Anti-Inflammatory Emulgels: Emerging Trends and Future Perspectives in Topical Drug Delivery System

Abstract

Topical drug delivery for inflammatory conditions has advanced considerably with the introduction of emulgel formulations. Emulgels, which combine the beneficial properties of emulsions and gels, provide improved drug stability, enhanced skin penetration, and user-friendly application. This review presents a detailed overview of current developments in anti-inflammatory emulgels, covering formulation techniques, underlying mechanisms, and evaluation methods. It emphasizes the benefits of emulgels compared to traditional topical dosage forms, particularly their capacity to efficiently deliver both water- and oil-soluble drugs. However, challenges such as maintaining formulation stability, controlling drug release, and ensuring skin compatibility persist. The review also discusses future directions, including the use of novel excipients, incorporation of nanotechnology, and personalized treatment strategies to enhance therapeutic efficacy. By summarizing existing research and highlighting areas needing further study, this article serves as a comprehensive guide for researchers developing advanced topical anti-inflammatory treatments.

Keywords

Introduction

Fig 1. Structure of skin

OVERVIEW ON EMULGEL

A specific topical formulation known as an emulgel is made by mixing an emulsion with a gel base. It is crucial for topical medication administration because of its dual release mechanism, which combines gel and emulsion systems [22]. These emulgels have several desirable qualities for dermatological applications, such as a non-greasy texture, ease of spreadability and removal, emollient properties, non-staining qualities, longer shelf life, transparency, attractive appearance, and a lower chance of serious side effects [23]. A gelling agent can stabilize an emulgel made as either water dispersed in oil (w/o) or oil dispersed in water (o/w). It provides a reliable and efficient platform for incorporating drugs that are poorly soluble in water [24]. Emulgel can handle both lipophilic and hydrophilic drugs because of its dual aqueous and non-aqueous phases. By using a biphasic approach to increase drug loading capacity and stability, it also serves as a controlled-release formulation [25]. It functions as a dual-controlled release mechanism, combining the advantageous qualities of emulsions and gels for improved efficacy and delivery [26]. Emulgels are emulsions—either water-in-oil or oil-in-water—that gel upon contact with a gelling agent [27]. Emulsified gels are superior and stable carriers for hydrophobic or poorly water-soluble drugs. Emulsion and gel are combined to create short emulgels [28]. One of the key limitations of gels’ many benefits is their reduced capacity for administering hydrophobic drugs [29].

Delivery of Drug Through Emulgel

By encapsulating drug particles in their internal phase, emulsions serve as controlled-release drug delivery systems that ensure a steady and gradual release of the medication. This configuration allows the drug to slowly permeate the skin and diffuse through the emulsion’s outer layer, resulting in prolonged release that enhances the drug’s efficacy by promoting gradual and sustained absorption. A cross-linked gel network effectively traps small particles and supports regulated drug release, ensuring a consistent supply of the active ingredient over time. Furthermore, the mucoadhesive properties of these formulations extend the duration the drug remains in contact with the skin, further improving therapeutic outcomes. The emollient properties of water-in-oil emulsions make them particularly suitable for treating dry skin disorders [30].

Bottom of Form

Types of Emulgel

Microemulsion Gel [31]

A microemulsion gel is a biphasic oil-in-water formulation stabilized by surfactants, offering optical clarity and thermodynamic stability. The droplets, ranging in size from 10 to 100 μm, are composed of precise proportions of water, surfactant, co-surfactant, and oil. Microemulsions are characterized by high surface area, low interfacial tension, and the ability to dissolve both water- and oil-soluble substances. These properties enhance drug penetration by reducing the stratum corneum's barrier, making them beneficial for transdermal drug delivery. To address the challenge of viscosity and stability, gelling agents such as Guar gum, HPMC K100M, and Carbopol 940 are incorporated into microemulsions to form microemulsion-based gels.

Nanoemulsion Gels [32]

Nanoemulsion gels are clear oil-in-water dispersions stabilized by surfactants and co-surfactants, with globule sizes ranging from 1 to 100 nm. When combined with a gel base, they form nanoemulgels. Nanoemulsions significantly enhance transdermal and dermal drug delivery—both in vitro and in vivo—compared to traditional emulsions and gels. Their high drug-loading capacity and small droplet size improve drug absorption through the skin, leading to a faster onset of therapeutic action.

Macroemulsion Gel [33–35]

Macroemulsion gels are emulgels containing emulsion droplet particles larger than 400 nm. While the droplets are not visible to the naked eye, they can be observed under a microscope. Despite being thermodynamically unstable, macroemulsions can be stabilized using surface-active agents. These gels serve as carriers for drugs in topical formulations where larger droplet sizes are acceptable or required.

Advantages of Emulgel [36]

1. Incorporation of hydrophobic drugs
2. Enhanced drug loading capacity
3. Improved stability
4. Controlled and sustained drug release
5. No need for intense sonication during preparation
6. Bypasses first-pass metabolism
7. Avoids gastrointestinal incompatibility
8. Increased site-specific delivery
9. Better patient compliance
10. Easy to apply and user-friendly

Disadvantages of Emulgel [37]

1. Potential for contact dermatitis or skin irritation
2. Risk of allergic reactions
3. Limited skin permeability for certain drugs
4. Difficulty absorbing drugs with large particle sizes
5. Formation of bubbles during preparation

Composition of Emulgel

Drug – The way a medication penetrates through the skin is mostly determined by its inherent properties. When creating an emulgel for topical or transdermal application, a number of the drug's physicochemical and biological characteristics are essential. When a medication has an appropriate partition coefficient (log) between 0.8 and 5, its ability to cross epidermal barriers is improved. This suggests that the medication is well distributed in lipids and water. In addition to being non-irritating and having a skin permeability coefficient of 0.5×10?³ cm/h, the drug's low polarity makes absorption easier.[38]

Vehicle – Both aqueous and oily carriers are utilized to handle hydrophilic and hydrophobic medicines in the preparation of an emulgel. In order to provide a well-balanced formulation, aqueous phase vehicles—such as alcohol, water, and other water-based substances—help dissolve and assimilate hydrophilic medications, while oily vehicles aid with hydrophobic drugs.[39]

Oils – The formulation is created by combining a number of ingredients during the oily phase of emulsion manufacturing. For external uses, mineral oils can be used alone or in combination with hard or soft paraffin to deliver medications. These oils have occlusive properties that help retain moisture and give the emulsions sensory features. On the other hand, oils used in oral preparations, such as castor and mineral oils, are not recyclable and often have a localized laxative effect. Fish liver oils and a range of vegetable oils, such as those from corn, cotton seed, and archies, are commonly used in dietary supplements due to their nutritional benefits and distinct health properties.[40]

