Abstract
Solid dispersion (SD) is a technique used to improve the solubility of poorly water‐soluble compounds by dispersing them in a solid water‐friendly carrier. Current trends indicate that natural‐based alternatives are increasingly replacing synthetic carriers, benefiting the pharmaceutical industry, where they were first adopted, and paving the way for broader use in nutraceuticals and food applications, as regulations and consumer preferences drive the adoption of eco‐friendly alternatives. In the food industry, SDs can address key challenges, such as enhancing water compatibility and stabilizing sensitive compounds, thereby facilitating the effective use of natural‐based ingredients. Exploring natural carriers enables SDs to align with food industry priorities, enabling the development of functional ingredients, stable natural colorants, products with increased flavor retention, innovative packaging materials, and healthier, structured food analogues through Pickering emulsion technology. In this context, the review examines the path of SDs from pharma to food, beginning with a detailed examination of SD systems using both synthetic and natural carriers across the pharmaceutical, nutraceutical, and food sectors. The review concludes with an in‐depth discussion of emerging applications in the food industry, highlighting the potential of SDs to address formulation challenges and to foster sustainable, consumer‐oriented innovations in modern food systems. To advance SD applications in food systems, future research should integrate sensory evaluation and address technical, regulatory, and formulation‐performance gaps to ensure consumer‐acceptable, high‐quality innovations.
Introduction
Among the various strategies designed to enhance the bioavailability of hydrophobic compounds, SD is a preferred methodology in the pharmaceutical industry. Since its introduction in the 1960s (Nair et al. 2020; Sekiguchi and Obi 1961) and particularly named solid dispersion (SD) in the 1970s (Chiou and Riegelman 1971), SD has been widely recognized as a valuable approach for developing stable and efficient drug formulations, leading to continuous evolution and significant advancements in the field (Khan et al. 2022).
SD involves the dispersion of at least two components, commonly a hydrophobic crystalline active compound and a hydrophilic carrier, typically a polymer, where the active compound is molecularly dispersed within the polymer matrix, resulting in an amorphous structure (Mir and Khan 2017; De Mohac et al. 2020; Pasarkar et al. 2022). The chemical composition and processing techniques are crucial for designing a successful SD formulation, which can result in different structures stabilized by intermolecular interactions. SDs are commonly classified in different generations, reflecting advancements in the field since the first SD was developed in 1961 (Sekiguchi and Obi 1961). This first‐generation utilizes a crystalline carrier, producing eutectic mixtures where the melting point is lower than that of the active compound and the carrier (Tekade and Yadav 2020). The second generation introduces amorphous carriers, improving the active compound dissolution rate compared to the first generation. The major challenges associated with these systems are precipitation under supersaturation and recrystallization of the active compound (Sanklecha 2020). Third‐generation SDs, which have generated significant interest over the last decade, utilize carriers with emulsifying properties or a mixture of amorphous polymers and emulsifiers. This advancement addresses the disadvantages of the second generation, further enhancing the dissolution rate of the active compound and improving its physical and chemical stability (Tambosi et al. 2018; Budiman, Lailasari, et al. 2023).
The fourth generation comprises controlled‐release systems of active compounds with short half‐lives, using hydrophobic or swellable polymers to slow the release (Srividya and Ghosh 2025). Recent research has suggested a fifth generation involving multicomponent SDs. These systems, designed to further enhance SD performance, consist of one or more hydrophobic active compounds dispersed within a carrier that comprises more than two polymers (De Mohac et al. 2020).
Another classification categorizes SDs by dispersion type. It comprises binary SDs, ternary SDs, and solid surface dispersions. Binary SDs are a dual‐phase system, including a hydrophobic active compound and a hydrophilic carrier. Ternary SDs comprise three components, corresponding to the addition of a surfactant to the active compound and carrier (Saberi et al. 2023). Solid surface dispersion is a system where the active compound is selectively deposited onto the carrier surface. This configuration often yields smaller particle sizes, thereby enhancing dissolution rates and bioavailability (Sanklecha 2020).
SDs offer higher solubility and dissolution rates, as well as improved stability of hydrophobic active compounds, making them appealing systems for drug formulation (Huang and Dai 2014). This technology can be applied to various compounds, enhancing their performance while offering effective, continuous, scalable production opportunities. In this context, SDs are widely used at an industrial scale for their process efficiency and the convenience of producing a final product in powder form, with their small particle sizes also contributing to promoting dissolution and increasing absorption rates (Joy et al. 2020; P. Tran et al. 2019).
Maintaining the chemical and physical stability of SDs during storage can be challenging. In fact, the literature frequently highlights the limitations of carrier hydrophilic polymers, as they often absorb moisture, reversing the transition from the amorphous to the crystalline state and thereby decreasing solubility and dissolution rates (Dhande et al. 2021; Cid et al. 2019). Thus, it is essential to properly select the chemical systems used and assess their stability during production and storage.
