Herbal-Synthetic Drug Combinations in Emulgels: A Novel Approach for Enhanced Topical Therapy

Abstract

Combining herbal and synthetic drugs into emulgel formulations offers a novel and effective approach for topical drug delivery, merging the therapeutic benefits of natural bioactives with the potency of synthetic compounds. Emulgels provide enhanced drug penetration, controlled release, and improved patient compliance due to their unique emulsion-in-gel structure. This review discusses the formulation aspects, rationale, and advantages of integrating herbal and synthetic drugs in emulgels, along with challenges such as compatibility issues, stability concerns, standardization of herbal extracts, and regulatory hurdles. Marketed formulations and recent patents highlight the growing interest and innovation in this field. Future perspectives emphasize advancements in nanotechnology, personalized therapy, and sustainable formulations. Overall, herbal-synthetic emulgels represent a promising direction for developing multi-functional, safe, and effective topical therapies with broad therapeutic applications.

Keywords

Introduction

Figure No.01: Emulgel in Topical Drug Delivery.(7)

Figure No.02: Delivery of Emulgel in layers of skin.(9)

Herbal drugs used in emulgel formulation:

• Common herbal extracts used in emulgel –

1. Curcumin (from Curcuma longa)

The common name of curcumin is Haldi or Turmeric. It belongs to the family Zingiberaceae. Chemical constituents present in curcumin are Diarylheptanoids, curcumin, dimethoxy curcumin, and bisdemethoxycurcumin. It shows medicinal properties like Anti-inflammatory, antiulcer, and antiarthritic activity.(10)

2. Menthol (from Mentha piperita)

By interacting with sensory nerve endings, especially cold receptors, menthol cools the skin and mucosal surfaces. It encourages the skin to receive more blood flow. Improves other medications skin absorption. Most people agree that menthol is not sensitizing.(11)

3. Clove oil (from Syzygium aromaticum)

For many years, eugenol (2-methoxy-4-(2-propenyl) phenol, the main chemical component of clove oil (Eugenia aromatica), has been utilized as an analgesic in dentistry. In more recent times, eugenol's pharmacological qualities have been shown to include anti-inflammatory, anti-bacterial, anesthetic, and neuroprotective actions.(12)

4. Basil Oil / Tulsi Oil (from Ocimum basilicum)

The most common species of the genus, Ocimum tenuiflorum L. (Lamiaceae), is grown for its therapeutic properties all over the world. Anti-inflammatory, antibacterial, antistress, anticancer, immunomodulatory, radiation protection, wound healing, antidiabetic, and antioxidant properties of Os have been documented.(13)

Benefits of Herbal emulgel formulation –

1. Better Drug Administration for Herbal Extracts That are Hydrophobic: It is challenging to distribute several herbal components (such as curcumin, clove oil, and basil oil) efficiently in traditional gels or creams because they are hydrophobic and have low solubility and permeability.

2. Better Intake and Penetration: By use of dual-phase emulsification, emulgels facilitate deeper penetration of the skin or mucosa. Herbal actives diffuse more readily into the skin or mucosa when penetration enhancers like menthol and clove oil are used.

3. Benefits to the senses and appearance: Emulgels are patient-friendly and cosmetically acceptable due to their non-greasy, translucent, readily spreadable, and pleasant texture and scent. Ideal for areas of the skin with hair, where creams and ointments might not work as well.

4. Increased Shelf-Life and Stability: Emulgels are more physically stable than emulsions and creams, and there is a lower chance of phase separation or oil rancidity.

5. Polyherbal Combinations' Synergistic Effects: To achieve multi-targeted effects, such as combining anti-inflammatory and antibacterial compounds in a single formulation, many emulgels contain various herbal extracts.

