B. R. Harne college of Pharmacy.
Herbal medicines have long played a crucial role in healthcare system, yet their clinical use restricted due to poor solubility, low absorption, instability and rapid metabolism. To analyse these drawbacks, novel drug delivery systems (NDDS) have arisen as an advanced approach for improving the therapeutic efficiency of phytoconstituents. This review focuses on the necessity of NDDS in herbal formulations by highlighting the physicochemical and biological properties of conventional herbal preparations. Various carrier-based delivery systems such as liposomes, ethosomes, phytosomes, niosomes, microspheres and microemulsions are discussed in detail, emphasizing their role in enhancing stability, bioavailability, site-specific delivery and controlled release of active herbal components. In addition, the article outlines the current challenges faced in upgrading and modernizing herbal formulations, including issues of standardization, scale-up, regulatory acceptance and patient compliance. Analytical aspects of novel herbal formulations are also explained, covering the essential evaluation parameters such as particle size, surface charge, encapsulation efficiency and stability testing. Overall, this review underlines the potential of integrating traditional herbal knowledge with modern drug delivery technologies to develop safe, effective herbal medicaments.
Necessity of NDDS in Herbal Drugs
To ensure better patient compliance and to reduce the burden of recurrent administration, herbal medicines require advanced systems that can deliver therapeutic agents in a controlled and sustained manner. The development of Novel Drug Delivery Systems (NDDS) for phytotherapeutics offers a way to achieve this by improving bioavailability, enhancing stability and reducing toxicity, thereby minimizing repeated dosing.
Herbal medicines are widely accepted due to their low cost, accessibility, minimal side effects and effectiveness in managing chronic and lifestyle-related disorders. However, conventional formulations often faced poor solubility, instability and low absorption. Incorporating modern drug delivery technologies into herbal medicine can overcome these challenges, thereby improving efficacy and safety profiles of herbal formulations. (1)
NDDS can be designed either by incorporating herbal drugs into carrier systems or by modifying their structure to provide controlled, sustained and targeted delivery. This approach helps address the limitations of traditional dosage forms while enhancing therapeutic potential. In the context of Ayurveda and other traditional systems, integrating NDDS can significantly strengthen the role of herbal medicines in combating serious diseases. Targeted carriers release the active constituents at a specific site and at a predetermined rate, thereby enhancing bioavailability while reducing systemic side effects.
Physiochemical and biological properties of herbal drugs (2)
Physiochemical properties of herbal drugs:
Biological properties of herbal drugs:
Selection of Herbal Drug and Novel Drug Delivery System:
In selecting an herbal drug and a novel drug delivery system (NDDS), it's important to consider the therapeutic properties of the herb and how drug delivery system can enhance its efficacy. Here's a general guideline on how to approach both selections: (3)
1. Selection of Herbal Drug:
Therapeutic Properties: Choose an herb with proven pharmacological effects related to the desired treatment (e.g., Celosia argentea for kidney stones).
Active Constituents: Identify the key active compounds responsible for the medicinal effects, such as flavonoids, alkaloids or terpenoids.
Toxicity and Safety: The herb should have a well-documented safety profile with minimal side effects.
Sustainability and Availability: Consider the availability and sustainability of sourcing the herb.
2. Selection of Novel Drug Delivery System (NDDS):
NDDS enhances the delivery of active ingredients of herbal drugs, improving their bioavailability, controlled release and targeted action.
Nanoparticles: This can protect the active components from degradation and enhance absorption in the body. For example, encapsulating Celosia argentea extracts in nanoparticles may enhance its therapeutic potential for kidney stones.
Liposomes: Liposomes can increase the solubility and bioavailability of herbal drugs, making them a good option for poorly soluble phytochemicals.
Phytosomes: These are herbal extracts bound to phospholipids to enhance their bioavailability and often used for polyphenols and flavonoids.
Advantages of NHDDS (4)
Disadvantages of NHDDS (5)
Current Challenges in Upgrading and Modernization of Herbal Formulations (6)
The modernization of herbal formulations faced several challenges due to the complex nature, variability and limited scientific validation of herbal products.
1. Management within Ranges of Risk
Establishing safety margins for herbal medicines is difficult because of variations in plant sources, geographical conditions, cultivation methods and processing techniques. Toxicity profiles, dose optimization and long-term safety are not consistently defined.
2. Communication of Uncertainty
Many herbal formulations lack strong clinical evidence and uncertainties regarding their safety and efficacy persist. Communicating these uncertainties transparently to healthcare providers and patients is challenging.
3. Pharmacological, Toxicological, and Clinical Documentation
Limited well-structured studies exist on the pharmacology, toxicity and clinical efficacy of herbal drugs.
4. Pharmacovigilance (7)
The absence of robust post-marketing surveillance systems for herbal drugs delays the detection and reporting of adverse reactions. Underreporting and poorly understood herb–drug interactions further complicate pharmacovigilance in herbal medicine.
5. Role of Harmful Additives
In certain traditional formulations, harmful additives such as heavy metals or toxic substances have been historically used. Understanding their role and finding safer alternatives without compromising efficacy remains a key challenge for modernization.
