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INTRODUCTION
Phytosome technology has become a versatile platform for improving the delivery of plant-derived bioactives with poor biopharmaceutical properties. Phytosomes are molecular complexes formed by specific interactions between phospholipids and phytoconstituents, which lead to greater lipid compatibility and increased membrane permeability (Barani et al., 2021; Koppula et al., 2025). Indena has used phytosome technology since the late 1980s. The products developed, such as Siliphos®, Meriva®, and Greenselect® Phytosome®, have proven to be superior in absorption and therapeutic efficacy compared with traditional herbal extracts (Dwivedi et al., 2023). Many phytochemicals have inherent properties such as low aqueous solubility, low permeability, chemical instability, rapid metabolism, and extensive first-pass elimination, which affect their oral bioavailability and therapeutic efficacy, contributing to the growing interest in phytosomal systems (Drescher & van Hoogevest, 2020). To overcome these problems, various lipid-based delivery systems have been developed, including liposomes, transferosomes, ethosomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, and micelles (Singh et al., 2017). Phytosomes are a unique way, as the phytoconstituent does not just get entrapped in a carrier but forms a molecular complex with phospholipids. This unique structural configuration leads to better absorption, greater stability and favourable pharmacokinetic behaviour (Kavatagimath et al., 2026). In recent investigations, new sources of phospholipids, multifunctional hybrid systems, and surface-modified systems have been developed, extending the scope of phytosome technology in terms of stability, targeting, and therapeutic performance (Karpe et al., 2025). Most of the available reviews, however, focus on formulation strategies, individual phytochemicals, or specific therapeutic applications. By contrast, a thorough description of the formulation principles and recent advances in translating the concepts is still lacking. Hence, the present review offers an updated and comprehensive overview of phytosome technology by connecting formulation science with translational and industrial aspects, thus outlining the current advancements and future potential for designing next-generation phytopharmaceutical and nutraceutical delivery systems.
DISTINGUISHING FEATURES OF PHYTOSOMES
Phytosomes have several unique characteristics that set them apart from traditional lipid-based delivery systems. The difference between liposomes, transferosomes, ethosomes and niosomes, where the active compound is physically entrapped in the vesicles, and phytosomes is that the bioactive is an integral part of the carrier system and is formed by molecular association of phytoconstituents with phospholipids, mainly phosphatidylcholine (Dwivedi et al., 2023). The significant structural and functional difference between phytosomes and other lipid-based carriers is highlighted in Figure 1 and summarised in Table 1. Conventional vesicular systems rely on vesicle integrity and drug retention. However, they are prone to drug leakage, fusion, aggregation, and storage instability (Almuqbil & Aldhubiab, 2025; Lee, 2020).
In the same way, solid lipid nanoparticles, nanostructured lipid carriers, and micelles improve bioavailability by physically entrapping the drug in lipid matrices or surfactant assemblies, where drug release depends on matrix properties and partitioning behaviour (Mohammed et al., 2023; Nayak et al., 2025; Perumal et al., 2022). However, phytosomes increase stability and bioavailability through phospholipid complexation, providing better membrane affinity and gastrointestinal absorption (Gaikwad et al., 2021). This particular molecular organisation provides insight into the individual components involved in the formation of phytosomes and their role in formulation performance.
Components Used In Phytosome Formulation
Phospholipids
, which are amphiphilic biomolecules, consist of a glycerol backbone, two hydrophobic fatty acid chains, and a phospholipid head group, forming the basic structural components of biological membranes. In phytosomes, phospholipids, mainly Phosphatidylcholine (PC), form hydrogen-bond mediated complexes with phytoconstituents, which enhance the lipid compatibility, membrane permeation, gastrointestinal absorption and oral bioavailability of poorly soluble herbal bioactives (Figure 2) (Lu et al., 2019). Moreover, phospholipids provide excellent emulsifying properties, biocompatibility, and stability, which in turn lead to better therapeutic efficacy of phytosomal formulations (Gnananath et al., 2017). The most commonly used phospholipids are Soybean Phosphatidylcholine (SPC, ≥90-95% purity), Hydrogenated Soybean Phosphatidylcholine (HSPC, ≥95% purity), Egg Phosphatidylcholine (EPC, ≥90-99% purity) and Phosphatidylserine (PS, ≥98% purity) (Le et al., 2019). According to their sources, phospholipids used in phytosome formulations can be classified as plant-derived, animal-derived, microbial, or synthetic or semi-synthetic, each with distinct compositional and functional properties. Plant-derived phospholipids derived from soybean, sunflower and rapeseed are the most used because of their biocompatibility, cost-effectiveness and their capacity to form stable complexes with phytoconstituents and phospholipids. Nevertheless, with their high level of unsaturation, they are prone to oxidative degradation (Gnananath et al., 2017). Animal phospholipids, such as egg phosphatidylcholine and marine phospholipids with high omega-3 fatty acid content, offer superior membrane compatibility and emulsifying properties but are more expensive and less stable against oxidation (Ahmmed et al., 2020). Microbial phospholipids from yeast, fungi, algae and bacteria have become an attractive alternative that can be sustainably produced and tailored to lipid composition. However, there are still problems with large-scale production and purification (Silva et al., 2023). On the other hand, synthetic and semi-synthetic phospholipids, such as DOPC, DPPC, DSPE and HSPC, are relatively expensive but offer better purity, reproducibility and oxidative stability, which make them attractive for more advanced phytosomal systems (van Hoogevest & Wendel, 2014).