6. Improved Adherence to Treatment: Topical emulgels improve user convenience and compliance by avoiding first-pass metabolism, providing non-invasive administration, and facilitating simple withdrawal.(4)

Challenges in Herbal Emulgel Formulations –

• Improved Adherence to Treatment: Topical emulgels improve user convenience and compliance by avoiding first-pass metabolism, providing non-invasive administration, and facilitating simple withdrawal.
• Problems with Stability: Degradation and temperature sensitivity are common characteristics of volatile oils, such as clove and basil oil. The usage of antioxidants and the right ratios of emulsifiers (Span 80 and Tween 80) are essential.
• Consistency & Homogeneity: Achieving a stable, homogeneous gel with adequate viscosity and spreadability is technically tough. Carbopol 940, used as a gelling agent, needs to be carefully tuned for rheological qualities.
• pH Compatibility: To prevent irritation of the mucosa, oral applications need a pH of 6.5 to 7.0. The pH was kept at 6.7 by optimized formulations.(14)

Synthetic Drugs in Emulgel Formulations:

Common synthetic drugs used in enulgels –

• Chlorphensin: Chlorphenesin (CHL), which possesses antibacterial and antifungal properties. It is administered topically to treat various cutaneous diseases, including moderate, simple dermatophytes.(15)
• Piroxicam: Piroxicam is a non-steroidal anti-inflammatory drug (NSAID) that possesses pain-relieving and fever-reducing properties. It is commonly used to treat conditions such as rheumatoid arthritis, osteoarthritis, and injuries resulting from trauma.(16)
• Mefenamic acid: Mefenamic acid, a potent NSAID, has traditionally been used for its anti-inflammatory and analgesic properties. It is commonly available in the form of tablets and suspensions.(17)
• hlotrimazole: Clotrimazole is an antifungal medication that prevents the growth of harmful dermatophytes. Alongside econazole and miconazole, it is considered a first-line option for the topical treatment of tinea pedis, tinea cruris, and tinea corporis caused by *Candida albicans*. It is also effective for treating vulvovaginal and oropharyngeal candidiasis when applied topically.(18)
• Ornidazole: Ornidazole is an antiprotozoal medication used to treat various protozoal infections affecting the stomach, intestines, genital area, and certain strains of anaerobic bacteria. It is also administered to help prevent potential infections during surgical procedures.(19)
• Other NSAID drugs like Diclofenac sodium, Ibuprofen, and Ketoprofen are used in the treatment of joint pain, arthritis, and inflammation. Antifungal agents like Ketoconazole, Miconazole are used in the management of superficial fungal infections. Anti-bacterial agents like Metronidazole, Mupirocin, and Ciprofloxacin are used in the treatment of skin infections like acne, cellulitis. Corticosteroids like Hydrocortisone, Betamethasone, and Mometasone are used in the management of eczema, psoriasis, and allergic reactions.

Advantages of Using Synthetic Drugs in Emulgels –

1. Bypasses Liver Metabolism: Applying drugs to the skin avoids the liver’s first-pass effect, leading to better absorption and more effective delivery.
2. Non-Invasive and Easy to Use: It eliminates the need for needles or swallowing pills, making it more comfortable and user-friendly for patients.
3. Targeted Treatment: Medications can be applied directly to the affected area, providing focused therapy with fewer systemic side effects.
4. Sustained Drug Release; Modern gel systems (like hydrogels and emulgels) can release drugs gradually, maintaining therapeutic levels over time.
5. Better Patient Acceptance: Gels often feel pleasant on the skin, are non-greasy, and are easy to apply and remove, enhancing patient satisfaction.
6. Improved Skin Penetration: Certain gel formulations contain ingredients that help the drug pass through the skin barrier more effectively.
7. Suitable for Various Drug Types: A wide range of active substances can be delivered through the skin using different gel bases—water-based for water-soluble drugs and oil-based for fat-soluble drugs.
8. Avoids Digestive Side Effects: Since the drug is not taken orally, it reduces the risk of stomach irritation and digestive discomfort.
9. Lower Risk of Systemic Effects: Topical application minimizes the amount of drug entering the bloodstream, lowering the chance of whole-body side effects.(20)

Formulation considerations –

Developing effective topical drug formulations involves several important considerations to ensure proper skin absorption, therapeutic action, and user safety. A key factor is the drug's physicochemical characteristics—such as its molecular weight, solubility, and ionization. Smaller drugs (under 500 Daltons) that have a balanced lipophilic and hydrophilic nature tend to penetrate the skin more efficiently. Maintaining the formulation's pH close to the skin's natural level (around 5.5) helps prevent irritation and supports better drug absorption by keeping the drug in its uncharged, more absorbable form. The choice of base, like creams, ointments, gels, or emulsions, and additional ingredients such as penetration enhancers can influence how well a drug is released and absorbed through the skin.

