The interfacial bonding strength (IBS) of four different layer combinations between microcrystalline cellulose (MCC) and lactose (Lac), i.e., MCC/MCC, Lac/Lac, MCC/Lac and Lac/MCC (1st/2nd) was assessed. In these studies, various first layer (P1) and second layer compaction pressures (P2) were used to test the hypothesis that IBS is controlled by bonding area (BA) and bonding strength (BS) interplay at the interface. The BA was evaluated by measurement of the surface waviness and porosity, while BS was assessed by the tablet strength at zero porosity. Lower P1 leads to higher porosity of the first layer, and higher P2 generally leads to greater surface waviness at the interface, both favor a larger BA and thereby higher IBS. However, higher P2 causes a larger difference in radial expansion when the two layers differ, which weakens IBS. The materials in the two layers determine BS, which follows the descending order of MCC/MCC > MCC/Lac (Lac/MCC) > Lac/Lac. The trends in the effects of these factors on IBS support the hypothesis. (C) 2019 Elsevier B.V. All rights reserved.