Approaches in novel herbal drug delivery system
1. Liposome
Liposomes are vesicular carriers that may consist of a single, few or multiple concentric phospholipid bilayers surrounding an aqueous core. The hydrophilic nature of the central compartment allows the encapsulation of polar drug molecules, while lipophilic and amphiphilic compounds can be incorporated within the lipid bilayer depending on their affinity for phospholipids. This dual structural organization provides liposomes with the unique ability to entrap both hydrophilic and hydrophobic agents simultaneously. (8)
Fig 1. Structure of liposome
Methods of preparation: (9)
1) Thin film hydration technique
2) Micro emulsification
3) Ether injection method
4) Ethanol injection method
Advantages of liposome formulation:
?Hydrophobic and hydrophilic drugs can be delivered.
? Liposome herbal therapy acts as a carrier for small cytotoxic molecules and as a vehicle for macromolecules as genes.
? Sustained and controlled release of formulation can be possible.
Disadvantages of liposome preparation:
? Low solubility
? Leakage and fusion of encapsulated drug/molecules
? Production cost is high
? Fewer stables
? Sometimes phospholipids undergo oxidation and hydrolysis-like reaction.
? Short half-life.
2. Phytosomes
Phytosomes are molecular complexes formed by the interaction of a stoichiometric amount of phospholipid, typically phosphatidylcholine, with standardized plant extracts or polyphenolic constituents such as flavonoids in a nonpolar solvent. Phosphatidylcholine is amphiphilic in nature, consisting of a hydrophilic choline head group and a lipophilic phosphatidyl tail. The polar choline moiety forms hydrogen bonds with phytoconstituents, while the hydrophobic portion surrounds the complex, resulting in a stable lipid-compatible phyto-phospholipid complex. (10)
Fig 2. Structure of phytosome
Methods of phytosome preparation: (11)
1) Solvent Injection Method
2) Solvent Evaporation Method
3) Anti-Solvent Precipitation Method
4) Mechanical Dispersion Method
Advantages on phytosome formulation:
? Increased bioavailability due to phospholipid complex.
? Improved absorption in GIT.
? Increased bioavailability causes improved therapeutic effect.
? Less dose requirement due to high bioavailability.
? Higher stability.
? High lipophilicity causes high penetrability, henceforth used in cosmetics over liposomes
Disadvantages of phytosome formulation:
? Phytoconstituents is quickly eliminated from phytosomes.
? phospholipids (lecithin) can provoke the proliferation on MCF-7 breast cancer cell line
? Phytosomes could rapidly eliminate the phytoconstituents
3. Niosome
Niosomes are non-ionic surfactant-based vesicular systems that structurally resemble liposomes but differ in composition and stability. They are typically prepared using non-ionic surfactants along with cholesterol, although other additives may also be incorporated to modulate their properties. Niosomes consist of a bilayer similar to liposomes; however, due to the use of synthetic surfactants, they exhibit greater chemical stability and longer shelf life. Their small particle size, usually in the nanometric range of 10–100 nm, facilitates deeper penetration and improved bioavailability compared to conventional emulsion formulations. (12)
Fig 3. Structure of niosome
Methods of preparation:
Advantages of niosomal formulations: (13)
? They are osmotically active and stable.
? They increase the stability of the entrapped drug
? Handling and storage of surfactants do not require any special conditions
? Can increase the oral bioavailability of drugs
? Can enhance the skin penetration of drugs
? They can be used for oral, parenteral as well as topical.
Disadvantages of niosomal formulations:
? Physical instability
? Aggregation
? Fusion
? Leaking of entrapped drug
? Hydrolysis of encapsulated drugs which limiting the shelf life of the dispersion.
4. Ethosomes
Ethosomes are soft, flexible lipid vesicles composed of phospholipids, water,and relatively high concentrations of alcohol (20–45%), typically ethanol or isopropyl alcohol. First introduced by Touitou and colleagues in 1997, ethosomes are recognized for their remarkable deformability, which enables them to penetrate the skin intact and deliver therapeutic agents effectively through the transdermal route. The vesicle-forming component of ethosomes is primarily phospholipids, which are incorporated in concentrations ranging from 0.5–10%. (14)
Fig 4. Structure of ethosome
Methods of preparation:
? Cold Method
? Hot Method
? Classic mechanical dispersion method
Advantages of ethosomes formulation: (15)
? Enhanced permeation of drug through skin for Transdermal drug delivery.
? Delivery of large molecules (peptides, protein molecules) is possible
? It contains nontoxic raw material in Formulation.
? High patient compliance the ethosomal drug Is administered in semisolid form (gel or Cream) hence producing high patient Compliance.
Disadvantages of ethosomes formulations:
? Poor yield.
? In case if shell locking is ineffective then the ethosomes may coalesce.
? Might not be economical.
? Loss of product during transfer from organic to water media.
