“…10 The extent of the flow improvements for very fine ibuprofen powders that were simultaneously dry coated as compared with uncoated ones was outstanding, for example, flow function coefficient (FFC; a significant measure of flow property based on shear testing 11 ) for 10 :m ibuprofen increased 10 from about 1 to 6, which is a significant achievement as compared with that observed in dry coating performed without micronization, [12][13][14][15][16] for example, similar sized acetaminophen powder had FFC of about 2 and after dry coating increased to a little over 3. 15,17 Thus, it appears that the flow improvement phenomena because of dry coating during milling may be somewhat different, and in addition to silica creating separation, or more precisely, nanoscale surface roughness, 3,13 it may also be reducing overall surface energy as well as surface energy heterogeneity via passivating high-surfaceenergy sites on milled ibuprofen powders, leading to significantly improved flow properties. Accordingly, the objective of this paper is to examine this intriguing possibility through a systematic investigation of the influence of dry coating on surface energy of milled pharmaceutical crystals, in particular, the reasons for very high cohesion of milled powders in contrast to the improvements observed after dry coating.…”