The skin’s outermost layer, the stratum corneum, serves as the main barrier to absorption. Increasing the hydration of this layer through occlusive formulations can enhance drug penetration. Skin temperature also affects absorption, with higher temperatures promoting increased drug movement. Advanced delivery systems such as nanoparticles, liposomes, and microemulsions can help transport a wider range of drugs and create reservoirs in the skin for prolonged drug release. Additionally, enzymes present in the skin can metabolize drugs, potentially affecting their effectiveness and safety. Once a drug penetrates the skin, it can be removed through blood vessels or the lymphatic system, influencing how long it stays active locally.

To evaluate how well a topical formulation works, several methods are used. Tape stripping measures drug concentration in the outer skin layers, while microdialysis tracks drug levels deeper in the skin over time.

Confocal microscopy offers visual insights into drug distribution, and vasoconstrictor assays are used to test the potency of corticosteroid products. Together, these considerations help in designing topical products that are both efficient and safe for users.(21)

Challenges and limitations –

1. Balancing Local and Systemic Effects

Although topical treatments intend to concentrate the drug at the target area with minimal absorption into the bloodstream, some medications may still enter systemic circulation, potentially leading to side effects

2. Skin Barrier Limitations

The outer skin layer (stratum corneum) serves as a major obstacle to drug penetration. Only certain types of molecules—those that are small and moderately fat-soluble—can easily pass through. Enhancing absorption without damaging the skin is a key challenge.

3. Formulation Durability

Topical products like ointments and gels must remain chemically and physically stable during storage. If components break down or separate, it can compromise drug release and effectiveness.

4. User Friendliness

Many topical products can be greasy, have an unpleasant smell, or stain clothing, which can discourage patients from using them consistently. A user-friendly design is essential for better adherence.

5. Inconsistent Absorption

Drug uptake can vary widely depending on the application site, individual skin characteristics, and environmental conditions. Factors such as skin thickness and hydration can significantly impact how much drug is absorbed.

6. Skin Reactions

Topical drugs may cause localized side effects like irritation, redness, or rashes. Formulas must be carefully designed to deliver the drug effectively while minimizing skin discomfort.

7. Assessing Drug Availability

For topical drugs not intended to enter the bloodstream, standard measures like blood concentration levels aren't useful, making it more difficult to evaluate how much of the drug is effectively delivered.(22)

Rationale for Combining Herbal and Synthetic Drugs:

• Synergistic Therapeutic Effects

The possibility of synergistic action is one of the main reasons for combining synthetic and natural medications. Some herbal active ingredients can improve the pharmacological action of synthetic medications when taken in combination, increasing their therapeutic efficacy compared to when taken separately. As an illustration, consider the anti-inflammatory synergy of curcumin (herbal) with diclofenac (synthetic). Herbal remedies may alter oxidative stress or inflammatory pathways to enhance the main effects of synthetic drugs.

• Dose Reduction and Side Effect Minimization

By improving the overall therapeutic impact, herbal medications may allow for a reduction in the dose of the synthetic drug necessary to obtain the same result. This can reduce systemic adverse effects, minimize the toxicity of drugs, and boost security, particularly for long-term topical application.

• Multifunctional Activity

Numerous biological activities, including anti-inflammatory, antioxidant, antibacterial, and wound-healing properties, are frequently seen in herbal medications. The outcome is a multifunctional formulation that treats several facets of a problem when paired with target-specific synthetic medications. For example,

• • combining aloe vera (which moisturizes and heals wounds) with clotrimazole (an antifungal) to treat fungal skin infections and skin irritation.
  • Ibuprofen has been formulated with Boswellia serrata extract, where the boswellic acids help inhibit leukotriene pathways, augmenting the analgesic effect.
  • Piroxicam paired with ginger extract, as gingerols help in reducing inflammation through cyclooxygenase inhibition, complementing the synthetic action.
  • In the treatment of superficial fungal infections, clotrimazole is often combined with aloe vera gel. Aloe vera not only provides soothing and moisturizing effects but also exhibits mild antifungal activity, enhancing skin recovery.
  • Ketoconazole with neem extract (Azadirachta indica), where neem adds natural antifungal, antibacterial, and anti-inflammatory properties.

