Adhesion of the powders to the punches is a common issue during tableting. This phenomenon is known as sticking and affects the quality of the manufactured tablets. Defective tablets increase the cost of the manufacturing process. Thus, the ability to predict the tableting performance of the formulation blend before the process is scaled-up is important. The adhesive propensity of the powder to the tableting tools is mostly governed by the surface surface adhesive interactions. Atomic force microscopy (AFM) colloidal probe is a surface characterization technique that allows the measurement of the adhesive interactions between two materials of interest. In this study, AFM steel colloidal probe measurements were performed on ibuprofen, MCC (microcrystalline cellulose), alpha-lactose monohydrate, and spray-dried lactose particles as an approach to modeling the punch particle surface interactions during tableting. The excipients (lactose and MCC) showed constant, small, attractive, and adhesive forces toward the steel surface after a repeated number of contacts. In comparison, ibuprofen displayed a much larger attractive and adhesive interaction increasing over time both in magnitude and in jump-in/jump-out separation distance. The type of interaction acting on the excipient steel interface can be related to a van der Waals force, which is relatively weak and short-ranged. By contrast, the ibuprofen steel interaction is described by a capillary force profile. Even though ibuprofen is not highly hydrophilic, the relatively smooth surfaces of the crystals allow "contact flooding" upon contact with the steel probe. Capillary forces increase because of the "harvesting" of moisture due to the fast condensation kinetics leaving a residual condensate that contributes to increase the interaction force after each consecutive contact. Local asperity contacts on the more hydrophilic surface of the excipients prevent the flooding of the contact zone, and there is no such adhesive effect under the same ambient conditions. The markedly different behavior detected by force measurements clearly shows the sticky and nonsticky propensity of the materials and allows a mechanistic description.