Formulation and Evaluation of Aspirin Emulgel using Natural Permeation Enhancers

Shaik Abdul Rehman¹, Shaik Jafar Ali¹, Chandra Sekhar Naik. D¹*, M. Janarthan²,

K. Uday Kiran¹, Md. Zulekha¹

¹Department of Pharmaceutics, Nimra College of Pharmacy, Ibrahimpatnam, NTR District, AP.

²Department of Pharmacology, Nimra College of Pharmacy, Ibrahimpatnam, NTR District, AP.

*Corresponding Author E-mail: chandu.desavath@gmail.com

ABSTRACT:

This research aimed to develop a stable aspirin emulgel and assess its effectiveness using natural penetration enhancers like olive oil, castor oil, and peppermint oil through a 2³-factorial design. The study focused on two key factors: viscosity and penetration rate. Eight formulations (F1 to F8) were created using HPMC and Carbopol 934 as gelling agents, chosen for their ability to manage the flow properties of topical gels. Among these, formulation F2 demonstrated ideal viscosity and penetration, further optimized with contour and 3D surface plots. The emulgel contained acetylsalicylic acid as the active drug, combined with Tween-20 (0.05%), PEG (0.6%), liquid paraffin (0.75%), Span-20 (0.1%), and 0.3% natural enhancers to ensure effective drug delivery. The results were promising, with the optimized formulation achieving 95.08% drug release within 6 hours and maintaining stability for up to 3 months. Microbial tests revealed that the optimized emulgel inhibited 46.6% of growth, significantly outperforming a marketed product that achieved only 32.3% inhibition. Safety was confirmed through skin irritation tests on rabbits, which showed no signs of redness, swelling, or irritation. Additionally, stability studies proved the emulgel retained its appearance, viscosity, drug release, and therapeutic activity over time. In conclusion, the aspirin emulgel formulation not only delivered the drug effectively in a sustained and controlled manner but also showed superior results compared to traditional cream formulations, making it a safer and more efficient alternative for topical drug delivery.

KEYWORDS: Emulgel, Aspirin.

INTRODUCTION:

Aspirin emulgels are a type of emulsion, both W/O and O/W, that are transformed into a gel by adding a gelling agent. This emulsified gel system is not only stable but also an effective carrier for medications that are hydrophobic or poorly soluble in water¹. Emulgels are widely accepted by patients because they combine the benefits of topical drug delivery with the analgesic and anti-inflammatory effects of gels and emulsions.

In O/W systems, lipophilic drugs (which dissolve in oil) are efficiently delivered, whereas hydrophilic drugs (water-soluble) are better suited for water-in-oil systems. Because of this versatility, emulgels have become an important option for delivering various hydrophobic drugs directly to the skin, ensuring better absorption and therapeutic outcomes.^1-2

There are two Emulgels available in the community market are jellified emulsion - Aspan gel containing aspirin as active pharmaceutical ingredient and deep relief gel containing aspirin combination with other analgesic like ibuprofen and menthol (Novartis Pharma, Switzerland), containing diclofenac diethyl amine (Medical Union Pharmaceuticals, Egypt).³

Topical drug administration serves as a localized delivery mechanism that allows drugs to be applied directly to specific areas of the body, including the skin, eyes, rectum, and vagina. Among these routes, the most accessible organ is the skin, for topical application and serves as the primary pathway for topical drug delivery. Emulgel formulations, which are hydrogels containing dispersed oil microdroplets, are particularly effective in this system.⁴ For ages, local skin conditions have been treated with topical medication delivery techniques. One benefit of topical administration is that it allows the medication to reach the afflicted area directly. while on the other, it allows the drug to act for an extended period, providing targeted treatment to the specific area. ⁵ Conversely, topical delivery methods increase local drug concentrations by extending the drug's residency and interaction times at the application site. Nevertheless, emulgel compositions pharmacological activity might not alter as rapidly as it does with solutions⁶. Various analgesic and anti-inflammatory agents are put up for sale in discrete topical forms, such as creams and ointments, designed to provide localized therapeutic effects⁶. Aspirin is one such anti-inflammatory agent, known for its both anti-inflammatory and analgesic effects. It is commonly applied locally to treat mild to moderate rheumatic pain and osteoarthritis discomfort⁷.

