Solid dosage forms are typically prepared by blending the active pharmaceutical ingredient (API) with excipients, granulating to improve flow and then compressing into a tablet to achieve the intended potency and dose uniformity. Physicochemical properties of the API can present challenges during these processes. API may adhere to surfaces, form agglomerates that can be difficult to control, or even make the tablet unprocessable. Interaction between particles and surfaces are affected by long range (~100 nm) interparticulate forces (van der Waals, electrostatic, capillary, and gravitational) and short range (< 1 nm) intermolecular surface forces (dipole and hydrogen bonds). Interparticulate forces are dependent on the particle diameter, morphology (effective interaction area), material properties (molecular density), and environmental conditions (moisture). Surface forces are dependent on the opportunity to form chemical bonds. A case study will be presented in which API adhesion and agglomeration were observed. A variety of techniques were used to characterize the API to identify the cause of these characteristics, including particle size, surface area, morphology, hygroscopicity, surface contact, polymorph, surface free energy, acid-base numbers, and tableting characteristics. Additionally, formulation and processing strategies to minimize these effects will be presented.