Emulsifiers – For emulsification to proceed smoothly during the manufacturing process, emulsifying agents are necessary. Additionally, they support emulsion stability throughout time. Commercial formulations can stay stable for months or even years, whereas formulated emulsions can endure for days. Stearic acid, sodium stearate, polyethylene glycol (PEG), 4031 stearate, sorbitan monooleate (Span 80), and polyoxyethylene sorbitan monooleate (Tween 80) are a few examples.[41]

Gelling Agent – These compounds serve as thickening agents and increase the viscosity of different dosage forms, improving the formulations' stability and uniformity. They contribute significantly to the preparation of emulgels by giving the formulation its viscosity, stability, and rheological characteristics. They serve to turn the emulsion into a semi-solid gel matrix, boosting its spreadability, adherence and retention on the skin, thereby optimizing drug administration and therapeutic efficacy.[42]

Types of Gelling Agent

Natural polymer – Proteins (gelatin, collagen, egg whites, and casein) and polysaccharides (guargum, acacia gum, tragacanth gum, pectin, starch, xanthan gum, dextran, succinogluconate, etc.) are examples of natural polymers.

Semi Synthetic Polymers – These polymers, which include carboxymethylcellulose, hydroxylpropylcellulose, ethylcellulose, hydroxyethylcellulose, silicate (Veegum®), methylcellulose, sodium alginate, and carbopol-940, contain both natural and manufactured polymers.

Synthetic Polymers – These are entirely synthetic and produced on a bigger scale in a lab, such as polyvinyl alcohol, poloxamers (Pluronics®), and carbopols® (now known as carbomers).[43]

Permeation enhancer

By allowing medications to pass through biological barriers like the skin or mucous membranes, penetration enhancers increase drug delivery systems. These enhancers improve the therapeutic results of topical and transdermal medications by increasing drug bioavailability and efficacy.

Features of Permeation enhancer:

• They must be non-allergic, safe, and kind to the skin.
• They shouldn't have any therapeutic effects on the body or stick to receptor locations.
• Penetration enhancers are supposed to make it easier for pharmaceuticals to enter the body and prevent endogenous materials from being lost.[43]

Co-surfactants: Surfactants with single chains alone cannot sufficiently reduce the oil-to-water interfacial tension. Therefore, to enable emulsification, various co-surfactants are used such as propylene glycol (PG) and cetostearyl alcohol.[43]

Preservatives – Preservatives are necessary to stop microorganisms from growing. Parabens such as methyl, propyl, benzyl, butyl, and p-hydroxy benzoate are commonly used for this.[43]

Methods for preparation of Emulgel

Fig 2. Methods for preparation of emulgel

Methods for preparing emulgel involve three main steps:

• Step 1: Preparation of the emulsion, which can be either oil-in-water (O/W) or water-in-oil (W/O).
• Step 2: Preparation of the gel base separately.
• Step 3: Gradual mixing of the emulsion into the gel base with constant stirring to achieve a uniform emulgel formulation.

There are three primary steps in the straightforward process used to prepare emulgel. To create emulgel, the first two processes are to formulate the emulsion and gel base independently, then incorporate the emulsion into the gel base. The aqueous phase of the emulsion formulation is first made by dissolving emulsifying agents such as Tween 20 or hydrophilic surfactants in distilled water. Likewise, emulsifying agents such as Span 20 or lipophilic surfactants are dissolved in oil (liquid paraffin) to create the oil phase. After being heated independently to a temperature between 70° and 80°, the oil and aqueous phases are combined while being constantly stirred to create an emulsion. Dispersing gelling chemicals, such as Carbopol or HPMC, into distilled water creates the gel phase. In order to create emulgel, the emulsion and gel phase are finally combined in a 1:1 ratio while being gently stirred.[44]

EVALUATION OF EMULGEL[43]

Visual examination

The prepared formulation is visually examined to assess its color, texture, and uniformity in order to evaluate its physical characteristics.

Homogeneity

Assessing homogeneity involves looking at the gel's appearance and looking for any aggregates in formulation.

pH

To ascertain the emulgel's pH, dissolve it in water to create a 1% solution first. Next, use a digital pH meter to measure this solution's pH in order to get an accurate reading.

Spreadability

Spreadability was assessed by applying an excess of sample on each of the two glass slides, which was then compacted to a consistent thickness using a 1 kg weight for five minutes.

A precise 50 g weight was added to the lower plate. The measure of spreadability was the amount of time needed to spread the two slides, or the amount of time it took for the upper glass slide to pass over the lower plate.

Spreadability (S) = M × L / T

where L is the length traveled on the glass slide, T is the time required, and M is the weight tide to the top slide.

Drug content determination

Dissolve 1 gram in 100 milliliters of solvent to find the amount of drug present in the emulgel. Filtering the solution and then appropriately diluting it for spectrophotometric measurement will produce clarity.

Centrifugation Analysis

By mimicking high-speed circumstances, the centrifugation technique is used to evaluate the stability of emulgel formulations. This method, which is usually carried out a week following the emulgel's creation, aids in determining whether the formulation stays stable or if any phase separation or changes take place over time. Centrifuging the emulgel for 30 minutes at 3000 rpm is required for the stability evaluation. Centrifugation 71 can be used to detect any phase separation, sedimentation, or instability inside the emulgel.

Viscosity determination

The digital viscometer (Brookfield), which has a cone and plate arrangement, was used to measure the viscosity of several emulgel formulations at room temperature. This tool provides crucial information on the consistency of the emulsion by precisely measuring how thick and flow-resistant it is. The spindle was allowed to rotate freely in the emulgel when the viscosity reading was taken. Spindle 6 is used to measure the viscosity of emulgel at 100 rpm.

Skin irritation test: For topical dose forms, a skin irritation test is required. to assess irritability following a single topical emulgel treatment. After applying the optimal formulation to the skin (3 cm2), reactions like erythema and edema are measured and graded 24 hours later. After a day, the emulgel is taken off, and the treatment areas are cleaned.

Extrudability study

Extrudability is measured by the force needed to push emulgel out of a tube. The method determines the applied shear in that region and states that plug flow happens when the shear rate exceeds the yield value. In this experiment, the emulgel is extruded using a collapsible metal tube. The weight in grams needed to extrude an emulgel ribbon in ten seconds is measured in order to determine extrudability. Better extrudability is indicated by a higher weight. To guarantee measurement accuracy, this procedure is carried out three times, and the average value is computed. The following formula is used to determine extrudability. The formula for calculating extrudability is area (cm2) divided by weight (g) used to extrude emulgel from the tube.

Globule Size and Distribution in Emulgel

The globule size and distribution within the sample are ascertained using the Zetasizer instrument. A one-gram sample is dissolved in filtered water and then thoroughly mixed by spinning to produce a uniform dispersion. Using the zetasizer, this procedure guarantees precise assessment of the globule properties. This sample is then put into the zetasizer's photocell, and the distribution and mean globule diameter are determined.