Because of their therapeutic advantages and ability to transport different medications to the skin, o/w and w/o emulsions are both frequently utilized. Emulsions can be readily removed when necessary and provide a certain elegance. Additionally, they penetrate the skin quite well. The viscosity, look, and greasiness of cosmetic or dermatological emulsions can also be altered by formulators. Whereas water-in-oil emulsions are more frequently employed to treat dry skin and provide emollient effects, oil-in-water emulsions are perfect for general cosmetic applications and as water-washable medication bases. Dermatological gels provide a number of benefits, including being emollient, non-staining, thixotropic, greaseless, easy to apply and remove, and compatible with a variety of excipients. They are also miscible or soluble in water. By changing the interactions between the oil droplets and the gel matrix, as well as the oil quantity and droplet size, gels with emulsified droplets can have different rheological characteristics and breakdown behaviours.

NECESSARIES AND PROCEDURE:

Necessaries:

Sample Aspirin was obtained from yarrow chemical, Mumbai, Carbopol 934, liquid paraffin, Tween 20, Span 20, propylene glycol, was procured from Lobe Chemicals, Mumbai. For every experiment, double-distilled water was used. Every substance was of pharmaceutical quality and was utilized exactly as it is.

Aspirin jellified emulsion composition:^8-9

A gellified emulsion was prepared by first dispersing Carbopol 934 in purified water with constant stirring at a moderate speed. Afterward, HPMC was added in the required quantity and the mixture was heated on a hot plate at 40-60°C for 30 minutes. The mixture was then cooled in a refrigerator at 2-4°C overnight. NaOH, or sodium hydroxide, was used to bring the pH down to 5.5 to 6.5. to achieve the desired viscous gel base, which serves as the matrix for drug delivery. For the emulsion, Span 20 was dissolved in liquid paraffin to create the oil phase, and Tween 20 was dissolved to create the watery phase. penetration enhancers (Peppermint, castor, and olive oils), and propylene glycol in purified water. Aspirin, the active ingredient, was also dissolved in the watery stage. Then, while stirring constantly, the oil phase was added to the aqueous phase. Finally, the required amount of the prepared gel base was mixed with the emulsion to form a satisfactory aspirin emulgel. This emulgel serves as an effective vehicle for drug delivery to the skin. The below table represents the quantities of the excipients and drug used in the formulation process.

The attributes of emulgel:^8-9

Aesthetic appearance:

Visual inspection was used to make sure the manufactured aspirin emulgel formulations fulfilled the required quality requirements for colour, Odor, homogeneity, and consistency.

Table No:1 formulation of Emulgel with Aspirin

Ingredient List	AF1	AF2	AF3	AF4	AF5	AF6	AF7	AF8
Drug	0.75%	0.75%	0.75%	0.75%	0.75%	0.75%	0.75%	0.75%
Carbopol	1%	1%	1%	1%	1%	1%	1%	1%
HPMC	0.5%	0.5%	0.5%	0.5%	0.5%	0.5%	0.5%	0.5%
PEG	0.5%	0.5%	0.5%	0.5%	0.5%	0.5%	0.5%	0.5%
Tween 20	0.05%	0.05%	0.05%	0.05%	0.05%	0.05%	0.05%	0.05%
Liquid paraffin	0.75%	0.75%	0.75%	0.75%	0.75%	0.75%	0.75%	0.75%
Olive oil	--	0.03%	--	0.03%	--	0.03%	--	0.03%
Castor oil	--	--	0.03%	0.03%	--	--	0.03%	0.03%
Peppermint oil	--	--	--	--	0.03%	0.03%	0.03%	0.03%
Span 20	0.1%	0.1%	0.1%	0.1%	0.1%	0.1%	0.1%	0.1%
H₂O	SQ	SQ	SQ	SQ	SQ	SQ	SQ	SQ

pH Test:

Take 10mg of the emulgel and disperse it in 10ml of distilled water. Measure the pH using a calibrated pH meter. The pH meter should be adjusted with standard buffer mixtures with pH values of 4.0, 7.0, and 10.

