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Abstract

Nanoemulgels represent an innovative drug delivery system combining the benefits of nanoemulsions and hydrogels for enhanced topical and transdermal applications. By integrating nanoemulsions into a gel matrix, Nanoemulgel offer improved drug solubility, stability, and targeted delivery, ensuring better therapeutic outcomes. This review focuses on the formulation, evaluation, and applications of nanoemulgels in treating various skin disorders, including seborrheic dermatitis, psoriasis, fungal infections, and acne. Their advantages, such as controlled drug release, improved skin permeability, and patient compliance, make them a promising platform for delivering both hydrophilic and lipophilic drugs. Additionally, nanoemulgels find applications in cosmetics, wound healing, and veterinary medicine, showcasing their versatility. Through this comprehensive exploration, the study highlights the potential of nanoemulgels to revolutionize topical drug delivery and address the limitations of conventional formulations.

Keywords

Nanoemulsion, nanoemulgel, topical drug delivery system, skin infections, etc

Introduction

Emulgel:

Emulgel is a combination of gel and emulsion where emulsion used can be both type W/O and O/W as a vehicle for purpose to deliver selected drug to the skin. Water Phase containing the gelling agent converts a classic emulsion in emulgel. Dermatological use of Emulgel has many favourable properties like easy spreadable, greaseless, being thixotropic, water-soluble, easy removal, longer shelf life, non-staining, and bio-friendly.

Drugs can penetrate into the skin structure:

a. through thick stratum corneum, (SC)

b. Sebaceous follicle.

c. sweat ducts of skin, Stratum corneum covers more than 99% of skin available for drugs to be absorbed. Passing through this is the rate limiting step for drug percutaneous absorption. Establishment of a concentration gradient thought to be major steps involved in percutaneous absorption, which provides force necessary for drug adsorption across the skin.

Nanoemulsion:

For most medicines, the nanoemulsion method is an ideal drug delivery to optimize effectiveness while reducing toxicity. Researchers have excogitated the simple delivery of drugs in advancing research into eminently refined novel dosage forms. Nanoemulsion system consists of combining nano ranges of two immiscible liquids (water and oil) to form a homogeneous solution by adding appropriate surfactants/cosurfactants with an acceptable HLB value. This stable, thermodynamic system ranges from 10-100 nm. Figure 1 describes the various compartments of a nanoemulsion that has been stabilized. Nanoemulsion is a promising option for enhancing the penetration of the drug delivery system and targeting poorly soluble drugs by increasing their absorption through the skin, improving drug processing time in the target area and eventually leading to less side effect. The effects of nanoemulsion with globules in an emulsion's nano-scale size do not transmit on the physical properties of the emulsion itself. Yet, the bioavailability of therapeutic drugs as a whole was encountered. Also, Nanoemulsion improves drug permeation across the skin, which interacts with researchers' interests. Moreover, the small size of particles, the more medication can be introduced into the mixture, which then enhances the thermodynamics towards the skin. The drug-affinity for partitioning enhances skin permeation. The greatest obstacle upon transdermal drug delivery refers to barrier properties of the stratum corneum a 10 µm to 20µm thick tissue layer with a great composed, structured lipid/protein matrix. A recent study, of topical delivery lipophilic flurbiprofen in nanoemulsion proves an increase in bioavailability by 4.4 times compared to oral administration. Hence, the nanoemulsion as a spontaneous emulsifying method which provides numerous advantages over another carrier such as polymeric nanoparticle and liposomes, including low cost preparation procedure, high hydrophilic and lipophilic drug loading system to enhance the longer shelf lives upon preserving the therapeutic agents.

       
            1.png
       

Nanoemulgel:

Nanoemulgel, which known as the formation of nanoemulsion based on hydrogel is the addition of the nanoemulsion system intergraded into the hydrogel matrix which influences better skin penetration. This mixture of nanomulgel has attracted the attention of many scientists for the development of numerous drugs that function to treat various kinds of skin disorders. Emulgel is not a new type of formulation and is already present in the market. The formulation of nanoemulgel for the topical delivery system acts as drug reservoirs which, influence the release of drugs from the inner stage to the outer phase and then further onto the skin. These release mechanisms depend on the composition of the network polymer chains and the crosslink density. Besides that, the ability of a drug to permeate the skin and successfully release of the therapeutic agent is influenced by drug affinity to diffuse out from the vehicle and permeate through the barrier. Nanoemulgel on intact with skin will release the oil droplets from the gel network. The oil droplets then will penetrate the stratum corneum of the skin and directly deliver the drug molecules without a transfer via the hydrophilic phase of nanoemulsions.(1–4)

  • Structure of Skin:
  • Skin is the largest organ of the body, accounting for about 15% of the total adult body weight.
  • Weight of skin is about 4kg.
  • Thickness 0.5 to 3mm.
  • It protects against external factors like physical, chemical.
  • It prevents excessive water loss from the body.
  • It helps in thermoregulation.