In vitro cumulative drug release studies by percentage

 To prepare the egg's outer shell membrane, the calcified layer is dissolved by submerging the egg in a 50% aqueous solution of HCl. To remove the contents of the egg, the membrane is carefully cut, and the contents are then washed with regular saline solution. The inner membrane is kept in distilled water after being frequently cleaned with water. After cutting the necessary length of egg membrane and tying it with thread to the diffusion cell's bottom (grounded) layer, it is put in a beaker with 100 milliliters of 5.5 pH phosphate buffer. To stir the contents during the studies, a magnetic bead is added to the outer compartment. The complete system is placed in a magnetic stirrer and temperature

Swelling index

The formulation with the highest swelling index is capable of absorbing exudates from wounds. To determine the swelling index, 1g of emulgel is placed in a petridish with 10 ml of 0.1 N NaOH and covered with permeable aluminum foil. The samples are taken at different times, given a little time to dry, and then weighed. Next, the swelling index is computed using a formula. The index (????????) % is equal to [(????????−????????)/????????] ×100. where Wo is the initial weight of the emulgel at zero time, (SW) % is the equilibrium swelling percentage, and Wt is the weight of the swollen emulgel after a predetermined amount of time.

Analysis of stability

Stability is the capacity of a drug formulation to maintain its unique chemical, physical, toxicological, and therapeutic characteristics inside a certain container. All stability investigations are conducted in accordance with ICH guidelines.

INFLAMMATION[45,46]

Inflammation is a protective reaction involving immune cells, blood vessels, and chemical mediators that occurs when bodily tissues react to hazardous stimuli like pathogens, damaged cells, or irritants. Inflammation serves to remove the initial source of cell damage, remove necrotic cells and tissue that has been harmed by the first insult and the inflammatory process, and promote initial tissue restoration.Inducers, mediators, effectors, and sensors make up the inflammatory pathway. Both infectious and non-infectious stimuli, including poisons, foreign objects, necrotic cell signals, and damaged tissue, can act as inducers. The inducer activates sensors, which are specialized molecules that cause mediators to be produced. Endogenous substances known as mediators have the ability to activate effector tissue and cells, cause pain, and either stimulate or inhibit inflammation and tissue repair. Numerous other pathways in the inflammatory pathway are created by the conjugation of these multiple participants, and the stimuli that are included determine which path is chosen. One of the objectives of a sterile stimulation is to keep the wounded tissue from becoming infected. Pathogen associated molecular patterns (PAMPs), which are molecules from pathogenic organisms, and damaged associated molecular patterns (DAMPs), which are molecules generated from host cells that have been damaged, are two categories of inducers. Different receptors in dendritic and macrophage cells recognize these patterns, and pain receptors also detect injured tissue. When such receptors are stimulated, inflammatory cytokines are produced. These include, among others, TNF-alpha, IL-10, and IL-6, which alter the endothelium and let immune cells to pass through the junction between the junctions.The immune cells that rely on the tissue's level of inflammation While full-blown inflammation also causes neutrophils to migrate to the tissue, para-inflammation results in the recruitment of monocytes. Enzymes that combat infectious organisms and eliminate dead cells will subsequently be released by these cells. Reactive oxygen species (ROS) will build up in tissue as a result of this enzyme release. They are referred to as "damaged healthy cells." Additionally, pro-inflammatory cytokines released by endothelial cells draw in more inflammatory cells. Additionally, plasma moves to nearby tissues, causing tissue edema. Anticoagulant protein production is decreased, and circulating platelets are also activated and aggregate. This may result in intravascular thrombosis, which may cause organ failure if it occurs in excess.

Causes of inflammation[47]

• • Pathogen like bacteria, viruses, or fungi
  • External injuries like damage through foreign object.
  • Effect of chemicals or radiation.

Signs of inflammation[48]

Acute inflammation might manifest as any one of five symptoms.

1. 1. Redness: This is caused by the area's blood vessels being overflowing with blood.
   2. Heat: As more blood flows to the afflicted area, heat is generated, making the area feel warm to the touch.
   3. Pain: It's likely that the irritated region will hurt, especially when touched. Due to the chemicals released during the inflammatory process, nerves become more sensitive and stimulated.
   4. Loss of function: The impacted area may experience some loss of function. Examples include having trouble breathing if you have a respiratory infection or being unable to move an inflammatory joint.

Types of inflammation[48]

1. Acute inflammation

The healing process begins when the body reacts by releasing cytokines, which are proteins that increase inflammation. Acute inflammation is frequently brought on by trauma, dangerous substances, or microbial invasion (i.e., bacteria and viruses). Acute inflammation happens quickly, can be severe, and lasts for a brief amount of time. While signs and symptoms may last a few days, more serious causes may cause them to last longer.

Five distinct symptoms are often caused by acute inflammation. These consist of:

1. Appearance of red colour
2. Heat;
3. Swelling;
4. Pain

2. Chronic inflammation

Long-term inflammation that lasts for months to years is called chronic inflammation. An autoimmune condition, in which the immune system targets its own healthy tissues because it believes they are ill, is typically the source of chronic inflammation. Additionally, low-level exposure to irritants such industrial chemicals might result in chronic inflammation. whether it resulted in an acute inflammation, as is the case with disease or infection, or over extended periodsof time or failure to cure.

Compared to acute cases, chronic inflammation symptoms typically manifest differently. Acute inflammation may be followed by chronic inflammation, or it may start slowly. It lasts longer and is linked to tissue damage, fibrosis, blood vessel proliferation, and the presence of macrophages and lymphocytes.

Symptoms  are

• Fatigue
• Chest pain
• Fever
• Rash
• Muscle pain
• Joint pain

Treatment of inflammation depend on[49]

1. Types of Inflammation

• Acute – Short-term inflammation often triggered by injury or infection.
• Chronic – Long-lasting inflammation typically associated with conditions like autoimmune or metabolic disorders.

2. Underlying Causes

• Infectious – Caused by bacteria, viruses, or other pathogens.
• Autoimmune – The immune system mistakenly attacks the body’s own tissues.
• Metabolic – Linked to disorders like obesity or diabetes.
• Allergic – Triggered by hypersensitive immune reactions to allergens.

3. Affected Body Systems

• Joints – As seen in arthritis or gout.
• Gastrointestinal Tract – Such as in inflammatory bowel disease (IBD).
• Skin – Conditions like eczema or psoriasis.
• Central Nervous System (CNS) – Seen in diseases like multiple sclerosis.