Spread ability:

Place 0.5mg of the emulgel between two glass slides (20 cm × 20cm). Apply a 500g weight on top of the slides for 5minutes. Afterward, measure the circumference of the spread emulgel using a scale or ruler.

Rheological Study:

Place the sample in the container and let it settle at 25°C for 30minutes using a Brookfield viscometer equipped with spindle 6. Make sure the spindle is positioned in the middle of the emulgel without touching the jar's bottom. After ten minutes of spinning the spindle at 12rpm, note the viscosity reading.

In vitro Release Study:

The Franz diffusion cell is employed as to study how drugs diffuse across a membrane. The receptor chamber is filled with an appropriate diffusion medium, like phosphate buffer, while being continuously stirred and kept at 37°C±0.5°C. The donor and the receptor are separated by an egg membrane. chambers, ensuring no air bubbles are trapped. The donor chamber is then loaded with the aspirin emulgel formulation. The system is sealed to prevent evaporation, and at specified intervals, samples are withdrawn from the receptor chamber through a sampling port and replaced with fresh medium. The collected samples are analysed using techniques like UV-Vis spectrophotometry to measure the drug's diffusion rate and profile.

Identifying the Drug Content:

A UV spectrophotometer was used to measure the amount of medication present in the aspirin emulgel. To find the aspirin concentration, a known amount of the emulgel was sonicated into methanol, and the absorbance at 275nm was measured following dilution.

Skin irritation test:

A 1" x 1" (2.54 x 2.54cm) piece of skin was covered with a double layer of gauze and a 0.5g sample of the test material was administered to each site (two sites per rabbit). The animals were put back in their cages after the emulgel was reapplied. The emulgel was taken off after a day, and any last traces were cleaned off the test locations using tap water.

Stability studies:

For three months, the manufactured aspirin emulgel formulations were kept at 25±2°C, 40±2°C, and 4±2°C in collapsible tubes that were kept out of direct sunlight. The materials were examined for physical characteristics, pH, and For safer use, consider rheological behavior, medication release, skin irritation, and microbiological activity.

OUTCOMES AND DISCUSSION:

Physical analysis reveals that the manufactured aspirin emulgel formulations (F2) are homogeneous, smooth, white, and viscous. The drug's physicochemical characteristics and melting point matched the specifications in the USP (2002), confirming the purity of the sample. Solubility tests showed that aspirin was slightly soluble in water but more soluble in chloroform, ethanol, acetone, and ether. The maximum absorption wavelength (λ max) for aspirin was found to be 275 nm. The below indicates the physical appearance of optimised formulation.

Table no. 2: Physical appearance of optimized formulation (F1 to F8)

S. no	Characteristics	Appearance
1	Colour	white
2	Odor	Mild, typically characteristic
3	Consistency	Semi-solid gel
4	Texture	Smooth and non-gritty
5	Homogeneity	Free from clumps, aggregates

Spread ability:

The spread ability values demonstrate that a little shear makes the emulgel easily spreadable. force. Formulation F2 demonstrated a spread ability of 2.4 cm/sec, which was better compared to the marketed gel. The spread ability of the formulations ranged from 2±2 minutes to 3.5±120 seconds, with F2 showing the highest spread ability at 2.4±40 seconds. The below figure and table represent the spread ability range of optimised formulation.