       
            2.jpg
       

Skin is composed of three main layers are as follows,

a. Epidermis

b. Dermis

c. Hypodermis

a. Epidermis:

  • Epidermis is the outermost layer of the skin.
  • It is made of keratinized stratified squamous epithelial cells.
  • It forms the waterproof, protective wrap over the body’s surface which also serve as a barrier to infection.
  • Thickness of epidermis depending on cell size and number of cell layers.

       
            3.jpg
       

b. Dermis/Cornium:

  • Dermis is the layer of the skin beneath the epidermis, that consist of epithelial tissue.
  • Protect the body from stress and strain.
  • Dermis is located between epidermis and hypodermis.
  • Dermis is tightly connected to the epidermis by a base membrane.
  • There are two layers of dermis:
  1. Papillary layer     b) Reticular layer

       
            4.jpg
       

 c. Hypodermis/Subcutaneous layer:

  • Hypodermis is the bottom layer of skin.
  • Hypodermis lies below the dermis.
  • It is also known as subcutaneous tissue.
  • It is made up of fats and adipose tissue.
  • It is reduced by cosmetic liposuction(lipoplasty).
  • Functions as energy source by storing fat.(1,5)

       
            5.jpg
       

  Drug Delivery Through Skin :

Stratum Corneum of the skin acts as a powerful water barrier and protects deep inner structures and blood vesicles which are distributed below the skin. Especially continuous venous plexus which is supplied by flow of blood from the skin’s blood capillaries is more important. More exposed areas like feet and hands; blood is also supplied directly through small arteries from highly muscular arteriovenous anastomoses. The skin prevents absorption along with loss of electrolytes and water. Passing from this barrier and getting absorbed in to skin layers, drug has to go through one of these channels; intercellular, transcellular, and follicular. But follicular route also known as shunt pathway found controversial in many study so mainly other two are considered as main mechanism of drug absorption. Intercellular route thought to be predominating for most drugs compare to transcellular where drug has to absorb through several of lipophilic and hydrophilic differential skin layers.(1)

  • Function of Skin:
  • Protection against microorganisms, UV-light and mechanical damages.
  • Prevents excessive water loss(Homeostasis).
  • Production of Vitamin-D.
  • Secretion of Vitamin-E.
  • Helps in thermoregulation.
  • Acts as a sensory organs(touch, defects, temperature).
  • Protects internal structure.
  • Absorption
  • Problems related to the Skin :

Nanoemulgels have been extensively researched and developed for the treatment of various skin-related conditions due to their enhanced penetration, controlled drug release, and improved therapeutic efficacy.

  • Types of skin:
  1. Oily skin:
  • Oily skin have large pores, shiny complexation, blackheads, pimples by sebaceous glands.
  • Oiliness of skin can be increased by factors like stress, hormones, heat and humidity.

2.   Combination skin:

  • It is only in some areas like chin, nose, forehead but may be dry in some areas like cheeks.
  1. Normal skin:
  • It has medium level of oil and water.
  • Not shiny or oily because oil glands are not highly active.

4.   Sensitive skin :

  • It show redness, itching and dryness.
  • Can be irritated in response to certain skin care products.

Below are some key skin problems that can be effectively managed using nanoemulgels:v

1. Fungal Infections

  • Examples: Seborrehic Dermatitis, Athlete’s foot (tinea pedis), ringworm (tinea corporis), and candidiasis.
  • Rationale: Nanoemulgels enhance the solubility and penetration of antifungal drugs like Ketoconazole, Posaconazole or Clotrimazole, ensuring better skin permeation and targeting of fungal colonies in deeper layers of the skin.(6)

       
            Seborrheic Dermatitis.jpg
       

Seborrheic Dermatitis

2. Bacterial Infections

  • Examples: Impetigo, cellulitis, and folliculitis.
  • Rationale: Nanoemulgels deliver antibacterial agents like Mupirocin or Clindamycin directly to the site of infection, improving localized drug concentration while minimizing systemic exposure and side effects.

       
            Impetigo.jpg
       

Impetigo

3. Acne Vulgaris

  • Rationale: Nanoemulgels containing drugs like Clindamycin, Adapalene, or Salicylic Acid enhance the penetration into sebaceous glands, providing anti-inflammatory, keratolytic, and antimicrobial effects, while reducing irritation associated with traditional formulations.