NSAIDs (Nonsteroidal Anti-inflammatory Drug)[48]

NSAIDs (nonsteroidal anti-inflammatory medications) have antipyretic and analgesic effects. Oral NSAIDs are useful for treating a range of acute and chronic pain conditions, but using them can have major side effects, especially gastrointestinal disorders. For a number of clinical indications, transdermal distribution of NSAIDs has proven to be a practical method of administration. Furthermore,  applying gel as a method of delivery. can give a quicker release of the drug's ingredient and lengthen the time it stays on the skin. In most cases, extensive preformulation experiments are required to maximize both skin penetration and medication release from the topical carrier.

Classification of NSAIDs

Mechanism action of NSAID’S⁴⁸

NSAIDs reversibly block the cyclooxygenase (also known as prostaglandin endoperoxide synthase, or COX) enzyme, which is now known to have two isoforms, COX-1 and COX-2, that mediate prostaglandin synthesis.

Advantages of topical NSAID’S  formulation[48]

• • Topical treatment may improve adherence since it is more palatable to the patient.
  • Permission to administer medication to patients who cannot swallow or tolerate oral formulation.
  • It's easier to administer than other routes, it can be more economical.
  • Preventing interactions between drugs.
  • The removal of dosage titration may result in a shorter time to efficacy.

ANTI-INFLAMMATORY EMULGELS[50]

The characteristics of an emulsion (oil-in-water or water-in-oil) and a gel base are combined in an anti-inflammatory emulgel, a topical medication delivery device. It is intended to alleviate inflammation, discomfort, and swelling locally by delivering anti-inflammatory medications through the skin.

RATIONALE BEHIND USE OF EMULGELS FOR INFLAMMATION

1. Targeted Localized Treatment[50]

Emulgels enable direct delivery of anti-inflammatory drugs to the affected area, such as the skin, muscles, or joints. This localized approach limits systemic drug absorption, thereby reducing the side effects often associated with oral anti-inflammatory medications.

2. Improved Drug Absorption and Effectiveness[51]

The combination of emulsion and gel phases in emulgels allows for the efficient delivery of both water-soluble and fat-soluble drugs. The presence of oils and permeation enhancers further facilitates drug penetration through the skin, boosting therapeutic effectiveness.

3. Enhanced Patient Acceptability[43]

Thanks to their non-greasy, smooth texture, emulgels spread easily and absorb quickly into the skin. This makes them more comfortable and user-friendly compared to greasy ointments or creams, leading to better patient compliance.

4. Less Frequent Application Needed[52]

Emulgels provide controlled and sustained release of drugs, which extends their duration of action and reduces the frequency of application.

5. Broad Range of Drug Compatibility[53]

Emulgels can incorporate various anti-inflammatory agents, ranging from synthetic NSAIDs like diclofenac to natural compounds such as curcumin, allowing for tailored treatment options.

Marketed formulations of emulgel for inflammation[53]

Reported  herbal drug emulgels and their efficacy⁵³

NOVEL FORMULATION OF  ANTI-INFLAMATORY EMULGEL ARE

1. Nanoemulgel-based anti-inflammatory formulation[54]

Concept: Embed nanoemulsion droplets into a gel base to enhance drug delivery by improving penetration, stability, and providing controlled release.

Novelty: The presence of nano-sized oil droplets boosts skin absorption and increases the drug’s bioavailability.

2. Herbal extract-based emulgel with synergistic actives[55]

This formulation integrates multiple plant-derived anti-inflammatory compounds such as:

• • Boswellia serrata extract (rich in boswellic acids)
  • Turmeric/ Curcumin
  • Ginger extract (containing gingerols)
  • Aloe vera

Novelty: Offers a broad-spectrum, natural anti-inflammatory effect through synergistic action of multiple botanicals, resulting in enhanced efficacy with minimal side effects.

3. Stimuli-responsive (thermoresponsive) emulgel[55]

Incorporate thermoresponsive polymers such as Poloxamer 407, which stay in a liquid state at room temperature but transition into a gel when exposed to skin temperature (around 32°C). This improves ease of application and creates a protective gel layer once applied.

4. Liposome or niosome-loaded emulgel

Incorporate the anti-inflammatory drug within liposomes or niosomes to achieve:

• • Improved penetration through the skin
  • Controlled and prolonged drug release
  • Minimized skin irritation

CURRENT THERAPEUTIC APPROACHES FOR INFLAMATION

1. Pharmacological Management of Inflammation

A. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)[56]

• • Examples: Ibuprofen, Naproxen, Diclofenac, Aspirin
  • Pharmacodynamics: Act by inhibiting cyclooxygenase isoenzymes (COX-1 and COX-2), leading to decreased prostaglandin synthesis and attenuation of inflammatory responses.
  • Clinical Use: Management of mild to moderate pain, fever, musculoskeletal inflammation, and inflammatory arthropathies.
  • Adverse Effects: Gastrointestinal mucosal damage, peptic ulceration, nephrotoxicity, and increased cardiovascular risk with prolonged administration.

B. Corticosteroids[57]

• • Examples: Prednisone, Dexamethasone, Hydrocortisone
  • Mechanism of Action: Modulate gene expression by inhibiting nuclear factor-kappa B (NF-κB) and other transcription factors; suppress cytokine release, COX-2 expression, and leukocyte infiltration.
  • Indications: Indicated in severe or systemic inflammatory and autoimmune conditions (e.g., rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel diseases, asthma).
  • Limitations: Risk of immunosuppression, hyperglycemia, osteoporosis, adrenal suppression, and iatrogenic Cushing's syndrome with chronic use.

C. Disease-Modifying Anti-Rheumatic Drugs (DMARDs)[58]

• Categories:

• Conventional synthetic DMARDs: Methotrexate, Sulfasalazine
• Biologic DMARDs: TNF-α inhibitors (e.g., Infliximab), IL-6 receptor blockers (e.g., Tocilizumab)
• Targeted synthetic DMARDs: Janus kinase (JAK) inhibitors (e.g., Tofacitinib)

• Mechanism: Modify underlying disease pathophysiology by targeting immune pathways; reduce joint damage and progression in autoimmune conditions.
• Use: First-line or adjunctive therapy in chronic inflammatory disorders such as rheumatoid arthritis and psoriatic arthritis.
• Risks: Immunosuppressive effects, infection susceptibility, high cost, and long-term safety monitoring requirements.

D. Analgesics with anti-inflammatory adjunct properties[59]

• • Examples: Paracetamol (acetaminophen), opioid analgesics
  • Utility: Employed when NSAIDs are contraindicated; provide analgesia with minimal anti-inflammatory effect (paracetamol).
  • Considerations: Opioids modulate nociceptive signaling but carry high potential for dependency and do not exert true anti-inflammatory action.

