with drug particles, which are hypothetically more easily isolated from the carrier surface.
Buffer hypothesis	Fines coarser than the drug particles might work as a buffer between moving carrier particles and shelter drug particles from press-on forces during mixing.
Fluidization hypothesis	Fines enhance the tensile strength of the powder mixture, which enhances the minimum fluidization velocity (MFV) required for fluidization and therefore the energy available for dispersion.
Case-dependent hypothesis	Contrary to the all above hypothesis, fines do not always enhance the aerodynamic performance of a DPI which is concluded by the formulation and dispersion situations.