The effect of particle size on interfacial bonding strength (IBS) of bilayer tablets was studied using microcrystalline cellulose (MCC) and lactose anhydrate. When MCC is in the first layer, IBS is generally lower and more sensitive to particle size and mechanical properties of the second layer material. In contrast, when lactose is in the first layer, the IBS is higher and less influenced by either of these factors. On the other hand, the use of MCC in the second layer leads to higher IBS than lactose. The dependence of IBS on material and particle size can be explained by bonding area (BA) - bonding strength (BS) interplay. IBS generally increases with increasing BA, which is favored by larger particles in the second layer. However, variations in particle size of the first layer powder did not significantly affect IBS. (C) 2019 Elsevier B.V. All rights reserved.