2. Topical anti-inflammatory therapeutics[60]

• Application: Effective for localized inflammatory conditions such as osteoarthritis, dermatological inflammation, and musculoskeletal disorders.
• Agents:

• Topical NSAIDs (e.g., Diclofenac sodium gels/emulgels)
• Capsaicin cream (TRPV1 receptor agonist)
• Phytochemical-based formulations (e.g., curcumin, Boswellia serrata)

• Recent Advances: Utilization of advanced drug delivery systems (e.g., liposomes, niosomes, nanoemulgels) to enhance percutaneous absorption, sustain drug release, and minimize systemic exposure.

3. Biologic therapies and immunomodulators[61]

• Mechanism: Recombinant monoclonal antibodies or fusion proteins targeting specific cytokines or immune cells involved in inflammatory signaling.
• Molecular Targets:

• TNF-α (e.g., Adalimumab)
• Interleukins (IL-1, IL-6, IL-17 inhibitors)
• B-cell depletion (e.g., Rituximab)

• Indications: Moderate-to-severe autoimmune conditions including rheumatoid arthritis, Crohn’s disease, and psoriasis.
• Future Perspective: Emergence of precision immunotherapies, including CRISPR-edited immune cells and individualized biologic regimens.

4. Natural and phytopharmaceutical approaches[61]

• Key Phytoconstituents:

• Curcumin (from Curcuma longa)
• Boswellic acids (from Boswellia serrata)
• Gingerols (from Zingiber officinale)
• Aloe vera extracts

• Mechanism: Antioxidant, anti-inflammatory, and NF-κB/COX-2 pathway inhibition.
• Formulations: Orally (capsules, tinctures), topically (creams, gels, nanoemulsions).
• Limitations: Variability in bioavailability, lack of standardization, and regulatory constraints.

5. Lifestyle & non-pharmacological interventions

A. Dietary interventions[62]

• • Anti-inflammatory dietary regimens: Mediterranean, DASH, and plant-based diets
  • Focus: Enhanced intake of omega-3 fatty acids, polyphenols, and antioxidants; reduction in pro-inflammatory foods (refined sugars, processed fats).

B. Physical activity[63]

• • Effect: Lowers systemic inflammatory biomarkers (e.g., CRP, IL-6); supports joint mobility and reduces stiffness in chronic inflammatory disorders.

C. Stress management[64]

• • Methods: Yoga, mindfulness, CBT
  • Rationale: Chronic psychological stress contributes to elevated pro-inflammatory cytokines via HPA axis dysregulation.

6. Emerging & targeted therapies

A. Nanomedicine & Advanced Drug Delivery Systems[65]

• • Systems: Liposomes, niosomes, nanoemulsions, dendrimers
  • Advantages: Targeted site-specific delivery, improved bioavailability, prolonged release, and reduced systemic toxicity.

B. Gene-based therapies[66]

• • Mechanism: Use of siRNA, miRNA, or gene editing tools to downregulate pro-inflammatory gene expression.
  • Status: Primarily investigational; ongoing clinical trials.

C. Microbiome modulation[67]

• • Approaches: Probiotics, prebiotics, fecal microbiota transplantation (FMT)
  • Objective: Restoration of gut-immune homeostasis, particularly relevant in inflammatory bowel disease (IBD) and rheumatoid arthritis.

RECENT ADVANCES IN EMULGEL FORMULATIONS FOR ANTI-INFLAMMATORY APPLICATIONS

1. Improved drug penetration AND controlled release[68]

Recent investigations have shown that emulgel systems significantly enhance the percutaneous absorption and provide sustained release of active pharmaceutical ingredients (APIs). For example, research on posaconazole-loaded emulgels demonstrated superior dermal delivery compared to traditional topical formulations, addressing common limitations in skin penetration.

2. Integration of nanotechnology[69]

The incorporation of nanocarriers, such as nanoemulsions, into emulgel formulations has been extensively studied to improve the solubility, stability, and bioavailability of lipophilic drugs. These nanoemulsion-based gels enable dual release mechanisms—combining both emulsion and gel phases—offering an advanced platform for efficient topical drug delivery.

3. Critical formulation parameters[69]

The therapeutic efficacy of emulgels is highly dependent on the careful selection of formulation components, including gelling agents, surfactants, and permeation enhancers. Optimizing these excipients is essential to achieve desirable rheological characteristics, formulation stability, and enhanced skin permeation.

4. Enhanced patient compliance and clinical utility[70]

Emulgels are increasingly favored in dermatological therapy due to their favorable physicochemical properties, such as non-greasiness, transparency, and ease of application, which collectively improve patient adherence. Their efficacy in managing inflammatory dermatoses further emphasizes their growing clinical relevance.

PHARMACEUTICAL CHALLENGES IN FORMULATING AND COMMERCIALIZING EMULGELS FOR MANAGEMENT OF INFLAMMATION[72]

Physical and chemical stability

Emulgel formulations frequently encounter stability problems such as phase separation, creaming, and sedimentation during storage, which can compromise their uniformity. Additionally, degradation processes like oxidation and hydrolysis of both active ingredients and excipients may diminish the product’s efficacy and shelf life. Maintaining stable viscosity and rheological properties over extended periods is also challenging, especially when exposed to fluctuations in temperature and humidity.

Drug loading and controlled release

Formulating emulgels with sufficient drug loading, particularly for poorly water-soluble or hydrophobic anti-inflammatory compounds, remains difficult due to solubility limitations. Achieving controlled and sustained drug release without an initial burst effect requires careful optimization of the formulation components. Furthermore, the use of permeation enhancers must be balanced to improve skin absorption without inducing irritation or toxicity.

Manufacturing and scale-up

Translating lab-scale emulgel production techniques, such as homogenization and sonication, to industrial manufacturing poses reproducibility and scalability challenges. Ensuring consistent batch-to-batch quality, including parameters like particle size distribution and viscosity, during large-scale production is a critical hurdle.

Regulatory and quality control issues

The absence of well-defined regulatory guidelines tailored specifically for emulgels complicates the approval process. Characterization protocols for formulations containing nanocarriers or novel excipients are still under development. Additionally, the safety and efficacy evaluation of emerging bioactive phytoconstituents necessitates thorough toxicological and clinical studies.

Patient-centred challenges

There is a risk of skin irritation or allergic reactions stemming from excipients or penetration enhancers used in emulgels. Unfavorable sensory properties such as greasiness, odor, and poor spreadability can negatively impact patient compliance. Moreover, there is limited long-term safety data available for chronic use of emulgel formulations in inflammatory conditions.