5. Microspheres
Microspheres are small, spherical particles with diameters typically ranging from 1 to 1000 µm. They are also referred to as microparticles and can be synthesized from a wide variety of natural and synthetic materials. Depending on their composition, microspheres may be solid or hollow and can exhibit diverse densities, which makes them suitable for numerous biomedical and pharmaceutical applications. Commonly available microspheres include glass, polymeric and ceramic types. (16)
Fig 5. Structure of microsphere
Methods of preparation:
? Spray Drying
? Solvent Evaporation
? Single emulsion technique
? Phase separation coacervation technique.
? Spray drying and spray congealing.
? Solvent extraction.
Advantages of microspheres:
? Microspheres provide constant and prolonged Therapeutic effects.
? Reduces the dosing frequency and thereby improves patient compliance.
? They could be injected into the body due to the Spherical shape and smaller size.
? Better drug utilization will improve the bioavailability and reduce the incidence or intensity of adverse effects. (17)
Disadvantages of microspheres:
? The modified release from the formulations.
? The release rate of the controlled release dosage form may vary from a variety of factors like food and the rate of transit through the gut.
? Differences in the release rate from one dose to another.
6. Microemulsion
Microemulsions are thermodynamically stable, isotropic mixtures of oil, water, surfactant, and often a co-surfactant. When surfactants with a balanced hydrophilic–lipophilic nature are employed at appropriate concentrations, they form a unique oil–water system that differs significantly from conventional emulsions such as milk. Unlike coarse emulsions, microemulsions are transparent or translucent, with droplet sizes typically ranging between 10 and 100 nm. (18)
Fig 6. Structure of microemulsion
Advantages of microemulsion:
? Microemulsions are ready and require no energy during preparation due to the improvement of thermodynamics stability.
? The thermodynamically stable system of microemulsions allow the system to self-emulsify.
? Compared to emulsions, microemulsions have low viscosity.
? The capacity to take lipophilic and hydrophilic medicinal products.
Disadvantages of microemulsion systems:
? Having limited solubilizing capacity for high- melting substances.
? Require a large number of Surfactants for stabilizing droplets.
? Microemulsion stability is influenced by environmental parameters such as temperature and PH.
Analytical Aspects of Novel Herbal Formulations (19)
1. Visualization – Structural morphology of vesicular systems such as phytosomes, liposomes, and niosomes can be visualized using transmission electron microscopy (TEM) and scanning electron microscopy (SEM).
2. Particle Size and Zeta Potential – Dynamic light scattering (DLS) and photon correlation spectroscopy are commonly used to determine the average particle size and surface charge, which influence stability and bioavailability.
3. Entrapment Efficiency – The percentage of drug encapsulated within the carrier can be evaluated using ultracentrifugation techniques.
4. Transition Temperature – Differential scanning calorimetry (DSC) provides insights into the thermotropic behavior of lipid bilayers and vesicular stability.
5. Surface Tension – Surface activity of drug molecules in aqueous solution can be studied using a Du Nouy ring tensiometer.
6. Vehicle Stability – Vesicular integrity and mean particle size are monitored over time by DLS, while morphological changes are examined by TEM.
7. Drug Content – Quantification of the active phytoconstituents can be carried out using high-performance liquid chromatography (HPLC) or appropriate spectroscopic methods.
8. In Vitro Drug Release – Dissolution studies using USP Type II (paddle) apparatus assess drug release kinetics, with samples analyzed by UV–visible spectrophotometry.
9. Excipient Compatibility – Fourier Transform Infrared Spectroscopy (FTIR) is used to detect potential chemical interactions between plant extracts and excipients.
10. Spectroscopic and Chromatographic Analysis – Advanced tools such as ^1H-NMR, UV, and chromatographic profiling help confirm the formation of phytoconstituent–phospholipid complexes and provide molecular interaction insights.
CONCLUSION
Several therapeutic potentials are there in plant-based substances or herbal medications, which should be examined using cutting-edge drug delivery technology. This study provides information on the varieties, formulations, applications, and innovative drug delivery systems of herbal medicines as well as on the state of the market at the time of writing. Yet, in order to promote patient compliance and prevent recurrent administration, phytotherapeutics require a scientific methodology to provide the components in a novel way. Designing NDDS for natural compounds can do this. For the delivery of herbal drugs, two businesses, Cosmetochem and Indena, introduce liposomes and phytosomes preparations with a range of therapeutic advantages. Compared to their synthetic cousin, herbal excipients are less costly, easily accessible, and non-toxic. In order to have better materials for drug delivery systems, there will continue to be interest in natural excipients in the near future. There are several obstacles to updating and modernising the delivery system for herbal drugs, including the destruction of forests, a lack of scientific validation and standardisation, a lack of quality and regulatory considerations, and a lack of pharmacokinetic investigations of bioactive compounds. Although there are many different phytosome products on the market, many more phytoconstituents that have a great potential to heal serious illnesses have not been included into phytosome technology. To create phytosomes that are very target-specific, more research may be done.
REFERENCES
Alpesh Dalvi*, Preeti Chauhan, Novel Herbal Drug Delivery Systems: Advancing Phytotherapy through Modern Formulation Approaches, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 11, 565-574 https://doi.org/10.5281/zenodo.17528597
10.5281/zenodo.17528597