Active Phytoconstituents and Solvent
In addition to phospholipids, phytoconstituents and solvents are the other major factors influencing the formation of phytosomes. Among the most widely studied phytoconstituents are polyphenolic compounds, including flavonoids, tannins, and phenolic acids, because of their structural compatibility and strong affinity for phospholipid complexation (Gaikwad et al., 2021). Therefore, bioactive compounds such as curcumin, quercetin, rutin, and silymarin have been extensively used for incorporation into phytosomal systems because of their outstanding therapeutic activity and ability to form stable phyto-phospholipid complexes (Shriram et al., 2022). The ratio of phytoconstituent to phospholipid has a major effect on the efficiency of complex formation, and ratios of 1:1-1:2 are most frequently used to achieve optimal drug loading and complexation efficiency (Karpe et al., 2025; Pereira et al., 2016). Many studies have shown that as phospholipid content increases, entrapment and stability increase up to an optimum value. The entrapment efficiency of Tinospora cordifolia phytosomes, for example, increased from 72.34% to 95.91% as the ratio increased from 1:1 to 1:2 (Peeriga et al., 2025). Likewise, the optimised quercetin, Pongamia pinnata and curcumin phytosomes exhibited particle sizes less than 205 nm, entrapment efficiency of more than 73-94% and improved zeta potential, emphasising the importance of the ratio of components in the formulation performance (Kamireddy et al., 2025; Karpe et al., 2025; Mankan et al., 2025).
After selecting appropriate phytoconstituents and phospholipids, the choice of solvent plays an important role, as it facilitates molecular interactions and promotes stable complex formation. The solvent system directly affects the efficiency of complexation, particle size, entrapment efficiency, and formulation stability (Gnananath et al., 2017; Krishnaswami et al., 2025). Conventional solvents such as dichloromethane, acetone, and ethyl acetate have been used, but due to their toxicity and residual solvent issues, there is a growing shift toward green solvents, notably ethanol and ethanol-water mixtures (Raghav et al., 2024). Due to its good solubilising property, regulatory approval and safety, ethanol is used as a solvent for preparing phytosomes (Shriram et al., 2022). Solvent systems can be used to achieve homogeneous mixing and controlled complex precipitation, thereby enhancing drug incorporation and physicochemical properties. Efficient solvent removal methods, on the other hand, can guarantee product quality and scalability.
METHODOLOGY
Solvent Evaporation Technique
One of the most widely known and practised techniques for preparing phytosomes is solvent evaporation. It has underpinned several subsequent process changes (Lombardo & Kiselev, 2022). In this method, the phytoconstituent and phospholipid are dissolved in a common organic solvent, and the solvent is then removed stepwise to form a phyto-phospholipid complex. However, because relatively large particles are often obtained, the method is often combined with downstream size-reduction methods. For example, a pyrazoloquinolinone ligand-phospholipid complex was prepared by solvent evaporation, followed by high-pressure homogenisation, resulting in nanoparticles with sizes of 145-165 nm and entrapment efficiencies of > 96% (Stanković et al., 2025). In the same way, the use of homogenisation and ultrasonication in the preparation of Hydnora abyssinica phytosomes resulted in a particle size of 72.56±9 nm and an entrapment efficiency of 95.45±3.20% (Daba et al., 2024). These studies show the adaptability of solvent evaporation and that it can be performed using typical pharmaceutical equipment, making it suitable for scale-up and forming the basis for several advanced phytosome manufacturing strategies.
