Dept. of Pharmaceutics, Channabasweshwar Pharmacy College (Degree), Latur.
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.
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.
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)
Skin is composed of three main layers are as follows,
a. Epidermis
b. Dermis
c. Hypodermis
a. Epidermis:
c. Hypodermis/Subcutaneous layer:
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)
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.
2. Combination skin:
4. Sensitive skin :
Below are some key skin problems that can be effectively managed using nanoemulgels:v
1. Fungal Infections
2. Bacterial Infections
3. Acne Vulgaris
4. Psoriasis
5. Eczema and Dermatitis
6. Hyperpigmentation Disorders
Hyperpigmentation means that the skin looks darker than the normal skin(often brown to grey).
7. Burns and Wound Healing
8. Pain and Inflammation
9. Skin Cancer
10. Skin Aging (Cosmetic Applications)
11. Viral Skin Infections
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)
A. Physiological factors:
B. Physicochemical:
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)
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.
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).
Nanoemulgels are versatile, offering enhanced drug delivery, stability, and patient compliance across various fields.(13)
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
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