Development and Evaluation of topical Emulgel of Aspirin using different Polymeric Bases


Jiyauddin Khan1*, Siti Norfarhani1, Ram K Sahu3, Sakina Ruhi2, Mohammed Kaleemullah1, Samer Al-Dhalli1, Mohamed Rasny1, Sri Budiasih1, Shariq Baber1, Chean Hui Ng1, Nik Nur Shamiha1, Gulam Muhammad Khan4, Gamal O. E.5, Santosh Fattepur1, Kiran Nilugal1, Ibrahim Abdullah1, Fadli Asmani1, Eddy Yusuf1

1School of Pharmacy, Management and Science University, 40100 Shah Alam, Selangor, Malaysia.

2International Medical School, Management and Science University, 40100 Shah Alam, Selangor, Malaysia.

3Department of Pharmaceutical Sciences, Assam University, Silchar, Assam 788011, India.

4School of Health and Allied Sciences, Pokhara University, Kaski, Nepal.

5Department of Pharmaceutics, Unaizah College of Pharmacy, Qassim University, KSA.

*Corresponding Author E-mail:



The purpose of the study was to prepare a stable Aspirin Emulgel. Carbopol 940 and Hydroxypropyl methyl cellulose (HPMC) were used as gelling agent which has good viscosity which makes them fairly popular for controlling the flow properties of topically applied dosage forms as they are inexpensive, transparent, harmless, east to wash and prepare. Oral Aspirin generate a gastrointestinal side effects such as ulceration, and perforation when Aspirin drug was taken orally. In this research, Acetylsalicylate acid was active ingredient, Carbopol and HPMC were gelling agent and distilled water as solvent. Emulsion contains Tween 80 and Span 80 was mixed into gel base. The finished formulation gives whitish colour for formulation using Carbopol, while transparent colour for formulation using HPMC. Stability studies were performed at different storage conditions; 2-4 oC (Cool room), 25 oC (Room temperature) and 40 oC (Oven) for 28 days to predict the stability of formulations. For formulation using Carbopol, there were no changes in color, stickiness, homogeneity, phase separation and centrifugation in formulation stored at 2-4 oC, 25 oC and 40 oC for 28 days. While for formulation using HPMC, there is no no changes in colour, stickiness, homogeneity, phase separation and centrifugation in formulation at 2-4 oC, and 25 oC but present of stickiness in formulation when kept at 40 oC for 28 days. Based on one-way ANOVA test at the 5% significance level that changes in pH values of sample was not significant at different level of time and temperature (p>0.05).


KEYWORDS: Aspirin, Carbopol 940, HPMC, Tween 80, Span 80, Emulgel.




Aspirin is a non-steroidal anti-inflammation drug (NSAID). It widely uses as analgesic, anti-inflammatory, antipyretic and an inhibitor of platelet aggregation [1]. Aspirin is an ester of salicylic acid, while after ingestion it will undergoes hydrolysis which produces salicylic acid and acetic acid. Acetyl salicylic acid is a weak acid (pKa = 3.5) that can be absorbed across the mucosal lining of the stomach. Salicylates is the inhibition of the formation of prostaglandins and can induce irritation in lining of stomach which can cause bleeding even in normal dosage. Other side effects are nausea, vomiting and dizziness when taking orally [2].

The advantage of emulgel for dermatological use have several favourable properties such as being thixotropic, greaseless, easily spreadable, easily removable, emollient, non-staining, water-soluble, longer shelf life, bio-friendly, transparent and pleasing appearance [3].


The emulgel formulation is chosen because several studies show that Aspirin as hydrophobic compound that insoluble in water but soluble in oil. Gel formulations commonly provide faster drug release compared with conventional ointments and creams. In spite of many advantages of gels, there has one major limitation is the difficulty in delivery of hydrophobic drugs. Therefore, to overcome this limitation, emulgel are prepared to make hydrophobic drug can enjoy the unique properties of gels. When gels and emulsions are used in combined form the dosage forms are referred as Emulgel.


Aspirin is a derivative of salicylic acid, making it a member of the salicylate family of compounds. Salicylates are natural compounds found in plants such as the willow tree, that are widely used therapeutics commonly used to relieve pain, fever, and inflammation. Aspirin is chemically designated as acetylsalicylic acid and has a chemical structure that is consist of three chemical groups, an ester group, an aromatic ring, and a carboxylic acid group. The disadvantages of aspirin include ulceration and stomach bleeding, allergic reactions and Reye's syndrome in children (a potentially fatal liver and brain disorder). Overdosage can lead to serious liver damage, brain damage and death [4].