The evolution of SD carriers began with the use of synthetic polymers, such as polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG), which offered improved stability and controlled release. Further advancements led to the use of cellulose derivatives and enteric polymers to enhance the molecular interaction between the active compound and the polymeric carrier. The progress then faced a growing preference for natural, biocompatible polymers such as chitosan and cyclodextrins, which offered enhanced safety and compatibility (S. Jain et al. 2024).
Building on this trend, significant effort has been dedicated to understanding and refining SD methodology to achieve optimal formulations for practical applications (Wang et al. 2023). The pharmaceutical industry, known for its pioneering innovations, has been a primary adopter, commercializing numerous products that use SDs to improve drug efficacy. Thereafter, as the pharmaceutical sector advanced, SD steadily expanded into other areas. Recognizing the potential of SD to address solubility, bioaccessibility (the fraction of a bioactive compound available for absorption), and bioavailability (the amount effectively absorbed to reach the site of action), areas such as cosmetics, nutraceuticals, and food began adopting this approach. For example, in the nutraceutical field, SD has helped to improve the absorption and effectiveness of dietary supplements (Colombo et al. 2021). Similarly, SD has been applied to develop functional food ingredients with enhanced properties (Tomas et al. 2024).
This expanding use of SD beyond the pharmaceutical sector highlights its versatility and effectiveness in addressing formulation challenges across diverse sectors. It reflects a continuous effort to innovate and apply scientific advancements to meet the evolving needs of different industries. In line with this, the present work offers an overview of the transition of SD from pharmaceutical to food applications. It reviews recent research and key developments in this field, paving the way for this transition.
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TABLE 1. Solid dispersions prepared with synthetic and natural carriers for the nutraceutical area, highlighting the type of carrier, active ingredient, preparation method, and principal results.
Synthetic carriers
| Carrier | Active compound | Preparation method | Main results | Reference |
|---|---|---|---|---|
| Eudragit | Resveratrol | Spray drying | SD improved the solubility, maintaining the supersaturated state for 48 h with no resveratrol precipitation | Ha et al. (2021) |
| Eudragit E PO | Centella asiatica extract | Solvent evaporation—vacuum drying | SD significantly enhanced the solubility and sustained release of the glycosides asiaticoside and madecassoside | Wannasarit et al. (2020) |
| Eudragit E PO | Resveratrol | Freeze‐drying | SD increased resveratrol solubility by 8 to 12 times, improved intestinal permeability, and showed a 5 times higher dissolution rate compared to the pure form and the physical mixture | Almeida et al. (2024) |
| Eudragit E PO, PEG 6000, Kollidon 30 (PVP K30), and Soluplus | Resveratrol | Solvent evaporation—room temperature | SD with PVP K30 and Soluplus showed better miscibility and stability but low dissolution rate, while Eudragit E PO improved dissolution about 13 times without changing crystallinity or stability after storage | Yu et al. (2023) |
| HPMCAS, HPMCP, Soluplus, cellulose acetate, and Gelucire 50/13 | Epigallocatechin gallate | Freeze‐drying | The physical stability and dissolution rate, especially with Soluplus, were improved | Cao, Teng, and Selbo (2017) |
| Hydroxypropyl cellulose‐SSL | Nobiletin | Freeze‐drying | SD improved the solubility and oral bioavailability | Nihei et al. (2021) |
| PEG 6000 and F68 | Resveratrol | Melting method | SD raised the solubility and dissolution rate significantly | L. Wang et al. (2021) |
| PEGs 4000 and 6000 | Moringa oleifera leaf powder | Freeze‐drying, melting, solvent evaporation—oven drying, and microwave irradiation | SDs of Moringa extract (partially amorphous state) provided better thermal stability than the pure compound | Tafu and Jideani (2021) |
| Pluronic F127 | Apigenin | Spray drying | SD at a 1:4 (apigenin:Pluronic F127) ratio significantly improved dissolution rate and bioavailability (through indicated hydrogen bonding between the components) | Altamimi et al. (2018) |
| Pluronic F127 | Apigenin | Kneading, melting, and microwave irradiation | SD improved the dissolution rate and oral absorption | Alshehri et al. (2019) |
| PVP K10 | Resveratrol | Solvent evaporation—vacuum drying | SDs revealed stable amorphous or partially crystalline systems, with molecular‐level distribution and hydrogen bonding networks that prevent recrystallization | Pajzderska et al. (2025) |