       
            Acne Vulgaris.jpg
       

Acne Vulgaris

4. Psoriasis

  • Rationale: For chronic skin conditions like psoriasis, nanoemulgels improve the delivery of drugs like Tacrolimus or Calcipotriol, enhancing skin hydration, reducing scaling, and ensuring sustained drug release for prolonged therapeutic effects.

       
            Psoriasis.jpg
       

Psoriasis

5. Eczema and Dermatitis

  • Examples: Atopic dermatitis and contact dermatitis.
  • Rationale: Nanoemulgels with corticosteroids (e.g., Hydrocortisone) or immunomodulators reduce inflammation, redness, and itching, with better skin retention and reduced systemic absorption.

       
            Eczema and Dermatitis.jpg
       

Eczema and Dermatitis

6. Hyperpigmentation Disorders

Hyperpigmentation means that the skin looks darker than the normal skin(often brown to grey).

  • Examples: Melasma, freckles, and post-inflammatory hyperpigmentation.
  • Rationale: Nanoemulgels enhance the delivery of depigmenting agents like Hydroquinone, Kojic Acid, or Arbutin, promoting even skin tone and better efficacy.

       
            Hyperpigmentation.jpg
       

Hyperpigmentation

7. Burns and Wound Healing

  • Rationale: Nanoemulgels incorporating agents like Silver Sulfadiazine or herbal extracts (e.g., Curcumin or Aloe Vera) enhance antimicrobial action, promote faster healing, and maintain hydration in burn wounds or chronic ulcers.

       
            Burns.jpg
       

Burns

8. Pain and Inflammation

  • Examples: Localized skin pain or inflammation due to injury or conditions like rosacea.
  • Rationale: Nanoemulgels formulated with Diclofenac or Ibuprofen offer targeted anti-inflammatory effects, reducing swelling and pain.

9. Skin Cancer

  • Examples: Basal cell carcinoma or melanoma (topical adjunct therapy).
  • Rationale: Nanoemulgels delivering drugs like 5-Fluorouracil or Imiquimod enhance penetration and local drug action while minimizing systemic toxicity.

       
            Melanoma.jpg
       

Melanoma

10. Skin Aging (Cosmetic Applications)

  • Rationale: Nanoemulgels with antioxidants (e.g., Vitamin C, Retinoids, or Coenzyme Q10) reduce wrinkles, improve elasticity, and provide hydration, making them effective for anti-aging treatments.

       
            Aging.jpg
       

Aging

11. Viral Skin Infections

  • Examples: Herpes simplex and warts.
  • Rationale: Nanoemulgels enhance the localized delivery of antiviral drugs like Acyclovir, reducing lesion duration and recurrence.

       
            Herpes Simplex.jpg
       

Herpes Simplex

Nanoemulgels are a versatile and promising approach for the treatment of these and other skin conditions, offering enhanced drug delivery, improved patient compliance, and better therapeutic outcomes.(6,7)

  • Objectives:
  1. Primary objective of nanoemulgel is to develop drug loaded emulgel.
  2. To find out is the drug compatible with excipients in emulgel for the patients.
  3. Characterization of the drug including various physicochemical characterization.
  4. To improve the patients compliance.
  • Advantages of Nanoemulgel:
  1. It is safe on Transdermal application due to its non-toxic nature.
  2. Stability of Nanoemulsion is enhanced due to distribution of oil droplets in Gel base; where affinity of the drug toward oil determines stability.
  3. Also good adhesion on the skin with high solubilising power leads to high concentration gradient that increase penetration of drug as it moves down.
  4. Moreover, these types of formulation give support to delivery of lipophilic and poorly water soluble drugs and also improve patient compliance.
  5. Nanoemulgel also helps in controlled release of drugs having the shorter half-life. e. Provide higher Spread-ability of the formulation than creams.
  6. Nanoemulgel are Non toxic and non irritant.
  7. Better loading of drug compare to other formulation.
  8. Increase skin permeability and drug deposition.
  9. Non-greasy and easy to apply, improving patient compliance.
  10. Avoidance of first-pass metabolism and systemic side effects.(5)
  • Disadvantages of Nanoemulgel:
  1. Low viscosity and spreadability
  2. Less permeability and bioavailability of drug
  3. Non-compatibility and skin irritability
  4. Possibility of allergic reactions
  5. Bubbles formed during emulgel formulation.(5)
  • Factors Affecting Topical Absorption of Drug :