Table no. 3 Spread ability of optimised formulation

Formulation code	Diameter (cm)	Time
F1	2.5 cm	120 sec
F2	2.4 cm	40 sec
F3	2 cm	120 sec
F4	2.3 cm	13 sec
F5	2.9 cm	40 sec
F6	3 cm	15 sec
F7	2.5 cm	30 sec
F8	3.5 cm	95 sec

Figure no.1 Optimised formulation (F2)

Rheological investigations:

Viscosity measurements of the prepared emulgel were conducted using a Brookfield DV-E viscometer. Formulation F2 exhibited the highest viscosity, while F6 showed the lowest. The increased viscosity in F2 may be attributed to the lower concentration of emulsifying agents and liquid paraffin in the formulation. The below table and graph represents the rheological property range of the optimised formulation.

Table no.4 viscosity studies of optimized formulations

Formulation batch	Spindle No.	RPM	Viscosity (centipoise)
AF1	6	12	85000
AF2	6	12	93000
AF3	6	12	86000
AF4	6	12	89000
AF5	6	12	87000
AF6	6	12	80000
AF7	6	12	91000
AF8	6	12	90000

Graph no.1 Representation of rheological properties of optimised formulation.

pH test:

The pH values of every formulation that was created ranged from 5.4 to 6.4, which is suitable for avoiding skin irritation, as the normal pH of adult skin is around 5.5. The below figure and table indicate the Ph studies resulted from prepared optimised formulation.

Table no.5 pH studies of optimized formulation

Formulation table	pH
AF1	6.33±0.12
AF2	6.20±0.25
AF3	5.38±0.21
AF4	5.52±0.14
AF5	5.21±0.27
AF6	5.78±0.45
AF7	5.53±0.41
AF8	6.20±0.48

Figure no.2 pH of optimised formulation (F2)

Determination of drug amount:

The drug content in the aspirin emulgel formulations ranged from 88.78±1.82% to 95.75±1.20%, with formulation F2 showing the highest drug content at 95.75±1.20%. Additionally, F2 also exhibited the highest drug release among the formulations. The below table shows the % of drug content in optimised formulation.

Table no. 6 drug amount determination of optimized formulation.

Formulation code	Drug amount (%)
AF1	91%
AF2	95%
AF3	93%
AF4	92%
AF5	88%
AF6	89%
AF7	87%
AF8	90%

Skin irritation:

After applying the aspirin emulgel to the rabbit's skin for 24 hours, no signs of skin irritation were observed. The primary irritation test revealed that the emulgel formulation caused no irritation. The below figure represents the skin condition of rabbit before and after 24hr of emulgel application.

Figure no.3 Skin irritation result of the optimised formulation

Research on stability:

Following ICH criteria, stability experiments of the optimized formulation were carried out, and after three months, no discernible alterations were found. The emulgel remained stable in terms of pH, microbiological properties, In vitro drug release, skin irritation, and consistency. The composition showed no major alterations, confirming its stability throughout the 3-month period under all storage conditions. The below table reflects about the stability aspects of prepared optimised formulation over period of 3 months.

Table no. 7 Stability studies of optimised formulation (F1 to F8)

S. No	Properties	Observation
1	Colour (first)	Colourless
2	Colour (One month later)	Colourless
3	pH (First)	6.2
4	pH (one month later)	6.2
5	proportion of drug content	94%

Release of drugs:

The aspirin in vitro release patterns of several emulgel formulations showed a good drug release across all formulations. The drug release after 6 hours ranged from 87.12% to 95.98%, with the formulations ranked in descending order of release. Notably, the prepared F2 formulation of aspirin emulgel demonstrated a better release profile compared to the marketed preparation.

Evaluation of Aspirin Emulgel Through 2³ Factorial Design:

a) Counter plot

b) Response surface plot

Figure no. 3 (a) Counter plot (b) Response surface plot of Aspirin emulgel

Source	Sum of Squares	df	Mean Square	p-value
Model	1.159E+08	7	1.655E+07	P<0.5
A-Olive oil	1.513E+07	1	1.513E+07	P<0.5
B-Castor oil	7.812E+07	1	7.812E+07	P<0.5
C-Peppermint oil	3.125E+06	1	3.125E+06	P<0.5
AB	1.250E+05	1	1.250E+05	P<0.5
AC	3.125E+06	1	3.125E+06	P<0.5
BC	1.125E+06	1	1.125E+06	P<0.5
ABC	1.512E+07	1	1.512E+07	P<0.5
Pure Error	0.0000	0		P<0.5
Cor Total	1.159E+08	7