Anti-inflammatory mechanism of Aspirin by decrease prostaglandin synthesis via inhibition of COX-1 and COX-2. The anti-inflammatory effects may be primarily due to inhibition of the COX-2 isoenzyme. But, COX-1 also has effect at some sites of inflammation [5].


Aspirin is effective to treat inflammation caused sensitivity of pain receptors. Specifically, prostaglandin E and F are responsible for sensitizing the pain receptors, so NSAIDs have an indirect analgesic effect by inhibiting the production of further prostaglandin and does not directly affect pain threshold. Higher doses are required for analgesic versus anti-inflammatory [5].


The absorption rate of acetylsalicylic acid is rapidly and completely absorbed, Tmax is 1 to 2 h. It is widely distributed to all tissues and fluids, central nervous system, breast milk, and fetal tissues. Approximately 90% of salicylate is protein bound at concentrations of less than 100 mcg/mL and approximately 75% is bound at concentrations of more than 400 mcg/mL. For metabolism, aspirin rapidly hydrolyzed to salicylic acid (active). Salicylic acid is conjugated in the liver to the metabolites. Salicylic acid plasma half-life is approximately 6 h, but may exceed 20 h in higher doses. The half-life is approximately 15 to 20 min for aspirin. Elimination follows zero-order kinetics. Renal elimination of unchanged drug depends on urine pH. A pH of more than 6.5 increases renal clearance of free salicylate from less than 5% to more than 80% [5].


Emulgel are emulsions, either of the oil-in-water or water in oil type, which are mixing with a gelling agent such as Carbopol or Hydroxypropyl methylcellulose. Emulgel is stable and better vehicle for hydrophobic or poorly water soluble drugs such as aspirin or ibuprofen. Direct (Oil-in-water) systems are used to entrap lipophilic drugs, whereas hydrophilic drugs are encapsulated in the reverse (water-in-oil) systems. Therefore, they have been recently used as vehicles to deliver various hydrophobic drugs to the skin. Both oil-in-water and water-in-oil emulsions are extensively used for their therapeutic properties and as vehicles to deliver various drugs to the skin. Emulsions are easily washed off whenever desired and also have a high ability to penetrate the skin. Oil-in-water emulsions are most useful as water washable drug bases and for general cosmetic purposes, while water-in-oil emulsions are usually use in treatment of dry skin and emollient applications. Gels have several favorable properties such as being thixotropic, greaseless, easily spreadable, easily removable, emollient, non-staining, compatible with several excipients, and water-soluble. Thus, by mixing gels with emulsions droplets can changing the interactions between oil droplets and gel matrix, the oil content and the oil droplet size [6]. Hence, it was planned to formulate stable Aspirin Emulgel by using polymer namely carbopol 940 and Hydroxypropyl methyl cellulose (HPMC).




Aspirin, distilled water, Carbopol 940, hydroxypropyl methylcellulose (HPMC), tween 80, span 80, liquid paraffin, triethanolamine, methyl paraben, propylene glycol, mentha oil. (All chemicals were obtained from Management and Science University, Pharmacy Laboratory).



Measuring cylinder, beaker, mortar and pestle, spatula, glass rod, dropper, pipette, weighing boat, magnetic stirrer, aluminium foil, centrifuge tube, urine container, conical flask, syringe, needle, weighing balance, digital pH meter, centrifuge, oven, brook-field viscometer, and homogenizer. (All apparatus or equipments were obtained from Management and Science University, Pharmacy Laboratory)


Preparation of Gel Base:

Gel base were prepared by dispersing different concentration of carbapol 940 into distilled water separately with constant stirring using magnetic stirrer until the transparent gel was formed. While different concentration of HPMC were prepared by disperse in heating distilled water (80 oC), then dispersion were allowed to cool at cold room (2-4 oC) for overnight. pH of all formulations are adjusted to 4.5 to 6 by using triethanolamine.