A. Physiological factors:

    1. Lipid content of the skin - act as barrier for drug absorption and lowering this barrier property leads to increased penetration.
    2. Thickness of different skin layers -Greater the thickness lower the penetration rate, like palm and sole shows higher diffusion rate compare to other surfaces.
    3. Hair follicles density - large storage, about 10-12 times than SC.
    4. Skin pH.
    5. Hydration of skin.
    6. Sweat gland density.
    7. Inflammation of skin disrupted stratum corneum has higher permeability.
    8. Blood flow.
    9. Skin temperature

B. Physicochemical:

    1. Partition coefficient - higher log p value give rise to absorption.
    2. Effect of vehicles - hydro alcoholic gel provides the most efficient absorption through skin.
    3. Degree of ionisation.
    4. Molecular Weight. (less than 400 Dalton).(5)
  • Component of Nanoemulgel:

Components

Examples

Oil

Castor oil., ethyl oleate., sesame oil., Arachis oil., lanolinCapryol 90., isopropyl myristate., olive oil., oleic acid., isopropyl palmitate., corn oil.

Surfactants

Nonionic - Fatty alcohols, Glycerol esters, Fatty acid esters. Anionic contain - Carboxylate groups, Soaps, Sulfonates, Divalent ions Cationic- Amines and quaternary ammonium compounds. Zwitterionic surfactants-phospholipids

Co-surfactants

Propylene glycol., glycerine., Lecithin., Propanolol., Transcutol P., Ethanol., Polyethylene glycol Butanol

Gelling Agent

Collagen., Agar., Tragacanth., Guar gum., Gelatin., HPMC., Carbopol934.,940.,941

Penetration Enhancers

Alcohols., Polyols., Alkanes., Ester., Terpenes., Surface active agent

Preservatives

methylparaben, Propyl paraben, Benzalkonium chloride, and phenoxyethanol

Anti-oxidants

Ascorbyl palmitate, Butylated hydroxytoluene, etc.

pH Modifiers

Triethanolamine.

a. Oils: Oils used in Nanoemulsion are generally mineral oils used as the vehicle for drugs E.g. castor oils and various fixed oils (cottonseed oil, maize oils, arachisoil ) Olive Oil, Coconut Oil, eucalyptus oil, rose oil, clove oil etc.

b. Aqueous Phase: Commonly distilled water is used as a aqueous phase for the preparation of Nanomulsion and hydrogel.

c. Surfactant and Co-Surfactant: Surfactants are used both to give emulsification at the time of formulation and control day to day stability during shelf life of prepared Nanoemulsion. General selection of surfactant depends on the type of emulsion. (O/W or W/O) E.g. Span 80 (Sorbitanmonooleate), Acrysol K 140, Polyethylene-glycol-40-stearate, Acrysol, Labrasol, Stearic acid, PlurolOleique, Tween 80 (Polyoxyethylene-sorbitan-monooleate), Labrafil, Sodium stearate, Where agents like Transcutol ,Captex, Cammul, Migyol, etc. can be use as co-surfactant or co-solvents.

d. Gelling Agent: Polymers essential to give the structural network for the preparation of gels are known as gelling agents E.g. Natural - Agar, Tragacanth, Guar gum, Xanthan Gum, Semi-synthetic and Synthetic Carbapol, Poloxamer, HPMC (cellulose derivatives)

e. Permeation Enhancers: They interact with different skin constituents to produce a reversible temporary increase in permeability. They can act by one or more mechanisms like,

i. Disrupting the highly compact structure of SC.

ii. Improving partition of drug or solvent or co-enhancer into the SC.

iii. Interacting intercellular protein. Causing conformational changes in protein or solvent swelling is the key for alternating polar path. Some enhancers improve the fluidity of protein in SC, where some act on both pathways by disrupting multilaminate pathway. They can increase the diffusion of drug through skin proteins. Type of enhancer has a significant impact product designing E.g. Eucalyptus oil, Linoleic acid, Lecithin, Oleic acid, Chenopodium oil, Isopropyl myristate, Urea.

f. Preservatives: Preservatives are chemical substances used to protect a substance from microbiological degradation and extend a product's shelf life. Preservatives including methylparaben, Propyl paraben, Benzalkonium chloride, and phenoxyethanol are frequently utilized.

g. Antioxidant: Antioxidants are chemical compounds used in compositions to prevent various components from oxidizing. For example, Ascorbyl palmitate, Butylated hydroxytoluene, etc.

h. pH modifiers: The pH value also indicated the stability of the nanoemulsion. The mean value of pH should lies in the range of 5.4 - 5.9 (pH of skin). Most commonly used pH modifier is Triethanolamine.(8)(9)