These combinations in emulgel formulations aim to create more balanced, effective, and patient-friendly topical therapies, merging modern pharmacology with traditional herbal wisdom.

Formulation Aspects:

Several formulation characteristics must be carefully considered to successfully design an emulgel formulation that incorporates both synthetic and natural medications. Emulgel's dual nature, which consists of both an emulsion and a gel, offers the possibility of combining hydrophilic and lipophilic components, but it also makes obtaining chemical and physical stability more difficult.

1. Selection of Active Ingredients –

The choice of synthetic and herbal drugs must be based on their:

Solubility (lipophilic drugs go into the oil phase, hydrophilic into the aqueous phase)

Stability (sensitivity to heat, light, pH)

Skin irritation must be avoided.

It should be in proper viscosity.

Compatibility with other formulation excipients

For example, lipophilic synthetic drugs like diclofenac may be incorporated into the oil phase, while water-soluble herbal extracts like aloe vera or turmeric hydrosol can be incorporated into the aqueous phase.(23)

2. Emulsion Base Preparation –

Creating an effective emulsion base involves several important formulation aspects to ensure product stability, consistency, and performance across applications like pharmaceuticals, cosmetics, and foods. These considerations include:

• Emulsion Type: Emulsions may be structured as emulsion-filled gels, where oil droplets are dispersed within a gel matrix, or as emulsion particulate gels, which are formed through droplet aggregation. The selection depends on the intended application and desired mechanical and release properties.
• Preparation Technique: Emulsion bases can be prepared by mixing emulsions into a gel or pre-gel solution, followed by inducing gelation, or by designing the formulation to gel under specific stimuli (in situ gelation), such as changes in pH or temperature. Each approach influences the structure and behavior of the final product.
• Emulsifier Choice: The emulsifier type and concentration play a crucial role in stabilizing droplets and determining their interaction with the gel matrix. Proteins and surfactants may either complement or interfere with each other. For instance, excess surfactant may displace proteins from the droplet surface, weakening the overall gel.
• Gelling Agent and Matrix Properties: The type and concentration of the polymer used (e.g., alginate, gelatin, gellan gum) significantly affect gel firmness and water retention. Higher concentrations usually result in a denser, stronger gel network that better retains water and active ingredients.
• Droplet Features: The size and volume of dispersed oil droplets influence the texture and strength of the gel. Smaller droplets increase surface area and improve structural integrity when they bond with the gel matrix. Replacing liquid oils with solid fats can further enhance the gel’s stiffness.
• Responsiveness to Stimuli: Using polymers that react to environmental triggers like temperature or acidity allows for controlled gelation. This is especially useful in oral drug delivery, where gels can form in the stomach and provide sustained release.
• Interface Aging: The time between making the emulsion and forming the gel affects how well droplets bond with the matrix. Longer waiting periods can lead to reduced interaction and weaker gels due to changes in protein structure at the droplet surface.
• Functional Design Goals: The final formulation should meet specific needs, such as drug release behavior, physical stability, or water retention. Tuning the matrix structure and using functional additives enables the development of products with customized performance characteristics.(24)

3. Gelling agent incorporation –

• Choice of Gelling Agent:

In this investigation, hydroxyethyl cellulose (HEC) and natural polymer (Aegle marmelos) were utilized. Natural polymers can improve prolonged release, medication retention, and bioadhesion.

• Evaluation Parameters:

To ensure the gelling agent works effectively, the following are evaluated: Drug content, spreadability, extrudability, swelling index, in vitro drug diffusion, Release kinetics (zero-order, first-order, Higuchi), and ex vivo bioadhesion.