ANOVA for factorial model of viscosity:

a) Counter plot

b) Response surface plot

Figure no. 4 (a) Counter plot (b) Response surface plot of Aspirin emulgel

Source	Sum of Squares	df	Mean Square	p-value
Model	4530.00	7	647.14	P<0.5
A-Olive oil	1012.50	1	1012.50	P<0.5
B-Castor oil	364.50	1	364.50	P<0.5
C-Peppermint oil	722.00	1	722.00	P<0.5
AB	450.00	1	450.00	P<0.5
AC	420.50	1	420.50	P<0.5
BC	760.50	1	760.50	P<0.5
ABC	800.00	1	800.00	P<0.5
Pure Error	0.0000	0
Cor Total	4530.00	7

ANOVA for factorial model of percentage of drug release:

A polynomial regression approach was employed to investigate the connection between the independent and response variables. This method uses a second-order model, which was expressed as an equation based on the 2n experimental design. Y is equal to β0 + β1A + β2B + β3C + β1β2 AB + β1 β3 AC + β2β3 BC + β1β2 β3 ABC.

Where, Y is the measured response.

β0 is the arithmetic mean response.

Factors A, B, C, AB, AC, BC, and ABC have the following coefficients: β1, β2, β3, β1β2, β1β3, β2β3, and β1β2β3 respectively. These represent the percentages of Olive oil, Castor oil, Peppermint oil, and their interactions. The coefficients were determined using the following equation.

 β = Σ XY/2n.

Where, β: Coefficient.

 X: Penetration enhancers (A, B, C).

 Y: Response value (Percentage of drug release and viscosity range).

 n: Level.

The mathematical model for Penetration Time (PT) was found to be quite complex. However, the effects of the main factors and their interactions on PT were clarified using contour and 3D response graphs. The contour plot revealed a linear relationship, suggesting that the permeation enhancers, such as Olive oil in relation with the Castor oil, and Peppermint oil which may held constant, may lead to faster penetration. The 3D response and surface plots further illustrated this, showing that the concentration of permeation enhancers 0.3% influences the emulgel's penetration time.

Final equation in terms of coded factors:

Effect of viscosity in suitable time period = +87625.00-1375.00A+3125.00B

-625.00C+125.00AB-625.00AC+375.00BC+1375.00ABC.

Effect of percentage of drug release in suitable time period = +85.00+11.25A+6.75B+9.50C

-7.50AB-7.25AC-9.75BC+10.00ABC.

When examining the effect of Castor oil (B) and Olive oil (A) on viscosity and the percentage of drug release over a suitable time period, it becomes clear that higher concentrations of Olive oil increase the penetration percentage. The presence of other penetration enhancers, such as Peppermint oil (C) and Castor oil (B), also positively influence the viscosity range and the drug release percentage. Figure 3a shows a linear relationship between the concentrations of Olive oil (A) and Castor oil (B) and the percentage of drug released within this range. Specifically, when Olive oil (A) and Castor oil (B) are between 0.06% and 0.03%, the viscosity range and drug release fall between 0% to 0.18%. Additionally, a non-linear behaviour is observed in both viscosity and drug release between 0.024% and 0.03%. As a result, a higher percentage of the Aspirin emulgel penetrates fully within the suitable time period.

Optimum Formula:

When examining the effect of Castor oil (B) and Olive oil (A) on viscosity and the percentage of drug release over a suitable time period, it becomes clear that higher concentrations of Olive oil increase the penetration percentage. The presence of other penetration enhancers, such as Peppermint oil (C) and Castor oil (B), also positively influence the viscosity range and the drug release percentage. Figure 3a shows a linear relationship between the concentrations of Olive oil (A) and Castor oil (B) and the percentage of drug released within this range. Specifically, when Olive oil (A) and Castor oil (B) are between 0.06% and 0.03%, the viscosity range and drug release fall between 0% to 0.18%.