  • Methods of Preparation :
  1. Homogenization using high pressure: For the preparation of stabilized nanoemulsion with particle size 1 nm, the high-pressure homogenizer piston is used by applying several forces, such as cavitation, etc. This process will continue until a desired nanosize formulation was obtained.
  2. Microfluidization: Microfluidization of the prepared formulation is done by the use of a device known as microfluidizer. The use of high pressure forces the product into microchannels to get a submicron range particle. The process was repeated until a stabilized nanoemulsion was obtained.
  3. Ultrasonication: In the case of ultrasonication technique, ultrasonic vibrations are used to obtain stabilized nanoemulsion with reduced particle size. In this, cavitation is the preferred mechanism for obtaining desired nanosized formulation.
  4. Phase inversion method: A stabilized nanoemulsion is obtained using the phase inversion method which, with the aid of the emulsification process, endorses chemical energy for phase transition under constant temperature.
  5. Self-emulsifying gel method: This method involves the use of a self-emulsifying drug delivery system (SEDDS])that can create Nanoemul gel in situ. The SEDDS is a mixture of oil, surfactants, and co-solvents that can spontaneously emulsify when in contact with water. When the SEDDS is mixed with a hydrophilic gel matrix, a Nanoemul gel is formed.
  6. High-energy emulsification method: This method involves the use of high-energy input to create small droplets of the dispersed phase (oil) in the continuous phase (water). This can be achieved through various methods such as sonication, high-pressure homogenization, or microfluidization. The resulting emulsion can then be transformed into a gel by adding a gelling agent such as a polymer or a surfactant.
  7. Phase inversion temperature (PIT) method: This method involves the use of a thermosensitive surfactant that undergoes a phase transition from a water-soluble to a water-insoluble state at a certain temperature. By adjusting the temperature of the system, the surfactant can be induced to form a gel-like structure that entraps the dispersed phase.
  8. Sol-gel transition method: This method involves the use of a sol-gel transition system, where a gel is formed by the aggregation of a network of particles or polymers in a solvent. This can be achieved by adding a crosslinking agent or a thermosensitive polymer to the emulsion, which triggers the formation of a gel-like structure at a certain temperature or under certain conditions.
  9. Electrostatic complexation method: This method involves the use of oppositely charged polymers or surfactants to create a stable emulsion, which can then be transformed into a gel by adding a crosslinking agent or a gelling agent.
  10. Coacervation method: This method involves the use of two or more polymers that undergo phase separation in the presence of an electrolyte or a pH change, resulting in the formation of a gel-like structure. The dispersed phase can then be incorporated into the gel by high-energy emulsification or other methods.(8–10)
  • Evaluation of Nanoemulsion :

1. Appearance : The prepared nanoemulgel formulations were inspected visually for their colour, homogeneity, consistency and pH. The pH values of 0.1% aqueous solutions of the prepared Gellified Emulsion were measured by a pH meter.

Scanning Electron Microscopy : The morphology of nanoemulsion can be determined by scanning electron microscopy (SEM). SEM gives a three-dimensional image of the partical. The samples are examined at suitable accelerating voltage, usually 20 kV, at different magnifications. A good analysis of surface morphology of disperse phase in the formulation is obtained through SEM. Image analysis software, may be employed to obtain an automatic analysis result of the shape and surface morphology.

2. Particle Size Analysis : Formulated Nanoemulsion should be analysed for their hydrodynamic particle size. Generally, in case of nanoemulsion dynamic light scattering method used for the measurement of particles and further particle size distribution.

3. Zeta potential measurements : Zeta potential for nanoemulsion was determined using zetasizer hsa 3000 (Malvern instrument Ltd., UK). Samples were placed in clear disposable zeta cells and results were recorded. Before putting the fresh sample, cuvettes were washed with the methanol and rinsed using the sample to be measured before each experiment.

4. Entrapment efficiency : Entrapment efficiency is defined as the percentage amount of drug which is entrapped by the Nanoemulsion. For the determination of entrapment efficiency, the unentrappped drug was first separated by centrifugation at 15000 rpm for 30 minutes. The resulting solution was then separated and supernatants liquid was collected. The collected supernatants were then diluted appropriately with methanol and estimated using UV visible spectrophotometer at 261 nm.

5. Determination of drug content : An estimated 1 ml of nano-emulsion was dissolved in pH 6.4 phosphate buffer. The solution was then filtered and suitably diluted, and the resulting solution was analyzed at 226nm in the UV-visible Spectrophotometer.

