The two available wetting methods for twin screw granulation, namely foam delivery and liquid injection, were studied in detail by examining granule development along the screws as powder formulation and screw design were varied. Granulation profiles were determined by particle size analysis of samples along the screws collected using the screw pullout technique. Analysis of the particle size and porosity of produced granules revealed only minor differences between the two methods of wetting despite the larger dropsize of liquid injection compared to foam delivery. Excipients like microcrystalline cellulose or hydroxypropyl methyl cellulose with poor spreading properties, quantified by their specific penetration time and nucleation ratio, made the differences more apparent. The general similarities in granulation independent of wetting method implied that binder dispersion in an extruder was dominated by mechanical dispersion. Screw design (i.e., location of kneading block) had the dominant effect on the granulation process in this study. (c) 2014 American Institute of Chemical Engineers AIChE J, 61: 780-791, 2015