by a stochastic moment called diameter of average surface, also known as Sauter-Mean-Diameter : d3 d32 = i i .

(2) 2 i di Interestingly, this profusely used average scale is related to the above introduced index for a given total bulk volume V as: 6V d3 32
1/3

(3)

This index almost inexorably yields very large values for particulate matter, and simply reects the disparity between microscopic and macroscopic scales. However, while relatively simple chemical reactions like combustion may become independent of the microscopic shape of fragments as far as the global index given by (3) is the same, processes involving motions, deformations and reactions of a functional material (e.g., API) delivered inside a complex living organism depend not only on the global index but also on the distribution of the individual indexes of individual particles. Furthermore, sequential steps applied after fragmentation (Fig. 3) and involving mechanical and thermal actions can be utilized to provide specic internal structure to particulate matter. Again, the stochastic nature of the resulting size distribution aects in a fundamental way the functional properties of a dispersed material, their controllability and their reproducibility. In general, a higher control on the size distribution leads to higher reproducibility in functionality[30, 31, 32, 33, 34, 35, 36, 37]. Moreover, certain functional features only appear when particle size is homogeneous or relatively narrow (e.g., time release of a certain drug, [31, 33]), or when specic sizes in specied quantities are present. In addition to all this, the fragmentation process leading to the formation of the particulate system should be smooth enough to respect the chemical functionality of constituents, and this is particularly important when dealing with fragile molecules or microorganisms. Moreover, to provide a maximum control on the particle size in certain cases that we will subsequently revise in some extent, the fragmentation may be excited by the introduction in the system of a small amount of energy at a specic frequency [30, 31]. All the above considerations still leave an open overarching question: what are the existing possible ways to optimize and functionality (e. g. maximizing homogeneity in size and shape for a given bio-availability and delivery rate of an API formulation) in a reproducible, gentle, and controllable 8