Rotary Evaporation / Thin-Film Formation Technique
Rotary evaporation is an improvised version of the solvent evaporation method in which continuous rotation under reduced pressure forms a uniform, thin lipid film. It reduces thermal degradation of heat-sensitive phytoconstituents (Prema et al., 2024). This technique is a further development of the solvent evaporation method, yielding a more homogeneous distribution of phytoconstituents and phospholipids, thereby increasing the reproducibility of complex formation. For instance, the quercetin phytosomes produced by rotary evaporation had a particle size of ~204.6 nm, entrapment efficiency of 84.48-88.59%, and a zeta potential of -28.6 mV (Kamireddy et al., 2025). In a similar way, the polyherbal formulation of milk thistle, curcumin and Ginkgo biloba extracts formed stable complexes with a zeta potential of -29.6 mV (Prema et al., 2024). The results show that rotary evaporation is one of the most commonly used methods for developing phytosomal systems that provide reproducible, controlled physicochemical properties.
Thin-Film Hydration Method
The thin-film hydration is an extension of the thin-film formation method, in which the dry lipid film is converted into vesicular phytosomal dispersions by adding a hydration step (Raouf et al., 2024). When the film is hydrated in an aqueous medium, multilamellar vesicles form, which can be reduced in size by homogenisation or sonication. For instance, the particle size of tetrahydrocurcumin phytosomes prepared in this manner was 317.35±5.48 nm, and the zeta potential was -29.88±0.35 mV, which confirmed the successful formation of vesicles (Raouf et al., 2024). Moreover, the particle size of hinokitiol-loaded phytosomes was reduced to 138.4 nm, and the entrapment efficiency was increased to 92.77% by the process of homogenisation (Ahmed et al., 2024). The results indicate the versatility of thin-film hydration as a method for preparing stable phytosomal vesicles.
Anti-Solvent Precipitation Method
In anti-solvent precipitation, a non-film-based method, the formation of phyto-phospholipid complexes is promoted by controlled precipitation from solution (Direito et al., 2025). The process is relatively simple and does not require the formation of a thin film, and can be processed efficiently. For example, the entrapment efficiency of Tinospora cordifolia phytosomes prepared by the anti-solvent precipitation method was 95.91%, and the formulation yield was approximately 80% (Peeriga et al., 2025). Similarly, polyherbal phytosomes containing extracts of Acalypha indica, Pergularia daemia, and Coleus amboinicus produced 158-nm nanoparticles with an entrapment efficiency of 86.94% (Vijayakumar et al., 2025). The results show the applicability of the anti-solvent precipitation method for obtaining highly entrapped phytosomal systems.
Co-Solvency Technique
The co-solvency technique was developed to overcome differences in the solubility of phytoconstituents and phospholipids by employing mixed-solvent systems that facilitate efficient molecular interactions prior to drying (Mankan et al., 2025). This approach is particularly useful for complex herbal extracts and thermolabile bioactives. For example, curcumin-lecithin complexes prepared using an ethanol-water co-solvent system followed by spray drying achieved entrapment efficiencies of 86.50-93.97% (Mankan et al., 2025). Similarly, α-mangostin-Phospholipon® 90G phytosomes, prepared using a chloroform-methanol system followed by lyophilisation, yielded nanoparticles of 138.9 nm with an entrapment efficiency of 95.10% and a zeta potential of -44.5 mV (Alamoudi et al., 2024). Collectively, these findings underscore the versatility of the co-solvency approach for producing phytosomal formulations with high entrapment efficiency and favourable physicochemical characteristics.
Mechanical Dispersion and Emulsification Approach
Mechanical dispersion and emulsification are particularly suitable for phytoconstituents with limited lipophilicity, in which phospholipids dissolved in an organic phase are brought into contact with an aqueous phase containing the phytoconstituent via agitation, emulsification, or ultrasonication to facilitate complex formation. Using this approach, Pentaclethra macrophylla seed extract phytosomes achieved entrapment efficiencies of up to 93% (Ugwu et al., 2025). Similarly, Callistemon citrinus extract phytosomes prepared by emulsification followed by ultrasonication produced nanoparticles of approximately 130 nm with entrapment efficiencies exceeding 80% (Magaña-Rodríguez et al., 2025). These results demonstrate the potential of mechanical dispersion to incorporate relatively hydrophilic phytoconstituents into formulations with desirable characteristics.
Comparative Overview of Preparation Methods
These preparation methods collectively offer adaptable strategies for customising phytosomal systems to specific phytoconstituents and applications, each with unique benefits related to particle size, entrapment efficiency, stability, and manufacturability. Among them, solvent evaporation, including rotary evaporation, and anti-solvent precipitation are particularly suitable for industrial-scale production due to their straightforward process, reproducibility, and compatibility with standard pharmaceutical equipment. The typical workflows for these methods are shown in Figure 3. Therefore, choosing the right preparation method should depend on the physicochemical properties of the phytoconstituent, desired formulation characteristics, scalability, and process requirements to ensure optimal phytosomal performance.