| PVP K30 and Eudragit E PO | Ginger extract | Solvent evaporation—vacuum drying | SD increased the solubility of the ginger extract. Raft‐forming system included sodium alginate and HPMC | Matchimabura et al. (2024) |
| PVP K30 and poloxamer | Vitamin D3 | Solvent evaporation—room temperature | SD improved cholecalciferol solubility, maintained its amorphous form and stability, showed no adverse effects on intestinal cells, and enhanced the dissolution rate of HPMC capsules | Rawat et al. (2023) |
| PVP K30 and PVPVA64 | Pterostilbene | Dry ball milling | SDs improved the solubility, release profile, permeability, antioxidant properties, and neuroprotective effects of pterostilbene | Rosiak et al. (2024) |
| PVP K30 | Myricetin | Spray drying | The solubility of myricetin was improved up to 50% of the nutraceutical load | Mureşan‐Pop et al. (2017) |
| PVPVA64 and Soluplus | Piperine | Freeze‐drying, solvent evaporation—oven drying, and microwave irradiation | SDs prepared with PVPVA64 and Soluplus improved solubility and stability, with ternary systems showing superior performance over binary ones | Imam et al. (2025) |
Natural carriers
| Carrier | Active compound | Manufacture technique | Main results | Reference |
|---|---|---|---|---|
| Arabinogalactan | Curcumin | Dry ball milling | SD significantly increased curcumin's solubility, stability, and bioavailability | Q. Zhang et al. (2019) |
| Chitosan | Abietic acid | Solvent evaporation—agitation at room temperature | SD exhibited enhanced antioxidant and antimicrobial properties (particularly at 1:1 abietic acid:chitosan ratio) | Cuzzucoli Crucitti et al. (2018) |
| Chitosan | Apigenin | Spray drying | SD showed enhanced drug release, improved antimicrobial and antioxidant properties, and potential anticancer effects | Alali et al. (2025) |
| Chitosan | Quercetin | Dry ball milling | SD enhanced the dissolution rate and increased 2.25 times the bioavailability compared with pure quercetin | Han et al. (2021) |
| Erythritol | Oleocanthal | Melting method | SD increased the dissolution rate, improving the nutraceutical properties of oleocanthal | Tajmim et al. (2021) |
| Microcrystalline cellulose | Moringa oleifera leaf extract | Freeze‐drying | SD improved the solubility and physical‐mechanical characteristics of moringa extract (1:2 ratio moringa:cellulose ratio) | Rani et al. (2023) |
| Myricetin (co‐former) | Curcumin | Freeze‐drying | SD improved curcumin dissolution in intestinal fluid and its bioavailability, with enhanced antioxidant activity | J. Zhang et al. (2025) |
| Modified sprouted rice | Curcumin | Melting method | SD enhanced the dissolution rate of curcumin | Luu et al. (2019) |
| Undaria pinnatifida polysaccharides | Ellagic acid | Dry ball milling | SD significantly enhanced ellagic acid's solubility, dispersibility, and biotransformation efficiency and improved microbial accessibility | Li et al. (2023) |
| Xylitol | Oleocanthal | Melting method | SD enhanced the dissolution rate and effective taste masking, potentiating in vivo anti‐breast cancer activity | Qusa et al. (2019) |
| α‐Glycosylated stevia | Sesamin | Spray drying | SD increased the solubility and bioavailability, improving the potential of the nutraceutical properties | Sato et al. (2017) |
| β‐Cyclodextrin | Lycopene | Freeze‐drying | SD exhibited promising solubility for osmotic‐controlled delivery (1:5 lycopene:𝛽‐cyclodextrin ratio) | N. Jain et al. (2014) |
| β‐Cyclodextrin | Lycopene | Solvent evaporation—vacuum followed by oven drying | SD improved the thermal, light stability and antioxidant activity of lycopene | H. Wang et al. (2019) |
Synthetic/Natural carriers
| Carrier | Active compound | Manufacture technique | Main results | Reference |
|---|---|---|---|---|
| PVP K30 and mannitol | Ellagic acid | Solvent evaporation—vacuum drying | SDs enhanced the solubility and stability of ellagic acid under stress conditions | Kawoosa et al. (2025) |
| Sodium alginate, Pluronic | Apigenin | Dry ball milling | SD, particularly Pluronic F‐127‐based, significantly improved apigenin's solubility, stability, and antioxidant activity | Rosiak et al. (2025) |
| F‐68, Pluronic F‐127, PVP K30, and PVPVA64 | Apigenin | Dry ball milling | SD, particularly Pluronic F‐127‐based, significantly improved apigenin's solubility, stability, and antioxidant activity | Rosiak et al. (2025) |
Exipients mentioned in the paper: Eudragit E PO, Kollidon 30, Soluplus, Gelucire 50/13, PVP K10, PVP K30, alginates
Rezende SC, Santamaria-Echart A, Dias MM, Barreiro MF. Solid Dispersions as a Tool for Innovation in the Food Industry: A Path From Pharma to Food. J Food Sci. 2026 Feb;91(2):e70917. doi: 10.1111/1750-3841.70917. PMID: 41709633; PMCID: PMC12917352.