FUTURE PROSPECTS OF ANTI-INFLAMMATORY EMULGELS

The future of anti-inflammatory emulgel development is expected to be shaped by technological innovations and the evolving needs of patient-centric therapeutics. As pharmaceutical sciences advance, emulgels are poised to offer more efficient, targeted, and user-friendly treatment modalities for a wide spectrum of inflammatory disorders. The following key areas highlight potential directions for future research and development:

1. Integration of nanotechnology-based delivery systems[73]

Emulgel formulations incorporating nanocarriers—such as nanoemulsions, liposomes, niosomes, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs)—are likely to gain further traction. These systems enhance the solubility of lipophilic anti-inflammatory drugs, improve dermal penetration, and allow for sustained and site-specific drug release. Future studies may focus on optimizing formulation parameters to improve drug entrapment, minimize systemic absorption, and ensure precise delivery at the site of inflammation.

2. Development of smart and stimuli-responsive formulations[74]

An emerging trend in emulgel design involves the use of stimuli-responsive materials that react to physiological triggers such as temperature, pH, enzymatic activity, or oxidative stress. Thermoresponsive gels, for instance, undergo phase transitions at skin temperature, promoting prolonged retention and controlled drug release. These intelligent delivery systems are expected to enhance therapeutic efficiency and reduce dosing frequency.

3. Customization for personalized medicine[75]

The future of emulgel therapy may align with personalized medicine approaches, wherein formulations are adapted based on individual patient factors including skin physiology, genetic predisposition, and disease severity. Such customization would optimize therapeutic outcomes and reduce the risk of adverse effects, particularly in patients with hypersensitive or compromised skin barriers.

4. Use of natural and biocompatible excipients[76]

There is increasing emphasis on incorporating natural, biodegradable, and biocompatible excipients in emulgel formulations. Plant-derived polymers (e.g., xanthan gum, alginate), phospholipids (e.g., lecithin), and essential oils may serve as functional gelling agents, emulsifiers, or penetration enhancers. These components not only improve safety profiles but also align with regulatory trends toward sustainable and “green” pharmaceutical products.

5. Multifunctional and combination therapeutics[77]

Next-generation emulgels may be designed to co-deliver multiple active pharmaceutical ingredients (APIs), offering anti-inflammatory, antimicrobial, and antioxidant properties in a single formulation. This synergistic approach is particularly beneficial for complex skin conditions involving both inflammation and infection, thereby minimizing the need for multiple medications and improving adherence.

6. Expansion into transdermal delivery technologies[78]

Combining emulgels with advanced transdermal systems—such as microneedles, iontophoresis, or ultrasound-mediated delivery—could enhance drug absorption beyond the epidermal layer and facilitate systemic effects. This innovation may broaden the applicability of emulgels from purely topical treatments to systemic management of inflammatory conditions.

7. Industrial-scale production and manufacturing optimization[79]

For successful commercial translation, there is a need to refine large-scale manufacturing processes that ensure consistency, cost-effectiveness, and quality assurance. Techniques such as continuous processing, high-pressure homogenization, and real-time monitoring (PAT tools) will be vital for overcoming scalability and reproducibility challenges.

8. Regulatory standardization and quality assessment[80]

As emulgel-based drug products gain popularity, regulatory bodies are anticipated to establish dedicated guidelines concerning their evaluation. These would include standardized protocols for assessing physicochemical properties, drug release kinetics, microbiological stability, and dermal safety. Regulatory harmonization will facilitate smoother product approval and market penetration.

9. Clinical validation and long-term safety monitoring[81]

Robust clinical trials will be essential to establish the safety, efficacy, and acceptability of novel anti-inflammatory emulgels in human populations. Additionally, real-world evidence and pharmacovigilance data will contribute to post-marketing surveillance, enabling early detection of rare adverse events and supporting long-term therapeutic use.

CONCLUSION

Anti-inflammatory emulgels represent a valuable advancement in topical drug delivery, combining the structural advantages of both emulsions and gels. This biphasic system enhances percutaneous absorption, extends drug retention at the site of application, and promotes user acceptability due to their non-oily texture and ease of application. Recent progress—particularly the incorporation of nanotechnology, stimuli-responsive systems, and plant-derived actives—has broadened their applicability in treating both acute and chronic inflammatory disorders. However, critical challenges remain, including issues of physicochemical stability, precise drug release modulation, scalability in manufacturing, and the lack of standardized regulatory guidelines. Future directions are likely to focus on the development of patient-tailored, multifunctional emulgels with improved safety, efficacy, and compliance. The integration of advanced formulation strategies and clinical validation will be essential to support their transition from experimental preparations to widely accepted therapeutic options in dermatology and inflammatory disease management. Anti-inflammatory emulgels offer an innovative and efficient approach for topical drug delivery by combining the benefits of both emulsions and gels. This formulation enhances drug stability, improves skin absorption, and increases patient acceptability. By enabling targeted and sustained release of anti-inflammatory agents, emulgels provide effective treatment with reduced systemic exposure and side effects. Advances in nanoemulgel technology further refine drug delivery and therapeutic outcomes, making these formulations highly suitable for treating various inflammatory disorders. Ongoing research is likely to expand their use and improve treatment options in dermatology and related fields.