CHARACTERISATION
Particle Size, Polydispersity Index and Zeta Potential
The particle size, Polydispersity Index (PDI), and zeta potential are the key quality attributes which affect the stability, uniformity, and biological activity of phytosomal systems. Dynamic Light Scattering (DLS) and Electrophoretic Light Scattering (ELS) are widely used methods for determining these parameters (Maguire et al., 2018). These are greatly influenced by the phytoconstituent, phospholipid composition and the conditions of preparation. For instance, the particle size of Verbascoside phytosomes was 136.2 nm, with a PDI of 0.13, indicating high homogeneity (Cardullo et al., 2025). In the same manner, the phytosomes of Adiantum capillus-veneris exhibited a particle size of 187 nm, PDI of 0.2421 and a zeta potential of -17.22 mV. By contrast, the Aprepitant phytosomal emulsions exhibited a smaller particle size and a lower zeta potential (-59.0±2.54 mV), indicating better colloidal stability (Jagtap et al., 2023). All the above parameters provide significant evidence of the formation of stable, uniformly dispersed phytosomal systems (Németh et al., 2022).
Entrapment Efficiency
One important parameter indicating the formation of phytosomes is Entrapment Efficiency (EE). It indicates the degree of incorporation of the phytoconstituents into the phospholipid matrix. It is usually calculated by isolating the free drug from the phytosomal fraction and then quantitatively analysing it (Suwanpitak et al., 2024). Phytosomes have high EE values due to high intermolecular interactions. For instance, Vitexin phytosomes were prepared using soybean and egg phosphatidylcholine, which resulted in entrapment efficiencies of more than 98% (Peanparkdee & Yooying, 2023). Adiantum capillus-veneris, Sonneratia alba, and Bergamot essential oil phytosomes, on the contrary, showed EE values of 97-98.4%, 82.40%, and 87.89±4.14%, respectively (Albash et al., 2023; Dewi et al., 2024; Jagtap et al., 2023). The results show efficient phytoconstituent-phospholipid complexation.
Morphological and Structural Characterisation
Parameter | Phytosome | Liposome | Transferosomes | Ethosomes | Niosomes | SLNs | NLCs | Micelles |
|---|---|---|---|---|---|---|---|---|
Structure | Drug-phospholipid complex | Bilayer vesicle | Ultra-deformable vesicle | Ethanol-rich vesicle | Surfactant bilayer vesicle | Solid lipid matrix | Solid + liquid lipid matrix | Core-shell aggregate |
Components | Phospholipid+ phytoconstituent | Phospholipid + cholesterol | Phospholipid + edge activator | Phospholipid + ethanol | Surfactant + cholesterol | Solid lipids | Solid + liquid lipids | Amphiphilic surfactants |
Drug Loading Mechanism | Complexation | Encapsulation | Encapsulation | Encapsulation | Encapsulation | Matrix entrapment | Matrix entrapment | Core solubilisation |
Physical Stability | High | Moderate | Moderate | Good | Good | Moderate | High | Moderate |
Drug Leakage | Low | High | Moderate-High | Moderate | Low | Moderate | Low | Moderate |
Drug Loading Capacity | High | Moderate | Moderate-High | Moderate-High | High | Moderate | High | Moderate-High |
Scalability | Moderate | Moderate | Moderate | Moderate | High | High | High | High |
Advantage | Enhances phytoconstituent bioavailability | Suitable for hydrophilic & lipophilic drugs | Superior skin penetration | Enhanced transdermal delivery | Good stability | Improves oral delivery | High loading & stability | Excellent solubilisation |
Limitation | Limited commercialisation | Leakage & instability | Storage instability | Ethanol-related instability | Limited hydrophilic loading | Drug expulsion on storage | Complex formulation | Dissociation below CMC |
Abbreviations: SLN, solid lipid nanoparticle; NLC, nanostructured lipid carrier; CMC, critical micelle concentration.