• Final Consideration

Gel texture, application behavior, and treatment efficacy are all greatly impacted by the kind and quantity of gelling agent used. Comparing natural polymers like Aegle marmelos to synthetic ones (like HEC), the former demonstrated superior bioadhesion and sustained release.(25)

4. Drug-Excipient Compatibility –

To determine the compatibility of a drug with excipients for the development of emulgels following methods are used :

• • Visual Observation — Checking for color changes, gas formation, or physical changes.
  • Differential Scanning Calorimetry (DSC) – Detects interactions based on thermal behavior changes.
  • Fourier Transform Infrared Spectroscopy (FTIR) – Identifies chemical structure changes or interactions.
  • High-Performance Thin-Layer Chromatography (HPTLC) – Detects degradation or formation of new compounds.(26)

Compatibility studies (e.g., FTIR, DSC) must be conducted to ensure that the synthetic and herbal actives do not interact negatively with each other or with excipients. Herbal components, being complex mixtures, may interact with emulsifiers or preservatives and affect stability or efficacy.

5. pH and Preservation –

• It is crucial to preserve and protect the normal, physiological pH of the skin. Extrinsic factors are known to influence skin pH, and products administered topically must be understood as task administrators. In light of this, it is important to carefully assess the pH and buffering capability of any product that is applied topically.(27)
• To prevent irritation, the emulgel's pH should be between 5.5 and 6.5, which is the physiological pH of the skin. Natural herbal substances may need to be adjusted because they may affect the final pH.
• Particularly in aqueous systems, preservatives such as methylparaben, propylparaben, or benzyl alcohol are employed to stop microbiological infection. To guarantee compatibility with herbal extracts, caution must be exercised.

6. Use of Permeation Enhancers -

• To boost medication flow through a variety of membranes, such as nasal or stomach epithelia, penetration enhancers can be added to formulations. They ought to be non-irritating, non-toxic, and non-allergic. Ideally, they would operate quickly, and the effect's duration and activity should be predictable and repeatable.(28)
• Permeation enhancers like ethanol, menthol, isopropyl myristate, or essential oils can be added to herbal and synthetic medications to promote skin penetration. Certain botanical ingredients, including clove and eucalyptus oils, naturally improve permeability.
• Particularly helpful in herbal-synthetic emulgel combinations are certain herbal oils, such as neem, clove, and turmeric, which function as natural penetration enhancers. To optimize efficacy while preventing discomfort or instability, careful selection and focus are essential. The bioavailability, effectiveness, and patient acceptance of topical emulgel formulations are all greatly influenced by these enhancers.

7. Stability Considerations –

• To guarantee safety and effectiveness, topical medication compositions need to preserve their physical, chemical, and microbiological stability. Microbial resistance, medication content, viscosity, pH, and appearance are important variables. The stability of topicals based on nanomedicine (such as liposomes and nanoparticles) is also influenced by the drug release profile, surface charge, and particle size. Under different conditions (25°C/60% RH for long-term, 40°C/75% RH for accelerated), stability testing should adhere to ICH norms.⁽²⁷⁾
• To make sure that the formulation does not separate or deteriorate and that the herbal and synthetic medications maintain their effectiveness, stability testing in a variety of conditions (temperature, humidity, and light exposure) is crucial.
• In summary, formulating a stable and effective herbal-synthetic emulgel requires a delicate balance of emulsifying, gelling, and stabilizing components. Each ingredient must be chosen to support the physical integrity, therapeutic efficacy, and patient acceptability of the final product.

Evaluation Parameters:

1. Physical Appearance

Color, homogeneity, consistency, and pH of the produced Emulsion compositions were visually evaluated.