REFERENCES

1. Sreevidya VS. An overview on emulgel. Int J Pharm Phytopharmacol Res. 2019 Feb;:94.
2. Priyanka D, Sindhu S, Maanvizhi S. Design, development and evaluation of ibuprofen loaded nanosponges for topical application. Int J ChemTech Res. 2018;11(2):218-27.
3. Patel BM, Kuchekar AB, Pawar SR. Emulgel approach to formulation development. Biosci Biotechnol Res Asia. 2021 Sep;:460.
4. Kumar S, Singh N, Arora SC. Emulgel: an insight. Eur J Pharm Med Res. 2015;2(4):1168-86.
5. Upadhyaya S, Chauhan B, Kothiyal P. Emulgel: a novel approach for topical delivery of hydrophobic drugs. Int J Univ Pharm Bio Sci. 2014;3(2):176-89.
6. Joshi B, Singh G, Rana AC, Saini S, Singla V. Emulgel: a comprehensive review on the recent advances in topical drug delivery. Int Res J Pharm. 2011;2(11):66-70.
7. Pathan IB, Setty CM. Chemical penetration enhancers for transdermal drug delivery systems. Trop J Pharm Res. 2009;8:173-9.
8. Vats S, Saxena C, Easwari T, Shukla V. Emulsion based gel technique: novel approach for enhancing topical drug delivery of hydrophobic drugs. Int J Pharm Sci Res. 2014;3:2277-7873.
9. Dhawas V, Dhabarde D, Patil S. Emulgel: a comprehensive review for novel topical drug delivery system. Int J Recent Sci Res. 2020;11(4):38134-8.
10. Lakshmi SS, Divya R, Rao SY, Kumari KP, Deepthi K. Emulgel - novel trend in topical drug delivery system - review article. Res J Pharm Technol. 2021;14(5):2903-6.
11. Charyulu NR, Joshi P, Dubey A, Shetty A. Emulgel: a boon for enhanced topical drug delivery. J Young Pharm. 2021;13(1):76-9.
12. Abdo JM, Sopko NA, Milner SM. The applied anatomy of human skin: a model for regeneration. Wound Med. 2020;28:1-28.
13. Sabalingam S, Siriwardhene M. A review on emerging applications of emulgel as topical drug delivery system. World J Adv Res Rev. 2022;13(1):452-63.
14. Oseni BA, Osekita ST, Ibrahim MB, Igbokwe NH, Azubuike CP. Development of emulgel formulation from Markhamia tomentosa leaf extract: characterization and in-vitro antimicrobial activity against skin isolates. Am J Pharmacother Pharm Sci. 2024;3(9):1-9.
15. Rana A, Kumar A, Rana A, Sharma N, Chaudhary K, Gill NS. Formulation and evaluation of liquorice emulgel for topical drug delivery. World J Pharm Res. 2024;17:590-609.
16. Sushma G, Pravalika T, Sri BR, Priyanka P, Priya PV, Sharma JV. Emulgels - a novel approach for topical drug delivery. Int J Pharm Sci Rev Res. 2021;67:142-7.
17. Khare S, Abyankar S, Kuchekar A, Gawade A. A mini review - pharmaceutical creams. Scholars Acad J Pharm. 2021;10:60-2.
18. Lotfollahi Z. The anatomy, physiology and function of all skin layers and the impact of ageing on the skin. Wound Pract Res. 2024;32(1):6-10.
19. Hasan S, Bhandari S, Sharma A, Garg P. Emulgel: a review. Asian J Pharm Res. 2021;11(4):263-8.
20. Pawbake GR, Shirolkar SV. Microemulgel: a promising approach to improve the therapeutic efficacy of drug. J Crit Rev. 2020;7(14):1138-42.
21. John D, Charyulu RN, Ravi GS, Jose J. Nanosponge based hydrogels of Etodolac for topical delivery. Res J Pharm Technol. 2020;13(8):3887-92.
22. Sharadha M, Gowda DV, Gupta NV, Akhila AR. An overview on topical drug delivery system–updated review. Int J Res Pharm Sci. 2020;9(1):368-85.
23. Sabalingam S, Siriwardhene MA. A review on emerging applications of emulgel as topical drug delivery system. World J Adv Res Rev. 2022;13(1):452-63.
24. Hasan S, Bhandari S, Sharma A, Garg P. Emulgel: A review. Asian J Pharm Res. 2021;11(4):263-8.
25. Kalayni M, Yegen G, Ustundag Okur N, Aksu B. Evaluation of emulgel formulations containing diclofenac sodium via quality by design approach. J Res Pharm. 2022;26(3):460-8.
26. Isaac JA, Daburi A, Ifeanyi B, Ben-Umeh KC, Adedokun AA. Sennapodocarpa Emulgel: An herbal alternative for chemical burn wound treatment. Pharm Fronts. 2022;1:30-9.
27. Kumar Bandhu Lathiyare, Preeti KS, Vishal J. Development and in vitro characterization of piroxicam loaded emulgel for topical delivery. Int J Pharm Pharm Res. 2015;2(3):19-32.
28. Souza DZ, Rajashree G. Formulation: Design, development and evaluation of emulgel for topical delivery of meloxicam in the treatment of rheumatoid arthritis. Indo Am J Pharm Res. 2015;5(3):1721-9.
29. Hosny KM, Rambo SM, Al-Zahrani MM, Al-Subhi SM, Fahmy UA. Ketoprofen emulgel: Preparation, characterization, and pharmacodynamic evaluation. Int J Pharm Sci Rev Res. 2013;20(2):306-10.
30. Rana N, Singh V, Ali M. Formulation and characterization of ginger oil loaded polyherbal emulgels having extracts of Nardostachys jatamansi, Andrographis paniculata and Celaestrus paniculatus. Res J Pharm Technol. 2020;9:4077-83.
31. Khanapure MP, Bhosale DS, Kalyani N, Hotkar K. Formulation and evaluation of emulgel containing Piper nigrum and Curcuma longa extract for vitiligo. 2021;12(2):9283-93.
32. Milutinov J, Krstonosic V, Cirin D, Pavlovic N. Emulgels: Promising carrier systems for food ingredients and drugs. Polymers. 2023;15(10):2302.
33. Chauhan SB. Formulation and evaluation of emulgel for the treatment of acne. Res J Pharm Technol. 2020;8:3598-602.
34. Patel BM, Kuchekar AB, Pawar SR. Emulgel approach to formulation development: A review. Biosci Biotechnol Res Asia. 2021;3:459-65.
35. Bhavyashree T, Bhute S, Alva SH, Shubhashree AS, Spoorthi C, Rai S, Shabaraya AR. Emulgel: An effective approach for the topical drug delivery. J Xi’an Shiyou Univ. 2021;10:593-603.
36. Jain NK. Progress in controlled and novel drug delivery systems. New Delhi: CBS Publishers and Distributors; 2004. p. 319-20.
37. Hardenia A, Jayronia S, Jain S. Emulgel: An emergent tool in topical drug delivery. Int J Pharm Sci Res. 2014;5:1653-60.
38. Kumar S. Formulation and evaluation of metronidazole emulgel for topical drug delivery. J Pharm Negative Results. 2022;13(9):10493-509.
39. Khan BA, Ahmad S, Khan MK, Hosny KM, Bukhary DM, Iqbal H, et al. Fabrication and characterization of pharmaceutical emulgel co-loaded with naproxen-eugenol for improved analgesic and anti-inflammatory effects. 2022;8(10):608.
40. Shehata TM, Nair AB, Dhubiab BE, Shah J, Jacob S, Alhaider IA, et al. Vesicular emulgel based system for transdermal delivery of insulin: Factorial design and in-vivo evaluation. Appl Sci. 2020;15:5341-6.
41. Light K, Karboune S. Emulsion, hydrogel and emulgel systems and novel applications in cannabinoid delivery: A review. Crit Rev Food Sci Nutr. 2022;29:8199-229.