Sl. No. | Product (Company) | Active Phytoconstituent | Therapeutic Application | Dose(mg/day) | Major Marketed Regions |
|---|---|---|---|---|---|
1. | Siliphos® (Indena, Italy) | Silybin ≥29.7-36.3% | Hepatoprotection and antioxidant support | 160-480 | USA, Canada, EU, Australia |
2. | Greenselect® Phytosome® (Indena, Italy) | Catechins ≥19-25%, EGCG ≥13% | Weight management and metabolic support | 300 | Italy, EU, USA, Canada, Australia, Japan |
3. | Leucoselect® Phytosome® (Indena, Italy) | OPCs >25-30% | Cardiovascular and vascular health | 300 | USA, Canada, EU, Australia |
4. | Ginkgoselect® Phytosome® (Indena, Italy) | Ginkgoflavonglucosides ≥7% + terpene lactones ≥2% | Cognitive and circulatory support | 120-360 | USA, Canada, EU, Australia, Japan |
5. | Meriva® (Indena, Italy) | Curcuminoids ≥18-22% | Anti-inflammatory, joint and metabolic health | 500-2000 | USA, Canada, EU, Australia, India, Japan |
6. | Quercefit® (Indena, Italy) | Quercetin ≥34-42% | Immune and respiratory support | 250-500 | USA, Canada, EU, Australia |
7. | Berbevis® (Indena, Italy) | Berberine ≥28-34% | Blood glucose and lipid management | 300-500 | USA, EU |
8. | Ubiqsome® (Indena, Italy) | Coenzyme Q10 ≥18-22% | Healthy ageing and cardiovascular support | 100-200 | USA, Canada, EU, Australia |
9. | Vazguard® (Indena, Italy) | Bergamot flavanols ≥14-18% | Lipid management and cardiovascular health | 500-1000 | USA, EU |
10. | Relissa™ (Indena, Italy) | Rosmarinic acid ≥17-23% | Sleep quality and mood support | 200-400 | USA, EU |
11. | Cronilief™ (Indena, Italy) | Palmitoylethanolamide | Inflammatory response support | 300-600 | USA, EU |
12. | Green Coffee Phytosome® (Indena, Italy) | Chlorogenic acids | Weight management and metabolic syndrome | 400 | USA, EU |
13. | Saw Palmetto Phytosome® (Indena, Italy) | Fatty acids ≥85% + β-sitosterol | Prostate health | 320 | USA, Canada, EU |
14. | Rhodiola Phytosome® (Indena, Italy) | Rosavins ≥3% + salidroside ≥1% | Adaptogen and stress reduction | 200-400 | EU, USA, Canada, Japan |
15. | Ginselect® (Indena, Italy) | Ginsenosides | Energy and immune support | 200-400 | EU, USA, Canada, Korea, Japan |
16. | AprésFlex® (Laila Nutraceuticals, India) | Boswellia serrata extract (20% AKBA) | Joint health and osteoarthritis | 100 | USA, Canada, EU, India |
17. | BioPerPhytosome® (Bioreal Technologies, India) | Curcuminoids | Anti-inflammatory and joint health | 500-1000 | India, EU, USA |
18. | Terminalia arjuna Phytosome® (Arjuna Natural, India) | Arjunolic acid + tannins | Cardiovascular support | 250-500 | India, EU, USA |
19. | Ashwagandha Phytosome® (Arjuna Natural, India) | Withanolides ≥5% | Adaptogen and cognitive support | 300-600 | India, USA, EU |
Dosage ranges represent commonly marketed or clinically investigated daily doses. They may vary according to product formulation and regional regulatory recom-mendations. Percentages indicate the standardised content of the principal active phytoconstituents. Proprietary products are identified by their respective manufactur-ers. In contrast, products without a specified company represent generic phytosomal formulations marketed by multiple nutraceutical brands. Abbreviations: EGCG, epigallocatechin gallate; OPCs, oligomeric proanthocyanidins; AKBA, acetyl-11-keto-β-boswellic acid; EU, European Union.
gives direct evidence of the formation of phytosomes. It differentiates between the real phytosome, the phyto-phospholipid complex, and a simple physical mixture. Most phytosomal formulations have a spherical, uniformly dispersed vesicular organisation. They are evaluated using microscopic methods such as SEM, TEM, FESEM, and AFM (Aziz et al., 2025). For example, the phytosomes of Pongamia pinnata exhibited spherical particles with good dispersion (Kapse et al., 2025), and the spray-dried curcumin phytosomes exhibited characteristic core-shell morphology (Mankan et al., 2025). FTIR, DSC, XRD and NMR analyses are also used to confirm the structural integrity. FTIR studies of aprepitant phytosomes showed hydrogen-bond interactions that were not chemically modified (Li et al., 2023). However, DSC and XRD analysis showed that the crystallinity of carvacrol and quercetin phytosomes was decreased, respectively (Kamireddy et al., 2025; Tafish et al., 2023). All these results collectively support the formation of stable supramolecular complexes with organised nanostructures rather than a simple physical mixture of phytosomal complexes.
