Revisiting punch sticking in tablet compression: what do we really know?

Punch sticking remains one of the most persistent challenges in tablet manufacturing, leading to surface defects, tablet weight variability, reduced productivity, and costly process interruptions. This manufacturing issue continues to increase with the growing molecular complexity of modern active pharmaceutical ingredients (APIs), which are strongly influenced by material characteristics that promote particle-tool interactions. For instance, thermal sensitivity in low-melting compounds promotes softening under frictional heat, hygroscopicity facilitates the formation of adhesive capillary bridges, and high ductility increases the effective contact area, collectively promoting persistent material transfer to the tooling. This review consolidates current understanding of punch sticking, with particular emphasis on the three-force model describing the balance between API-punch adhesion (F_API-pun), API-API cohesion (F_API-API), and API-excipient interactions (F_API-exp). Experimental approaches used to evaluate sticking are reviewed and reorganised into a stage-wise framework comprising powder-based methods, compaction-based methods, powder residual based, and tablet-based techniques. In addition, predictive approaches employed to understand sticking behaviour are systematically summarised, together with their respective advantages and limitations, highlighting the transition toward proactive, data-driven manufacturing strategies. Importantly, key knowledge gaps are identified, including limitations in early-stage prediction, insufficient quantitative mechanistic insight into adhesion and detachment processes, material-specific variability, and the absence of dynamic models' representative of industrial operating conditions. By integrating mechanistic insight with experimental and modelling perspectives, this review establishes a structured framework to guide predictive, material-informed, and industrially relevant control of punch sticking in modern pharmaceutical tabletting.