42. Demina TS, Birdibekova AV, Svidchenko EA, Ivanov PL, Kuryanova AS, Kurkin TS, et al. Solid-state synthesis of water-soluble chitosan-g-hydroxyethyl cellulose copolymers. Polymers. 2020;3:611-5.
43. Devi A, Yadav R, Bhateja P, Piplani M. A systematic review on emulgel. IJPSR. 2025;16(8):2218.
44. Malavi S, Kumbhar P, Manjappa A, Disouza J, Dwivedi J. Emulgel for improved topical delivery of tretinoin: Formulation design and characterization. Ann Pharm Fr. 2022;80(2):157-68.
45. Breitkreutz D, Mirancea N, Nischt R. Basement membrane in skin: Unique matrix structure with diverse functions. Histochem Cell Biol. 2009;132(1):1-10.
46. Iozzo RV. Basement membrane proteoglycans: From cellar to ceiling. Nat Rev Mol Cell Biol. 2005;6(8):646-56.
47. Proksch E, Brandner JM, Jensen JM. The skin: An indispensable barrier. Exp Dermatol. 2008;17(12):1063-72.
48. Rani J, Rode M, Ali M, Dolas J, Khedade K, Dixit G. Formulation and evaluation of emulgel using miswak oil for the management of inflammation: Research paper. Int J Multidiscip Res. 2024;7(July–August).
49. Zotova N, Zhuravleva Y, Chereshnev V, Gusev E. Acute and chronic systemic inflammation: Features and differences in the pathogenesis, and integral criteria for verification and differentiation. Int J Mol Sci. 2023;24(2):1144.
50. Sah S, Badola A, Nayak B. Emulgel: Magnifying the application of topical drug delivery. Indian J Pharm Biol Res. 2017;5(1):25–30.
51. Ajazuddin, Alexander A, Khichariya A, Gupta S, Patel RJ, Giri TK, Tripathi DK. Recent expansions in an emergent novel drug delivery technology: Emulgel. J Control Release. 2013 Oct 28;171(2):122-32.
52. Singh S, Singh I. Evolving implementation of emulgel as a topical drug delivery system: A systematic review. Curr Res Pharm Sci. 2022;12(3):121-31.
53. Kudipudi SA, Korni RD, Putta S, Niharika VVS, Kinnera S, Lakshmi SVVNS. A review on emulgel: Focus on reported research works of synthetic and herbal drugs. J Chem Health Risks. 2024; [page no. 405].
54. Lal DK, Kumar B, Saeedan AS, Ansari MN. An overview of nanoemulgels for bioavailability enhancement in inflammatory conditions via topical delivery. Pharmaceutics. 2023;15(4):1187.
55. EP4294418A1 – Novel arthritis emulgel composition and its preparation process [patent].
56. Chen Y, Lee JH, Meng M, Cui N, Dai CY, Jia Q, Lee ES, Jiang HB. An overview on thermosensitive oral gel based on poloxamer 407. Materials. 2021;14(16):4522.
57. Rainsford KD. Anti-inflammatory drugs in the 21st century. Subcell Biochem. 2009;49:3–27.
58. Barnes PJ. Mechanisms and resistance in glucocorticoid control of inflammation. J Steroid Biochem Mol Biol. 2011;120(2-3):76–85.
59. Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016;388(10055):2023–38.
60. Bertolini A, Ferrari A, Ottani A, Guerzoni S, Tacchi R, Leone S. Paracetamol: New vistas of an old drug. CNS Drug Rev. 2006;12(3-4):250–75.
61. Gibson AL, Lovell MA. Topical NSAIDs in the treatment of osteoarthritis. Clin Pharmacol Ther. 2017;102(6):1001–11.
62. Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol. 2009;41(1):40–59.
63. Calder PC. Omega-3 fatty acids and inflammatory processes: from molecules to man. Biochem Soc Trans. 2017;45(5):1105–15.
64. Petersen AMW, Pedersen BK. The anti-inflammatory effect of exercise. J Appl Physiol. 2005;98(4):1154–62.
65. Black PH. The inflammatory response is an integral part of the stress response: Implications for atherosclerosis, insulin resistance, type II diabetes and metabolic syndrome X. Brain Behav Immun. 2006;20(2):148–54.
66. Kumari P, Ghosh B, Biswas S. Nanocarriers for cancer-targeted drug delivery. J Drug Target. 2016;24(4):263–80.
67. Bhatia S, Ponnazhagan S. Gene therapy approaches to target inflammation and autoimmune diseases. Clin Immunol. 2018;188:47–53.
68. Honda K, Littman DR. The microbiome in infectious disease and inflammation. Annu Rev Immunol. 2016;34:249–76.
69. Abdel-Mottaleb N, Eldin MS, El-Mahdy M, El-Bary AA. Topical posaconazole emulgel for the treatment of fungal skin infections: Formulation, characterization, and in vivo evaluation. Drug Dev Ind Pharm. 2021;47(9):1452–61.
70. Pandey SK, Singh PK, Tripathi DK. Nanoemulsion-based emulgel for topical delivery of hydrophobic drugs: formulation development and evaluation. Int J Pharm. 2020;579:119156.
71. Kumar MR, Sharma P, Reddy GV. Effect of excipients on the rheological and permeation properties of topical emulgels: a systematic review. J Control Release. 2022;341:230–45.
72. Silva JA, Almeida LP, Santos VC. Patient-centric topical formulations: Emulgels as promising carriers for dermatological disorders. Clin Ther. 2021;43(7):1225–36.
73. Singh S, Kaur M, Nagpal K, Singh SK, Sharma N, Singh R. Nanoemulsion based drug delivery system: recent advances and future prospects. Drug Deliv. 2020;27(1):230–43.
74. Mahmoud MN, El Gendy NA, Elsayed AA, Fetih GN, Zekry IA. Biodegradable ingredient based emulgel loaded with ketoprofen nanoparticles. AAPS PharmSciTech. 2018;19(8):3438–49.
75. Lal DK, Kumar B, Saeedan AS, Ansari MN. An overview of nanoemulgels for bioavailability enhancement in inflammatory conditions via topical delivery. Pharmaceutics. 2023;15(4):1187.
76. Bashir S, Tandel K, Ramaswamy V, et al. Nanoemulgel, an innovative carrier for diflunisal topical delivery with profound anti-inflammatory effect: in vitro and in vivo evaluation. Drug Dev Ind Pharm. 2021;47(5):735–49.
77. Development, characterization and optimization of the anti-inflammatory influence of meloxicam loaded into a eucalyptus oil based nanoemulgel. ACS Omega. 2022;7(17):14592–603.
78. Khan BA, Ahmad S, Khan MK, Hosny KM, Bukhary DM, Iqbal H, et al. Fabrication and characterizations of pharmaceutical emulgel co-loaded with naproxen eugenol for improved analgesic and anti-inflammatory effects. Gels. 2022;8(10):608.
79. Enhancement of curcumin anti-inflammatory effect via formulation into myrrh oil based nanoemulgel. Polymers. 2021;13(4):577.
80. Emulgels containing propolis and curcumin: The effect of type of vegetable oil, poly(acrylic acid) and bioactive agent on physicochemical stability, mechanical and rheological properties. Gels. 2021;7(3):120.
81. Development of celecoxib emulgel by using natural oil. J Pharm Investig. 2023. Article no: e-pub ahead of print.
82. Development of Vitis vinifera nanoemulgel and evaluation of its potential anticancer, antimicrobial and anti-inflammatory effects. BMC Complement Med Ther. 2025;25(1):148.