Abstract
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.
Introduction
Microencapsulation of bioactive compounds is a fundamental technological strategy that consists of isolating an active substance (core) within a polymeric matrix or membrane to form particles of micrometric size (1). This technique emerged from the need to protect sensitive ingredients against adverse environmental factors and to control their release at specific sites within the organism (2, 3).
Currently, its application is critical in sectors such as the pharmaceutical, food and nutraceutical industries, especially for the management of phytochemicals such as flavonoids and polyphenols. Although these compounds possess recognised antioxidant, antiinflammatory and anticancer properties, they present marked instability against light, heat and oxygen. Furthermore, their bioavailability is drastically reduced in the gastrointestinal tract due to acidic pH and the presence of enzymes and bile salts (4–6).
To overcome these biological and physico-chemical limitations, diverse encapsulation systems have been developed to maximise loading efficiency and protection (7, 8). A crucial aspect of this design is the selection of coating materials, which must be biocompatible, biodegradable and, in the case of food applications, comply with safety regulations such as the generally recognised as safe (GRAS) status of the FDA. Different studies have highlighted that the choice between natural biopolymers (proteins, starches) and synthetic ones (Eudragit, PVP) determines mechanical stability, responsiveness to pH stimuli and the controlled release of the active
compound (7, 9–12).
Among the various existing encapsulation technologies (spray drying, electrospraying, coacervation, fluidised bed), hot-melt extrusion (HME) has recently emerged as a robust and scalable alternative (13, 14). Unlike traditional methods, HME enables the formation of amorphous solid dispersions without the use of organic solvents, making it a green and continuous technology (15).
However, the implementation of HME in nutraceuticals faces significant technical challenges, mainly related to thermal degradation. Given that the process involves melting and mechanical shear, there is a risk of degrading thermolabile compounds such as phenols. Therefore, precise control of parameters such as barrel temperature, screw speed and the use of plasticisers is vital to balance polymer processability with the preservation of bioactivity (16–18).
Unlike previous reviews that focus broadly on the technique, this article provides a comprehensive and up-to-date analysis of the specific application of HME for plant-derived bioactive compounds. This review examines recent advances up to 2024, correlating critical processing conditions (temperature and shear) with encapsulation efficiency. In addition, the most effective polymers for nutraceutical matrices are discussed and relevant characterisation methodologies are consolidated, offering a clear perspective on the industrial aviability and future trends of this technology.
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Materials
Excerpt from the Table 3. Comprehensive summary of process parameters, polymeric matrices and performance outcomes in the HME encapsulation of plant-derived bioactives (2014–2024)
| Plant Source / bioactive compound | Polymer matrix (Blend) | Conditions (Temp / speed) | Key findings and performance (quantitative improvement) | References |
|---|---|---|---|---|
| I. Polyphenols, flavonoids and anthocyanins | ||||
| Quercetin/ pure quercetin | HPMC, Poloxamer 188, Soluplus, PEG 600 | 150–170 °C/ 100 rpm | Improved dissolution rate and oral bioavailability compared to pure crystalline quercetin. | (15) |
| Mulberry leaf (Morus alba) /isoquercetin, rutin | Whey protein isolate, soy lecithin, Vitamins C and E | 100 °C/ 50 rpm | Phenolic content increased from 22,12 to 31,14 mg GAE/g. Improved solubility and functional bioactivity. | (16) |
| Mulberry leaves (varieties)/ rutin, isoquercetin | Whey protein isolate, lecithin, vitamin C | 100 °C/ 50 rpm | Significant increase in biological activity. Optimized variety reached 31,14 mg GAE/g total phenolics. | (21) |
| Mulberry (Morus alba) / anthocyanins | Protein isolate, Sodium alginate, Poloxamer 188 | 80–100 °C/ 150 rpm | Hydrolysis of bound phenolics increased free content: Total phenolics reached 1109 mg/100g; Anthocyanins 247 mg/100g. | (22) |
| Citrus (orange/grapefruit)/ naringenin | PVP, polyglycerol O-50D | 180–200 °C/ 100 rpm | Aqueous solubility increased to ~15 mg/mL (200-fold higher than crystalline naringenin). | (23) |
| Epicatechin | Ethylcellulose, Eudragit L100, povidone | 160 °C/ 70–100 rpm | Enhanced solubility and effective taste masking suitable for chocolate matrices. | (25) |
| Angelica gigas Nakai / nanocomposites | HPMC (HP55, CN40H), sodium alginate | 70–100 °C/ 150 rpm | Extruded nanocomposites showed improved solubility. Phenolics: 2187 mg/100 g; Flavonoids: 165 mg/100 g. | (26) |
| Kenaf seeds / polyphenols | Seed flour, lecithin, whey concentrate | 80–120 °C/ 200 rpm | Enhanced extraction via shear: Phenolics increased from 1370 to 3342 mg/100g. | (27) |
| Scutellaria root/ baicalin | Chitosan, HPMC (25:75) | 150 °C/ 150 rpm | Tablets demonstrated controlled release of baicalin with good mucoadhesive properties. | (29) |
| Angelica gigas Nakai / phenols, flavonoids | HPMC (5 %), acetic acid (plasticizer) | 80–120 °C/ 220 rpm | Solubility improved by 65,5 %. Total phenolics reached 2832 mg/100g with enhanced bioaccessibility. | (30) |
| Mulberry (Morus alba)/ anthocyanins | Citric acid, sodium alginate | 80–100 °C/ 150 rpm | Enhanced water solubility and release rate. Anthocyanin content preserved at 331 mg/100g. | (31) |
| Polygonum cuspidatum/ resveratrol (50 %) | HPMCAS, Eudragit EPO, Soluplus | 140 °C/ 40 rpm | Solid dispersions significantly improved solubility and dissolution rate of resveratrol. | (38) |
Victor HRB, José FSD, José LHC. Trends and applications of hot-melt extrusion in the encapsulation of bioactive compounds for nutraceutical products. Plant Sci. Today [Internet]. 2026 Apr. 17 [cited 2026 Jun. 12];13(2). Available from: https://horizonepublishing.com/journals/index.php/PST/article/view/10018