2. Spreadability

For the spreadability test, the spreadability was assessed using both the skin and the glass slide. A second glass slide of the same size was placed over the emulgel and moved toward the end of the first one after two drops of emulgel had been applied to it. Spreading that emulgel evenly was simple. The prepared emulgel was applied to the skin's surface uniformly and without any roughness.(29)

3. Extrudability study

To find out how much force is needed to extrude material from a tube, this empirical test is frequently used. The process for figuring out how much applied shear in the rheogram zone causes plug flow when the shear rate is higher than the yield value. The percentage of emulgel and emulgel extruded from a lacquered aluminum collapsible utilizing the gramme weight needed to extrude at least a 0.5 cm emulgel ribbon in 10 seconds is the basis for the extrudability evaluation of emulgel formulations in this study. As the amount extruded rises, extrudability gets better. The extrudability of each formulation is measured three times, and the average results are shown. The extrudability is then calculated using the following formula:

Extrudability = Weight used to extrude emulgel from tube (in gm) / Area (in cm2).(30)

4. Determination of viscosity

The Brookfield digital viscometer (DV-II +Pro) with spindle number 96 was used to measure the viscosity of the prepared formulations at room temperature at 0.1, 0.5, 1, and 1.5 rpm.(31)

5. Swelling index

Separately, 1 mg of gel is put on porous aluminum foil in a 50 ml beaker with 10 ml of 0.1 N NaOH. After being reweighed, the sample is taken out of the beaker at different times and stored in a dry location for a while.

Swelling index (SW) = [(Wt.-Wo)/Wo] x a hundred.

Where (SW) %= Equilibrium percentage swelling.

Wo= Original weight of emulgel at zero time where time t,

Wt= Weight of swollen emulgel(32)

6. Skin irritation test:

Each site (two sites per rabbit) received a 0.5 g sample of the test material by applying it to a skin region that was roughly 1" x 1" (2.54 x 2.54 cm2) under a double layer of gauze. The rabbit's skin received an application of the Gellified Emulsion. The animals went back to their cages. A 24-hour exposure is followed by the removal of the Gellified Emulsion. Tap water was used to wipe the test sites to get rid of any last bits of test item residue.(33)

7. Stability study:

The emulgels are tested for three months at 50°C, 250°C/60 percent relative humidity, 300°C/65 percent relative humidity, and 400°C/75 percent relative humidity. They are packaged in aluminum collapsible tubes weighing 15 grams. Samples are collected and assessed monthly by ICH standards for a variety of factors, including physical appearance, pH, rheological characteristics, drug content, and drug release profile.(30)

8. Determination of pH:

The formulation's pH was measured with a digital pH meter. To test pH, the pH meter electrode was cleaned with distilled water before being dipped into the mixture three times.(34)

9. Drug Content Determination:

Take 1 gram of the emulgel and dissolve it in an appropriate solvent. Filter the solution to obtain a clear filtrate. Measure the absorbance of this solution using a UV spectrophotometer. A standard calibration curve of the drug should be prepared using the same solvent. The concentration and drug content can then be calculated by substituting the absorbance value into the equation derived from the standard plot:

Drug Content = (Concentration × Dilution Factor× Volume taken) × Conversion Factor. (35)

10.  In Vitro release study:

The modified Franz diffusion (FD) cell was used for the in vitro drug release experiments. The dialysis membrane, which was positioned between the FD cell's donor and receptor compartments, was coated with the formulation. A pH 7.4 phosphate buffer was employed as the dissolving medium. The water jacket circulated to keep the cell's temperature at 37 °C. A magnetic bead was used to constantly agitate the fluid while the entire assembly was held on a magnetic stirrer. As a control, a comparable blank set was run concurrently. At appropriate intervals, the sample (5 ml) was removed and swapped out for equal parts of brand-new dissolving media. Spectrophotometric analysis of the samples was performed at 285 nm, and the cumulative percentage of drug release was computed. The distinction between the readings of drug release and control was used as the actual reading in each case.(17)

Marketed Formulations:

The global market has seen a growing interest in herbal-synthetic emulgel formulations, particularly in dermatology and pain management. While the number of pure emulgel combinations is still limited, several topical products incorporate herbal and synthetic components together in gel or cream-like bases, and newer emulgels are emerging due to their enhanced efficacy and patient compliance. Several commercially available products utilize a combination of synthetic drugs (like diclofenac or ketoprofen) with herbal ingredients (such as menthol, eucalyptus oil, or linseed oil). Popular examples include:

• Diclogel Plus (diclofenac + menthol + linseed oil)
• Fastum Gel (ketoprofen + herbal oils)
• Moov and Himalaya Pain Relief Gel (herbal blends in gel bases)