6. Determination of percentage transmittance : To determine transparency, % transmittance was measured on a UV spectrophotometer. All nanoemulsion formulations were diluted 50 times with distilled water. Then the percent transmittance was measured at 650 nm in a UV spectrophotometer using distilled water as blank.

  • Evaluation of Nanoemulgel :

1. Determination of pH : pH of the formulation was determined by using digital pH meter. pH meter electrode was washed by distilled water and then dipped into formulation to measure pH and this process was repeated 3 times.

2. Measurement of viscosity : The viscosity of the formulated batches was determined using a Brookfield Viscometer (RVDV-I Prime, Brookfield Engineering Laboratories, USA) with spindle 63. The formulation whose viscosity was to be determined was added to the beaker and was allowed to settle down for 30 min at the assay temperature (25±1ºC) before the measurement was taken. Spindle was lowered perpendicular in to the centre of emulgel taking care that spindle does not touch bottom of the jar and rotated at a speed of 50 rpm for 10 min. The viscosity reading was noted.

3. Spreadability : To determine spreadability of the gel formulations, two glass slides of standard dimensions were selected. Formulation whose spreadability was to be determined was placed over one slide and the other slide was placed over its top such that the gel is sandwiched between the two slides. The slides were pressed upon each other so as to displace any air present and the adhering gel was wiped off. The two slides were placed onto a stand such that only the lower slide is held firm by the opposite fangs of the clamp allowing the upper slide to slip off freely by the force of weight tied to it. 20 gm weight was tied to the upper slide carefully. The time taken by the upper slide to completely detach from the lower slide was noted. The spreadability was calculated by using the following formula.

S = M. L/T

Where,

M = weight tied to upper slide,

L = length of glass slides,

T = time taken to separate the slides.

4. Drug content study : Drug content study was done to determine the amount of the drug present in the certain quantity of the formulation. Took 1 g of the formulation into 10 ml volumetric flask added methanol in it and shake well and make up the volume with methanol. The Volumetric flask was kept for 2 hr and shaken well in a shaker to mix it properly. The solution was passed through the filter paper and filtered the mixer then measured absorbance by using spectrophotometer at 261 nm.

5. In-vitro Drug release study : The in vitro drug release studies of the Emulgel were carried out on Diffusion cell using egg membrane. This was clamped carefully to one end of the hollow glass tube of dialysis cell. Emulgel (1gm) was applied on to the surface of egg membrane dialysis membrane. The receptor chamber was filled with freshly prepared PBS (pH 7.4) solution. Total amount of gel filled in the tube to solubilize the drug. The receptor chamber was stirred by magnetic stirrer. The samples (1ml aliquots) were collected at suitable time interval sample were analyzed for drug content by UV visible spectrophotometer at 261 nm after appropriate dilutions. Cumulative corrections were made to obtain the total amount of drug release at each time interval. The cumulative amount of drug release across the egg membrane was determined as a function of time. The cumulative % drug release was calculated using standard calibration curve.

6. Release kinetics of selected formulation : To examine the drug release kinetics and mechanism, the cumulative release data were fitted to models representing Zero order (cumulative % drug release v/s. time), First order (log cumulative % drug retained v/s. time), Higuchi model (cumulative % drug retained v/s. Square root of time).

7. Optimization Study : All experiments were performed in triplicates. All data are reported as mean ± standard deviation (SD) and the groups were compared using ANOVA, with p<0.05 considered statistically significant.

8. Zeta potential : The zeta potential of nanoemulsion was determined using nano zeta sizer Horiba scientific SZ-100.

9. Determination of percentage yield of nanoemulgel formulation : Weight of all ingredients used was added up theoretically. The percentage yield was calculate by the formula.

% yield = Practical yield/Theoretical yield×100

10. Swelling index : 1gm of prepared topical nanoemulgel is taken on porous aluminium foil which is then placed on 10ml of 0.1N NaOH solutions. Sample removed time to time and weight is noted till no further change in weight.

Swelling Index(SW)% = [(Wt-Wo)/Wo]100

Where,

(SW) %= Percentage swelling,

Wo= Original weight of nanoemulgel,

Wt=Weight of swollen nanoemulgel at time t.

11. Skin irritation test : 0.25gm nanoemulgel is applied to each different site(two sites/rabbit). After 24hr of application rabbit skin site are wiped and cleaned, change in colour of skin or undesirable change in morphology is noted and checked.

12. Stability studies : The prepared nanoemulgel formulations were stored away from light in a collapsible tube at 25±2°C, 40±2°C and 4±2°C for three months. After storage, the samples were tested for their physical appearance, pH, rheological behavior, drug release.