Preparation of Emulsion:

The aqueous phase was prepared by dissolve Tween 80 in distilled water. While, the oil phase was prepared by dissolve lipophilic surfactant, Span 80 in paraffin oil separately. Metha oil was added into oil phase as penetration enhancer. Methyl paraben was mixed together, whereas aspirin powder was dissolved in propylene glycol and added methyl paraben to the mixture and the mixture was mixed with aqueous phase. Then, two phases of emulsion were heated separately at 70 -80 °C until the powder mixtures were homogeneous. Next, added oil phase into aqueous phase with continuous stirring using homogenizer for two hours and cool at room temperature (Table 1).


Table 1: Composition of different drug formulation 1% of Aspirin Emulgel

Ingredient (% w/w)

Drug Formulation Code (%)










Carbopol 940





Carbopol 934










Tween 20





Span 20





Liquid Paraffin





Metha oil





Methyl paraben





Propylene glycol






q. s

q. s

q. s

q. s


Evaluation of Prepared Emulgel:

Physical Examination:

The prepared emulgel were inspect visually by their color, stickiness, grittiness and homogeneity. The prepared emulgel were subjected to stability studies at different temperatures (4, 25 and 40 oC) and evaluated periodically every week for 28 days [6].


Phase Separation:

5 g of emulgel from each formulation were centrifuged for 15 minutes at 3000 rpm. This centrifugation test was conduct on each formulation emulgel room temperature (4, 25 and 40 oC) at 1st, 7th, 21st, and 28th. Phase separation was observed visually for appearance [7].


pH study:

2 grams of prepared emulgel were dissolved in 100 ml of phosphate buffer and was measure by using digital pH meter. pH of emulgel were adjusted in range 5.4 to 5.8 by using triethanolamine as pH of human skin typically range from 4.5 to 6.0 during the formulation. The measurement were performed at 1st, 7th, 14th,21st, and 28th day three different temperature 4oC, 25oC and 40oC to detect any pH fluctuation with time [8,9].


Rheological Study:

The viscosity of each formulation were determined using Brookfield Viscometer with spindle 08. The sample added to the sample container and allows to settle down for 30 minutes at temperature 25 oC. The spindle placed in centre of emulgel and make sure that spindle does not touch bottom of jar and will be rotated at speed 50 rpm for 10 minutes. Then, viscosity reading is recorded. Next, the emulgel was rotated at different speed of 20 rpm, 40 rpm and 60 rpm respectively for 10 minutes.


In-Vivo Anti-inflammatory activity study:

Six groups of mice will be injected of 0.1 ml of 1% (w/v) carrageenan on left hind paw of the rats. Standard and treated group were applied topically apply with aspirin emulgel before 30 minutes injection of carrageenan. Standard group was applied with marketed diclofenac diethyl-ammonium emulgel. Diameter of paw for each mice were measured before and after injected with formalin. Each mice was injected with 0.05 ml of 2 % of formalin on left hind paw of the mice and time interval 2, 4 and 6 hours later, the paw diameter were measured. The paw diameter was measured and the percent inhibition of edema is calculate using following formula.


Equation 1: Formula of percentage of edema inhibition:


               Mean paw diameter (Control) – Mean paw diameter (Treated)

Inhibition (%) =---------------------------------------------------------- X 100

                             Mean paw diameter (Control)  



Stability tests were performed at three different storage conditions. The samples were kept at cool room (2-4 oC), room temperature (25 oC) and oven (40 oC) for 0 h, 24 h, 7 days, 14 days, 21 days and 28 days. Formulation 1 and formulation 2 were white milky appearance with smooth, no grittiness, no stickiness, good consistency and homogeneous as well as no phase separation (Fig 1 and Fig 2). Formulation 3 and formulation 4 were transparent appearance with smooth, no grittiness, no stickiness, homogeneous and no phase separation (Fig 3 and Fig 4). However, formulation 3 and formulation 4 were present of stickiness when kept at oven (40 oC) which shown poor stability (Fig. 5).



Fig 5: Shows result for phase separation for formulation 1, formulation 2, formulation 3, and formulation 4


The pH value of aspirin emulgel were in range between 4.5 to 6.0. This is consider acceptable pH to avoid irritation of human skin (Fig. 6). The pH value should not fluctuate and still after 28 days for all formulations. The mean of the sample stored at cool room (2-4 oC) was 5.65. Meanwhile, mean pH of sample stored at room temperature (25 oC) was 5.48. Furthermore, mean pH of sample stored at oven (40 oC) was 5.42.


