Trends and applications of hot-melt extrusion in the encapsulation of bioactive compounds for nutraceutical products

The encapsulation of plant-derived bioactive compounds, such as polyphenols and flavonoids, constitutes an essential strategy to mitigate their physico-chemical instability against oxidative factors, light and pH variations in the gastrointestinal tract. While conventional techniques like spray drying are common, they often present limitations related to the use of organic solvents and discontinuous processing. Hot-melt extrusion (HME) has emerged as a sustainable, continuous and solvent-free technology; however, its viability for processing thermosensitive molecules has historically been questioned due to the thermal stress involved. Unlike previous reviews, this study integrates a bibliometric analysis with a critical technical evaluation specifically focused on strategies to preserve bioactivity under shear conditions. A systematic review of 148 studies published between 2014 and 2024, retrieved from Scopus, Web of Science (WoS) and PubMed, was conducted, evaluating the interaction between process parameters and polymeric matrices. The results reveal that HME facilitates the formation of stable amorphous solid dispersions through intermolecular interactions that prevent active recrystallisation. It was demonstrated that rigorous control of barrel temperature, screw speed and residence time allows for the processing of thermolabile compounds with minimal degradation, achieving significant improvements in solubility and bioavailability compared to pure crystalline forms. In conclusion, HME consolidates itself as a robust and efficient industrial alternative for the development of nutraceuticals. The future perspective of this technology lies in the research of new biopolymers with generally recognised as safe (GRAS) status and advanced plasticisers that optimise bioactive loading and allow for customised release profiles.