13. Excrudability studies (tube test): This test was used to measure the force required to extrude the material from the tube. The evaluation of extrudability was based upon the quantity of nanoemulgel extruded from the lacquered aluminum collapsible tube on the application of weight in grams required to eject at least 0.5cm ribbon of nanoemulgel in 10 seconds [17]. The better extrudability is depended upon the quantity ejected. The extrudability is than calculated by using the following formula,(8,11,12)

Excrudability = Applied weight to excrude nanoemulgel from the tube (in/g)/Area (in cm2).

  • Application of Nanoemulgel:
  1. Topical Drug Delivery: Treats skin conditions like seborrheic dermatitis, psoriasis, acne, and fungal infections.
  2. Transdermal Drug Delivery: Enables systemic drug delivery, bypassing first-pass metabolism.
  3. Cosmetic Use: Used in moisturizers, anti-aging creams, sunscreens, and skin-lightening products.
  4. Antifungal Agents: Effective for treating fungal infections such as candidiasis and ringworm.
  5. Anti-inflammatory Drugs: Localized delivery of NSAIDs for pain and inflammation.
  6. Wound Healing: Promotes healing with bioactive or antimicrobial agents.
  7. Antimicrobial Delivery: Treats bacterial infections and acne.
  8. Ocular Delivery: Improves bioavailability for eye treatments like conjunctivitis.
  9. Veterinary Use: Treats skin infections and wounds in animals.
  10. Herbal Delivery: Enhances stability and effectiveness of herbal actives (e.g., curcumin, neem oil).
  11. Cancer Therapy: Localized delivery for skin cancer treatments.
  12. Personal Care: Used in deodorants, shaving gels, and lip care products.

Nanoemulgels are versatile, offering enhanced drug delivery, stability, and patient compliance across various fields.(13)

  • CONCLUSION:

Topical Nanoemulgels have proven as better option for effective and convenient drug delivery system also have emerged as a transformative drug delivery system, offering significant advantages for topical and transdermal applications. Their unique formulation, combining the properties of nanoemulsions and gels, ensures enhanced solubility, stability, and controlled drug release, making them ideal for treating a wide range of skin disorders, including seborrheic dermatitis, psoriasis, acne, and fungal infections.

The versatility of nanoemulgels extends beyond pharmaceutical applications, encompassing cosmetics, wound healing, and veterinary medicine, demonstrating their broad applicability and potential to meet diverse therapeutic needs. By overcoming challenges such as poor bioavailability and limited skin penetration of conventional formulations, nanoemulgels offer improved patient compliance and therapeutic outcomes. In conclusion, nanoemulgels represent a promising advancement in drug delivery systems, paving the way for innovative treatment strategies and further research into their development and clinical application.

REFERENCES

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  4. Abdussalam-Mohammed W. Review of Therapeutic Applications of Nanotechnology in Medicine Field and its Side Effects. J Chem Rev. 2019;1(3):243–51.
  5. P AK, Shabaraya AR. Nanoemulgel: a Review on Nanoemulgel. Certif J ? 552 Anju al World J Pharm Pharm Sci [Internet]. 2021;10(5):110. Available from: www.wjpps.com
  6. Dall’oglio F, Nasca MR, Gerbino C, Micali G. An Overview of the Diagnosis and Management of Seborrheic Dermatitis. Clin Cosmet Investig Dermatol. 2022;15(July):1537–48.
  7. Alhakamy NA, Md S, Alam MS, Shaik RA, Ahmad J, Ahmad A, et al. Development, optimization, and evaluation of luliconazole nanoemulgel for the treatment of fungal infection. J Chem. 2021;2021.
  8. Nagare J, Gondkar S. Formulation Development and Evaluation of Topical Nanoemulgel of Eberconazole Nitrate. 2022;9(8):50–71. Available from: www.jetir.org
  9. Tayah DY, Eid AM. Development of miconazole nitrate nanoparticles loaded in nanoemulgel to improve its antifungal activity. Saudi Pharm J [Internet]. 2023;31(4):526–34. Available from: https://doi.org/10.1016/j.jsps.2023.02.005
  10. Bhattacharya S, Prajapati BG. Formulation and optimization of celecoxib nanoemulgel. Asian J Pharm Clin Res. 2017;10(8):353–65.
  11. Priyadarshini P, Karwa P, Syed A, Asha AN. Formulation and Evaluation of Nanoemulgels for the Topical Drug Delivery of Posaconazole. J Drug Deliv Ther. 2023;13(1):33–43.
  12. Das S, Sharadha M, Venkatesh MP, Sahoo S, Tripathy J, Gowda D V. Formulation and evaluation of topical nanoemulgel of methotrexate for rheumatoid arthritis. Int J Appl Pharm. 2021;13(5):351–7.
  13. Anand K, Ray S, Rahman M, Shaharyar A, Bhowmik R, Bera R, et al. Nano-emulgel: Emerging as a Smarter Topical Lipidic Emulsion-based Nanocarrier for Skin Healthcare Applications. Recent Pat Antiinfect Drug Discov. 2019;14(1):16–35.