Additionally, a non-linear behaviour is observed in both viscosity and drug release between 0.024% and 0.03%. As a result, a higher percentage of the Aspirin emulgel penetrates fully within the suitable time period. Formulation F2, which used a 0.3% concentration of Olive oil, demonstrated a higher percentage of drug release within the desired time frame and a satisfactory viscosity range. This formulation is considered the best for Aspirin emulgel, offering results comparable to Formulation F8, which contains three penetration enhancers, including a novel natural one. However, F2 was found to be more economical, as it uses a single, novel penetration enhancer.

CONCLUSION:

It was found that the formulation containing olive oil was a clear, emollient oil that facilitated quick penetration. To develop aspirin emulgel using a 2³ factorial design, olive oil was selected as the sole penetration enhancer. The optimized aspirin emulgel formulation (F2), with 0.3% olive oil, demonstrated an ideal viscosity range, maximum drug release, and better viscosity compared to other formulations, including commercially available ones. This modified formula showed enhanced drug absorption, improved bioavailability, and rapid achievement of peak plasma concentrations. The study results confirmed that olive oil enhanced penetration effectively, making it a promising penetration enhancer for emulgels containing poorly soluble drugs.

REFERENCES:

1. Siti Norfarhani. Sakina Ruhi. Ram k Sahu et al. Development and evaluation of topical emulgel of aspirin using different polymeric bases. Research Journal of Pharmacy and Technology. 2020; 13(12): 6300-6304. DOI: https://doi.org/10.5958/0974-360x.2020.01096.3

2. Parihar N. Saini M. Soni SL. Sharma V. Emulgel: A Topical Preparation, Asian Journal of Pharmaceutical Research and Development. 2020; 8(3): 196-201. DOI: http://dx.doi.org/10.22270/ajprd.v8i.765

3. Ashima Chandel. Neha Kumari et al An Overview on Emulgel. Asian Journal of Pharmaceutical Research. 2023; 13(3): 196-9. DOI: https://doi.org/10.52711/2231-5691.2023.00037

4. Rutuja Saurabh Shah. Formulation and evaluation of turmeric emulgel. Asian Journal of Pharmaceutical Research and Development. 2021; 11(3): 213-9. DOI: https://doi.org/10.52711/2231-5713.2021.00035

5. Junaid S Shaikh. Shashikant et al Formulation and Evaluation of Ketoprofen Emulgel for topical drug delivery system. 2024; 14(1): 9-2. DOI: https://doi.org/10.52711/2231-5713.2024.00003

6. Rohini Reddy. Shanthi Priya et al Formulation and Evaluation of Naproxen emulgel for topical drug delivery. Research Journal of Pharmacy and Technology. 2021; 14(4): 1961-5. DOI: https://doi.org/10.52711/0974-360x.2021.00347

7. Monica Rao. Sheetal Aghav et al Optimization of Metronidazole Emulgel. Journal of Pharmaceutics. 2013; 1(1): DOI: https://doi.org/10.52711/0974-360x.2021.00347

8. Ghada Yassin. Formulation and Evaluation of Optimized Clotrimazole Emulgel Formulation. British Journal of Pharmaceutical Research. 2014; 4(9): 1014-1030. DOI: https://doi.org/10.9734/bjpr/2014/8495

9. Magdy I. Mohamed. Optimization of Chlorphenesin emulgel Formulation. American Association of Pharmaceutical Scientists. 2004; 6(3): DOI: https://doi.org/10.1208/aapsj060326

Received on 26.12.2024      Revised on 19.04.2025

Accepted on 17.07.2025   Published on 10.02.2026

Available online from February 16, 2026

Research J. Pharmacy and Technology. 2026;19(2):873-878.

DOI: 10.52711/0974-360X.2026.00124

© RJPT All right reserved

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.