Punch sticking is a common phenomenon in tablet manufacturing, often leading to tablet defects and compromise product quality. A thorough understanding of the sticking mechanism is essential to optimize the tablet production process. The aim of this study was to investigate the influence of formulations and punch properties on sticking. Seven model active pharmaceutical ingredients (APIs) (i.e., ibuprofen, aspirin, paracetamol, metronidazole, diltiazem, diclofenac, and cefuroxime) with various melting points and particle sizes were used to evaluate their propensity for sticking. The APIs stuck to punch were extracted and quantified using UV spectroscopy. The impact of fillers (i.e., microcrystalline cellulose, lactose monohydrate, dicalcium phosphate, pregelatinized starch, cellactose) and lubricants (i.e., magnesium stearate, stearic acid, aerosil, talc) were investigated. Additionally, the role of punch cup geometry (i.e., flat, standard concave, and deep concave) and punch materials was also investigated to determine their influence on sticking behaviour. Experimental results showed that the APIs with either a high melting point or small particle size have a lower tendency to stick. The differential scan calorimetry plots and X-ray diffraction graphs revealed changes in the crystalline structure due to compaction, which increased the tendency to stick. The excipients and API particle size influencede the degree of sticking. Chromium nitride-coated punches did not eliminate potential sticking at low compaction speeds. The flat-face punch demonstrated a higher sticking tendency than the concave punch. The factors contributing to sticking during tablet manufacturing were either ingredient properties, tableting parameters or both. Formulations containing MCC as a filler and utilizing deep concave punch were found to significantly reduce sticking tendencies compared to those with dicalcium phosphate filler and flat-faced punches.

Polyphenols, abundant compounds found in natural sources, exhibit various biological activities, including immunomodulatory properties that can either stimulate or suppress immune responses, making them promising for therapeutic applications. However, their poor solubility, low bioavailability, rapid metabolism, and non-specific distribution require advanced drug delivery strategies to overcome limitations in clinical translations. Therefore, nano-drug delivery systems have been intensively studied to explore the full therapeutic potential of polyphenols. Distinct from conventional paradigms where polyphenols serve solely as active compounds, this review advances the concept of polyphenol-based nanomedicine as dual-functional platforms: bioactive structural components and intrinsic immune modulators. Recent strategies to improve the loading efficacy of polyphenols, enhance their cellular uptake, prolong circulation, and enhance specific delivery based on those nanocarriers are emphasized. In addition, polyphenol-based nanoparticles, in which polyphenols serve as structural components, were also studied as self-therapeutics or multifunctional nanocarriers for drug delivery. We intensively focus on their immunomodulatory applications and highlight their potential in preclinical as well as clinical settings for the treatment of various diseases and therapeutic purposes, including autoimmune diseases, cancer immunotherapy, vaccination, inflammation, and infectious diseases. Although polyphenol nanoparticle development has made significant advances, there remain challenges in formulation stability, unclear in vivo toxicity profiles, and clinical translation. Further studies on optimizing nanoparticle design and assessing long-term toxicity are necessary to materialize their application. A combination of polyphenol nanoparticles with other immunotherapies may promise a pronounced efficacy and safety profile.