Although not always labeled as “emulgels,” many of these products utilize emulsion-in-gel systems for enhanced delivery. Examples include formulations of diclofenac with clove oil, curcumin with NSAIDs, and benzoyl peroxide with herbal extracts. These patented innovations often aim to reduce side effects and increase therapeutic efficacy. The need for multifunctional topical medicines that are both skin-friendly and efficacious is driving a rapid expansion of the herbal-synthetic emulgel formulations' commercial and intellectual property landscape. The patent field shows considerable progress in real emulgel systems, particularly for pain, inflammation, and dermatological problems, even if marketed goods still primarily use straightforward herbal-synthetic gel combinations.

Challenges and Limitations:

• Incompatibility Between Herbal and Synthetic Components: Physicochemical incompatibility between synthetic drugs and herbal extracts can affect formulation stability. Herbal extracts often contain multiple bioactives, making it hard to predict interactions with synthetic APIs or excipients. Risk of precipitation, phase separation, or degradation during storage.
• Standardization and Quality Control of Herbal Ingredients: Variability in plant source, harvesting time, and extraction methods leads to inconsistent active compound content. Lack of standardization affects reproducibility, dose accuracy, and therapeutic efficacy. Herbal ingredients may also carry contaminants (e.g., heavy metals, microbes, pesticides).
• Stability Issues: Emulgel systems are sensitive to changes in pH, temperature, and light. Herbal compounds (like curcumin or essential oils) are often unstable or prone to oxidation. Ensuring the long-term stability of a dual-acting system is complex and requires antioxidants, preservatives, and proper packaging.
• Skin Irritation and Allergic Reactions: Herbal components, though natural, can still cause irritation, hypersensitivity, or photosensitization. Combining synthetic drugs (especially NSAIDs or steroids) with certain essential oils may increase the risk of skin reactions. Safety testing becomes more complicated due to the multi-component nature of the formulation.
• Regulatory Hurdles: Lack of harmonized guidelines for herbal-synthetic combinations makes regulatory approval difficult. Products may fall under multiple regulatory categories (herbal, pharmaceutical, cosmeceutical), complicating classification. Limited clinical data are available on combined efficacy and safety, increasing the burden for new product approval.
• Limited Clinical Evidence: While traditional use supports the efficacy of many herbs, scientific validation in combination with synthetic drugs is often lacking. Few clinical trials specifically study herbal-synthetic emulgels, which limits physician confidence and product acceptance.
• Manufacturing and Scalability: Combining oil-in-water emulsions with gel bases requires careful control of process parameters. Incorporating multiple actives without affecting viscosity, spreadability, or penetration is technically demanding. Ensuring homogeneity at scale can be a major limitation.

The formulation of herbal-synthetic emulgels presents exciting opportunities, but is challenged by issues related to compatibility, standardization, safety, stability, and regulation. Overcoming these barriers will require interdisciplinary approaches, involving phytochemistry, formulation science, regulatory affairs, and clinical validation.

CONCLUSION:

The integration of herbal and synthetic drugs into emulgel formulations represents a promising advancement in topical and transdermal drug delivery. Emulgels combine the benefits of both emulsions and gels, offering improved drug penetration, controlled release, patient compliance, and ease of application. By harnessing the synergistic effects of herbal bioactives and synthetic compounds, such formulations can enhance therapeutic efficacy while potentially reducing side effects. However, the development of such systems is not without challenges. Issues such as incompatibility, stability concerns, standardization of herbal ingredients, and regulatory complexities continue to limit their broader clinical adoption. Despite these limitations, growing scientific interest, consumer preference for natural therapies, and advances in formulation technology—including nanotechnology, quality control, and personalized medicine—are driving the field forward. The future holds strong potential for herbal-synthetic emulgels in diverse therapeutic areas such as pain relief, dermatology, wound healing, and cosmeceuticals. Continued interdisciplinary research, supported by robust clinical validation and regulatory evolution, is essential to fully realize the potential of these hybrid systems. As science and tradition converge, herbal-synthetic emulgels may become a key innovation in modern pharmaceutics.

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