Stability
assessment is important to ensure that the physicochemical properties and therapeutic activity are maintained throughout the storage period. Parameters monitored under ICH-recommended conditions are particle size, zeta potential, entrapment efficiency, and visual appearance. For instance, the zeta potentials of Cyclopia subternata phytosomes ranged from -55.0 to -38.9 mV. They offered enhanced protection to the phenolic constituents (Human et al., 2023). Similarly, the stability of Verbascoside phytosomes and Sonneratia alba phytosomes was found to be superior to a regular formulation (Cardullo et al., 2025) (Dewi et al., 2024). Spray-dried curcumin phytosomes, on the other hand, showed better thermal and digestive stability (Mankan et al., 2025). All of these results collectively suggest that phospholipid complexation helps prevent phytoconstituent degradation and maintains the stability of the formulation.
BIOPHARMACEUTICAL ADVANTAGES
After physicochemical characterisation, the importance of phytosomal systems lies in enhancing the in vivo performance of phytoconstituents. Phytosomes can be formulated as lipid-compatible molecular complexes, thereby improving membrane affinity and enhancing intestinal absorption, increasing systemic exposure and partly bypassing first-pass metabolism (Thakur et al., 2021). Besides, phospholipid complexation helps prevent chemical and enzymatic degradation of labile phytoconstituents, thereby enhancing bioavailability and circulation time (Lu et al., 2019). Several studies have demonstrated such advantages; for instance, Apigenin phytosomes exhibited enhanced oral bioavailability and antioxidant activity compared with free Apigenin (Telange et al., 2017). Silymarin phytosomes, on the other hand, demonstrated higher systemic exposure and better hepatoprotective efficacy compared with the conventional formulation (Shriram et al., 2022). Similarly, human pharmacokinetic evaluation of Quercetin Phytosome® showed significant increases in Cmax and AUC compared with unformulated quercetin, suggesting improved absorption and systemic availability (Riva et al., 2018). These pharmacokinetic parameters and bioavailability collectively explain the biopharmaceutical benefits of phytosome technology and form a solid foundation for the successful translation of the technology into clinically and commercially relevant phytopharmaceutical products.
Manufacturing And Regulatory Challenges
Although the biopharmaceutical benefits of Phytosome systems are impressive, translating these systems from the lab to commercial products is difficult. When scaling up to large-scale manufacturing, batch-to-batch consistency must be maintained, as botanical extract, phospholipid quality, and processing conditions can significantly impact critical quality attributes such as particle size, entrapment efficiency, and stability (Barani et al., 2021). To overcome these problems, the QbD and DoE approaches have been increasingly used to develop robust and reproducible manufacturing processes (Dewi et al., 2024). Furthermore, issues related to solvent use, residual toxicity, and ecological impact have prompted the adoption of more environmentally friendly solvents, such as ethanol, in large-scale production for sustainability (Kapse & Mulla, 2024).
In addition to manufacturing issues, other factors, such as regulatory restrictions, make the commercialisation of phytosomal formulations difficult. However, product approval and access to the global market are complicated by the lack of harmonised regulatory frameworks, variability in botanical materials, and the need for extensive quality, stability, toxicological, and pharmacokinetic evaluations (Kumbhar et al., 2025; Poudyal et al., 2022). In addition, there is still a lack of large-scale clinical evidence to support regulatory acceptance and widespread clinical adoption (Sakure et al., 2024).
However, manufacturing complexities and regulatory uncertainty are major translation barriers (Figure 4) that impede the successful commercialisation of many Phytosome products, despite their therapeutic potential.
Commercially Available Products
While the challenges of manufacturing and regulation remain, the success of several products shows that phytosomal formulations can help to close the gap between laboratory research and commercial application. Since Indena's advent of phytosome technology in 1989, many formulations have been developed for the treatment of hepatic, cardiovascular, metabolic, cognitive, and immune disorders. An overview of these products is presented in Table 2. The first success was with Siliphos®, a silybin-phosphatidylcholine complex, which proved to be more readily absorbed than conventional silymarin preparations (Sachdeva et al., 2024). This was followed by the introduction of Meriva®, Greenselect® Phytosome, Ginkgoselect® Phytosome, and Leucoselect® Phytosome, which further expanded the therapeutic applications of phytosome technology and generated growing clinical evidence of its efficacy (Chettupalli et al., 2025). In more recent times, phytosomal formulations have been used in sports nutrition, in healthy ageing and cosmeceuticals (Poudyal et al., 2022). As these products have become more commercially successful, significant innovation has occurred, with many patents filed for novel formulations and methods for producing phytosols. (Chen et al., 2024)
Sl. No. | Patent ID | Year | Title | Novelty | Country | Patent Status | Reference |
|---|---|---|---|---|---|---|---|
1. | WO-2023173104-A1 | 2023 | Phospholipid-containing discs and methods of manufacture | Dissolvable phospholipid-containing sheets/discs made by a specific high-viscosity casting and low-moisture drying process, enabling stable, high-load delivery of active ingredients. | International | PCT International Application | (Phipps et al., 2023) |