Reference

  1. Donthi MR, Munnangi SR, Krishna KV, Saha RN, Singhvi G, Dubey SK. Nanoemulgel: A Novel Nano Carrier as a Tool for Topical Drug Delivery. Pharmaceutics. 2023;15(1):1–28.
  2. Harshitha V, Swamy MV, Kumar DP, Rani KS, Trinath A. Nanoemulgel: A Process Promising in Drug Delivery System. Res J Pharm Dos Forms Technol. 2020;12(2):125.
  3. Prajapati B. ‘‘Nanoemulgel”Innovative Approach For Topical Gel Based Formulation. Res Rev Healthc Open Access J. 2018;1(2).
  4. Abdussalam-Mohammed W. Review of Therapeutic Applications of Nanotechnology in Medicine Field and its Side Effects. J Chem Rev. 2019;1(3):243–51.
  5. P AK, Shabaraya AR. Nanoemulgel: a Review on Nanoemulgel. Certif J ? 552 Anju al World J Pharm Pharm Sci [Internet]. 2021;10(5):110. Available from: www.wjpps.com
  6. Dall’oglio F, Nasca MR, Gerbino C, Micali G. An Overview of the Diagnosis and Management of Seborrheic Dermatitis. Clin Cosmet Investig Dermatol. 2022;15(July):1537–48.
  7. Alhakamy NA, Md S, Alam MS, Shaik RA, Ahmad J, Ahmad A, et al. Development, optimization, and evaluation of luliconazole nanoemulgel for the treatment of fungal infection. J Chem. 2021;2021.
  8. Nagare J, Gondkar S. Formulation Development and Evaluation of Topical Nanoemulgel of Eberconazole Nitrate. 2022;9(8):50–71. Available from: www.jetir.org
  9. Tayah DY, Eid AM. Development of miconazole nitrate nanoparticles loaded in nanoemulgel to improve its antifungal activity. Saudi Pharm J [Internet]. 2023;31(4):526–34. Available from: https://doi.org/10.1016/j.jsps.2023.02.005
  10. Bhattacharya S, Prajapati BG. Formulation and optimization of celecoxib nanoemulgel. Asian J Pharm Clin Res. 2017;10(8):353–65.
  11. Priyadarshini P, Karwa P, Syed A, Asha AN. Formulation and Evaluation of Nanoemulgels for the Topical Drug Delivery of Posaconazole. J Drug Deliv Ther. 2023;13(1):33–43.
  12. Das S, Sharadha M, Venkatesh MP, Sahoo S, Tripathy J, Gowda D V. Formulation and evaluation of topical nanoemulgel of methotrexate for rheumatoid arthritis. Int J Appl Pharm. 2021;13(5):351–7.
  13. Anand K, Ray S, Rahman M, Shaharyar A, Bhowmik R, Bera R, et al. Nano-emulgel: Emerging as a Smarter Topical Lipidic Emulsion-based Nanocarrier for Skin Healthcare Applications. Recent Pat Antiinfect Drug Discov. 2019;14(1):16–35.

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Rudranee Wagdare
Corresponding author

Dept. of Pharmaceutics, Channabasweshwar Pharmacy College (Degree), Latur.

Photo
Dr. Vijayendra Swamy S. M.
Co-author

Dept. of Pharmaceutics, Channabasweshwar Pharmacy College (Degree), Latur.

Photo
Atiya Shaikh
Co-author

Dept. of Pharmaceutics, Channabasweshwar Pharmacy College (Degree), Latur.

Photo
Amrapali Rajput
Co-author

Dept. of Pharmaceutics, Channabasweshwar Pharmacy College (Degree), Latur.

Photo
Maithili Kamble
Co-author

Dept. of Pharmaceutics, Channabasweshwar Pharmacy College (Degree), Latur.

Rudranee Wagdare*, Dr. Vijayendra Swamy S. M., Atiya Shaikh, Amrapali Rajput, Maithili Kamble, Nanoemulgel: A Novel Drug Delivery System for Enhanced Topical Treatments, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 6, 24-39. https://doi.org/10.5281/zenodo.15568521

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