The comminution of various powders produced by either spray‐freeze‐drying (SFD) or spray‐drying (SD) on firing in a Ballistic powder injector could be evaluated quantitatively using light microscopic particle imaging. SFD lactose was damaged much less than SFD mannitol and was caused by greater mechanical strength and lower acceleration. SD lactose or mannitol showed much reduced comminution because of their low porosity. SFD lactose/mannitol/dextran 10 kDa formulations also showed less low comminution. The inclusion of catalase further reduced damage on firing. The extent of comminution on firing was found to be related to microparticle surface structure and porosity which influences both mechanical strength and acceleration. © 2010 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:4917–4927, 2010