2. | DE-202023102351-U1 | 2023 | Phospholipid-based nanovesicles for improved delivery of boswellic acids | Phytosomal composition of Boswellia acids and phospholipids at a weight ratio of 1:1 to 1:4 (preferably 1:3.5), forming nano-vesicles that improve solubility and bioavailability for treating inflammatory conditions like arthritis. | Germany | Utility Model | (Bhole et al., 2023) |
3. | CN-116271082-A | 2023 | Polysaccharide-modified phospholipid complex and preparation method thereof | Polysaccharide-modified medicinal phospholipid complex in which a phospholipid-drug-drug-drug complex is further coated or conjugated with polysaccharide to enhance tumour targeting, aggregation in tumour cells, and antitumor therapeutic efficacy via synergistic and active-targeting effects. | China | Patent Application | (Chen, 2023) |
4. | RO-137953-A2 | 2024 | Phytosomes with biologically active compounds from ginger rhizomes and rosehips | Phytosomes formed from ginger and rosehip hydroalcoholic extracts with phosphatidylcholine at controlled mass ratios, using a defined reflux-sonication process to yield nanoemulsions with high loading efficiency and enhanced bioavailability. | Romania | Patent Application | (Deleanu et al., 2024) |
5. | CN-118903230-A | 2024 | Methyl jasmonate-induced phospholipid nanomaterial of Phellodendron amurense extract | Methyl jasmonate-inducedPhellodendron amurense adventitious root extract bonded with phospholipids to form a nanomaterial, enhancing stability, solubility, bioavailability, anti-inflammatory, and antitumor effects. | China | Patent Application | (Xu & Wang, 2024) |
6. | IT-202200020370-A1 | 2024 | Composition useful as an adjuvant in the treatment of acute and chronic pain | Composition combiningBoswellia serrata extract and coenzyme Q10 (optionally in phytosomal form) for use as an adjuvant in treating acute/chronic pain, especially musculoskeletal inflammation/ trauma in athletes, showing synergistic anti-inflammatory and recovery effects without bleeding risk. | Italy | Patent Application | (Davolio, 2024) |
7. | CN-117503946-A | 2024 | Preparation method of lignum naucleae extract phospholipid complex | Phospholipid complex ofZanthoxylum avicennae extract and phospholipids at mass ratio 1:1 to 1:5, prepared by solvent dissolution, stirring, and evaporation to boost oral bioavailability and mask bitterness for respiratory/inflammatory treatments. | China | Patent Application | (Chen et al., 2024) |
8. | CN-118697762-A | 2024 | Pharmaceutical composition of naringenin and polyethene glycol | Drug composition in which naringenin is present as a phospholipid complex (phospholipid: naringenin weight ratio 2-10:1) combined with 20-30% compound polyethene glycol and excipients, to enhance solubility, stability, and overall bioavailability of naringenin. | China | Patent Application | (Wang et al., 2024) |
9. | US-12472188-B1 | 2025 | Method and composition for an improved bioavailability delivery system | A multi-bioavailability delivery system in which a DHEA-derivative supplement is combined with multiple actives and processed as an encapsulated micronised phytosomal formulation | United States | Granted Patent | (Beri, 2025) |
10. | EP-4661696-A1 | 2025 | Nutraceutical composition based on Boswellia serrata gum resin | Nutraceutical composition of Boswellia serrata gum resin dry extract (50-90 wt%), stearic acid (4-45 wt%), and phosphatidylcholine source (1-5 wt%) to enhance bioavailability, with a defined preparation process. | Europe | EPO Patent Application | (Rossano et al., 2025) |
11. | KR-102881749-B1 | 2025 | Cosmetic composition with vesicles containing poorly soluble polyphenols and water-soluble extracts | Cosmetic composition containing niosomal / phytosomal vesicles that co-encapsulate water-insoluble polyphenols and water-soluble extracts fromMagnolia sieboldii, improving simultaneous delivery and stability of both hydrophobic and hydrophilic magnolia actives for skin applications. | Republic of Korea | Granted Patent | (Kim et al., 2025) |
12. | KR-102881748-B1 | 2025 | Method for manufacturing niosome-based phytosomal vesicles | Method for preparing niosomal, phytosome-like vesicles that efficiently encapsulate both poorly soluble polyphenols and water-soluble actives, enabling stable co-delivery of hydrophobic and hydrophilic ingredients in cosmetic compositions. | Republic of Korea | Granted Patent | (Kim et al., 2025) |
13. | KR-20250006756-A | 2025 | Powder composition containing Centella asiatica extract | Powder composition containing titrated extract of Centella asiatica formulated with specific carriers into a stable powder form, improving handling and enabling convenient incorporation into dermatological or cosmetic products for skin benefits. | Republic of Korea | Patent Application | (Jin et al., 2025) |
14. | WO-2025109630-A1 | 2025 | Water-soluble micellar formulation comprising curcumin and piperine | Water-soluble micellar formulation containing curcumin and piperine (weight ratio 20:1-50:1) with 77-82% non-ionic water-soluble surfactant and 13-18% cosurfactant, designed to markedly enhance solubility and bioavailability, and usable via multiple administration routes. | International | PCT International Application | (Waghode et al., 2025) |
Patent status refers to the state or jurisdiction of intellectual property protection. It includes national patent applications, granted patents, utility models, European Patent Office (EPO) applications, and Patent Cooperation Treaty (PCT) international applications. The novelty column summarises the principal technological innova-tions introduced by each patent. Abbreviations: PEG, polyethylene glycol; CoQ10, coenzyme Q10; SMEDDS, self-microemulsifying drug delivery system; PCT, Patent Cooperation Treaty; EPO, European Patent Office.