For rheological study, viscosity of the emulgel will be increase as increase of concentration of polymer (Fig. 7). The use of 1.5% carbapol polymer has higher viscosity. It offers an effective and successful gel base for the topical delivery of aspirin as an emulgel because it has highest viscosity structure which is still in acceptable range and best drug diffusion. While 2% of HPMC is has lowest viscosity which not suitable for drug diffusion and human compliance.


Fig. 6: pH value of Emulgel Aspirin at different storage conditions



Fig. 7: Rheological study using HPMC


In the experiment, there were no significant differences in the extent of the edema between the prepared gel formulation group, the formalin-induced edema group and the aspirin 1%, at any time of the experiment. Group F5 (1% aspirin and 2% HPMC) has the lowest mean percentage edema inhibition, which the result was 14.9 %. For groups 4 (1% aspirin and 1.5% Carbopol 940) at reading time of 6 hours, had significantly larger edema inhibition with 31.6% at 6 hour and higher mean percentage of edema inhibition was 18.5% compared to another treated group. For standard group (Diclofenac diethyl ammonium), the mean percentage of inhibition of edema was 20.2% (Fig. 8).



Fig 8: Comparison of rats percentage of edema inhibition of control, treat and standard



Aspirin emulgel was prepared and successfully formulated into topical application using Carbopol 940 and hydroxypropyl methyl cellulose as gelling agent. This formulation approach can be used to improve limitation of oral Aspirin. Formulation 2 which consist 1% of aspirin and 1.5% Carbopol 934 shows the best stability profile, higher viscosity and larger percentage of edema inhibition. The formulation had demonstrated that were stable colour, homogeneity, pH, texture and phase separation for period up to 28 days at three different storage conditions. The objective of the research on developing a stable Aspirin emulgel formulation has been achieved.



Recommended for further stability test should be conducted. For example, stability test, pH study, rheological study, centrifugation study and In-vivo anti-inflammatory can be conducted for a several months. In addition, recommended for availability of Plethynomometer equipment for further analysis of anti-inflammation study.



Develop innovative technologies in areas such as drug delivery and therapeutic cells/tissues, clinical biomarkers, biochips for real-time and remote monitoring or drug delivery



The authors are gratefully acknowledged to the School of Pharmacy, Management and Science University, Shah Alam, Selangor Darul Ehsan, Malaysia for providing the necessary facilities to carry out the research project successfully.



Authors declared no conflict of interests.



1.      Greenstein B, Greenstein A. Concise Clinical Pharmacology. Pharmaceutical Press. UK. 2007; 84-85.

2.      Vane JR, Botting RM. Thrombosis Research. Indian J Pharm Science. 2003; 1:255-258.

3.      Mohammed Haneefa KP. The Advantage of Emulgel. J. Pharm. Sci. and Res. 2013; 5(12): 254 - 258.

4.      Wiley J, Sons I. History of Aspirin and Mechanism of Action of Aspirin. 2013; 519.

5.      Williams DA, William OF, Thomas LL. Foye's Principles of Medicinal Chemistry. 5th edition. Baltimore: Lippincott Williams and Wilkins. 2002; 364.

6.      Jain A, Gautan SP, Gupta Y. Development and characterization of ketoconazole emulgel for topical drug delivery. Der Pharmacia Sinica, 2010; 1(3): 221-231.

7.      Kalpesh CA, Jalpa SP. Microemulgel an ovelhelming approach to improve therapeutic action of drug moiety. Saudi Pharmaceutical Journal. 2014; 1(4):5-10.

8.      Kaur LP, Garg R., Gupta GD. Development and evaluation of topical gel of minoxidil from different Polymer bases in application of alopecia. International Journal Pharmacy and Pharmacy Science. 2010; 2(3): 43-47.

9.      Cecv G. Preclinical characterisation of NSAIDs in ultra deformable carriers or conventional topical gels. International Journal of Pharmaceutics. 2008; 360(1-2): 29-39.






Received on 11.07.2019           Modified on 09.12.2019

Accepted on 17.03.2020         © RJPT All right reserved

Research J. Pharm. and Tech. 2020; 13(12):6300-6304.

DOI: 10.5958/0974-360X.2020.01096.3