Patent Landscape
The growing market interest in phytosome technology has been accompanied by substantial intellectual property development, reflecting ongoing efforts to refine formulation design and broaden therapeutic applications. A summary of representative patents published from 2023 to 2025 is presented in Table 3. Recent innovations reveal a shift from conventional phytosome complexes toward more sophisticated phospholipid-based architectures, including nanovesicles, micelles, SMEDDS, and multifunctional hybrid systems to improve the solubility, stability, and bioavailability of poorly absorbed bioactives. Considerable attention has also been directed toward scalable manufacturing strategies and the development of solid phospholipid-based systems with enhanced stability and dissolution characteristics. Furthermore, emerging patents demonstrate the extension of phytosome technology beyond oral delivery to nutraceutical, dermatological, and cosmeceutical applications. Overall, current patent trends highlight the growing versatility of phospholipids as multifunctional components of advanced delivery platforms. However, limited in vivo and clinical validation remains a major challenge for the successful translation of next-generation phytosomal technologies.
CONCLUSION
Phytosome technology has come a long way from its original concept of enhancing oral bioavailability to its present state as a commercially proven, versatile drug delivery technology with a wide range of therapeutic applications. The phosphatidylcholine-phytoconstituent complex improves membrane permeability and lymphatic uptake, provides structural stability, reduces first-pass metabolism, and improves patient compliance, all of which help connect the dots between promising botanical pharmacology and clinically relevant results.
The commercial landscape remains highly consolidated, with Indena S.p.A.'s Phytosome® platform covering hepatoprotective (Siliphos®), anti-inflammatory (Meriva®), and cognitive (Ginkgoselect® Phytosome®) indications, implying that new market players will need botanicals or therapeutic areas. At the same time, the patent landscape shows a definite geographic shift, with Chinese and Korean filings joining established US and WO applications, and the list of actives being developed as phytosomal growing from classical flavonoids to oncology agents and cannabidiol and melatonin, pointing to a wider therapeutic spectrum that will lead the next generation of clinical and regulatory activity.
Although there is strong commercial precedent and a growing global patent estate, the lack of a standardised in vitro-in vivo correlation model and regulatory guidance for phytosomes is the major translational obstacle. There is a gap to be filled, and the ongoing integration of Quality by Design into manufacturing is a challenge for academia and industry to work together. Overall, phytosome technology is a fascinating blend of ancient and contemporary science, with the potential to shape the future of botanical medicine and pharmaceuticals.
ACKNOWLEDGEMENT
We acknowledge the support from the NGSM Institute of Pharmaceutical Sciences, Nitte (Deemed to be University), Mangalore, Karnataka, for providing library access, infrastructure and other necessary resources to complete this work.
1,2-Dioleoyl-sn-Glycero-3-Phosphocholine; 1,2-Dipalmitoyl-Sn-Glycero-3-Phosphocholine; 1,2-Distearoyl-sn-Glycero-3-Phosphoethanolamine; hydrogenated soy phosphatidylcholine; SEM: Scanning Electron Microscopy; TEM: Transmission Electron Microscopy; FESEM: Field Emission Scanning Electron Microscopy; AFM: Atomic Force Microscopy; FTIR: Fourier Transform Infrared Spectroscopy; DSC: Differential Scanning Calorimetry; XRD: X-ray Diffraction; NMR: Nuclear Magnetic Resonance; ICH: International Council for Harmonisation; Cmax: Maximum Plasma Concentration; AUC: Area Under the Concentration-Time Curve; QbD: Quality by Design; DoE: Design of Experiments.
