Formulation and Evaluation of Quercetin Nanoemulsion Gel for Rheumatoid Arthritis

Mamaniyat Samiha Mahmad*, Mahek Gani Deshmukh, Khan Muklisa Aslam, Afira Aabeda Mohammad Naseem

JIIU’s Ali Allana College of Pharmacy, Akkalkuwa, Dist: Nandurbar, Maharashtra, India

*Correspondence: mamaniyatsamiha786@gmail.com;

DOI: https://doi.org/10.71431/IJRPAS.2026.5612  

INTRODUCTION

Rheumatoid Arthritis (RA) is a chronic, systemic autoimmune disease that causes progressive cartilage degradation, bone erosion, pain, and functional impairment. Persistent inflammation of synovial joints is the hallmark of rheumatoid arthritis (RA)[4,5].About 0.5–1% of people worldwide are affected, and it considerably lowers quality of life while raising the cost of healthcare[3,4]. Tumour necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6) are among the pro-inflammatory cytokines that are released as a result of the disease's complex immunological mechanisms, which involve the activation of T cells, B cells, and macrophages. These cytokines are crucial in the degradation of joints[5].

Current pharmacological treatments for RA, such as corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), and disease-modifying antirheumatic drugs (DMARDs), are linked to a number of drawbacks, including organ toxicity, immunosuppression, gastrointestinal irritation, and negative long-term effects. Additionally, systemic administration frequently results in decreased patient compliance and non-specific drug distribution. These drawbacks emphasise the need for safer and more potent alternative treatment approaches[4].

Quercetin due to its strong anti-inflammatory, antioxidant, and immunomodulatory qualities, a naturally occurring flavonoid found in many fruits and vegetables, has been the subject of much research[6,7]. It scavenges free radicals, inhibits lipid peroxidation, suppresses the production of inflammatory cytokines, and modifies signalling pathways like nuclear factor-kappa B (NF-κB) to achieve its pharmacological effects[6,7]. Because    of these characteristics, quercetin is a potentially effective treatment for inflammatory conditions like rheumatoid arthritis[8].

However, quercetin's poor aqueous solubility, low bioavailability, quick metabolism, and restricted permeability across biological membranes severely restrict its clinical use. To improve its therapeutic efficacy, these difficulties call for the creation of sophisticated drug delivery systems[10,11]. Nanoemulsion-based drug delivery systems have become one of the most successful methods for increasing the solubility, stability, and bioavailability of medications that are poorly soluble in water. With droplet sizes usually in the nanometre range, nanoemulsions—isotropic, thermodynamically stable systems made of oil, water, surfactant, and co-surfactant—offer increased surface area and better drug absorption[12,13].

Additionally, topical drug delivery systems minimise systemic side effects and improve therapeutic outcomes by delivering the medication directly to the site of inflammation, which is a major advantage in the management of rheumatoid arthritis. Viscosity, spreadability, and patient acceptability are improved when nanoemulsion is incorporated into a gel base (nanoemulgel), making it appropriate for dermal application. This combination offers controlled and prolonged drug release in addition to enhancing drug penetration through the skin[15,20].

In order to effectively treat rheumatoid arthritis topically, the current study focuses on the development and assessment of a quercetin-loaded nanoemulsion gel. The developed formulation seeks to increase quercetin's bioavailability and therapeutic efficacy while overcoming the drawbacks of traditional therapy. The formulation's suitability for topical application was assessed using a number of physicochemical parameters, such as pH, spreadability, drug content, and stability[1,2,23].

METHODOLOGY

1          Pseudo-ternary Phase Diagram Construction :-

·         To identify the nanoemulsion region and optimize the oil, surfactant, and co-surfactant ratio, a pseudo-ternary phase diagram was created.

·         Solubility studies were used to choose the appropriate oil, surfactant, and co-surfactant (without adding the medication).

·         To create Smix, surfactant and co-surfactant were combined in various proportions :-

a.       1:1

b.      2:1

c.       3:1

d.      4:1 

·         Various volume ratios of oil and Smix were combined :-

1)      1:9

2)      2:8

3)      3:7

4)      4:6

5)      5:5

6)      6:4

7)      7:3

8)      8:2

9)      9:1

·         With constant stirring, each mixture was gradually titrated with deionized water.

·         The clarity and turbidity of the mixtures were visually assessed.

·         To determine the nanoemulsion region, the findings were displayed on a pseudo-ternary phase diagram.

·         The final oil-in-water (O/W) nanoemulsion with HLB range 8–18 was prepared using the Smix ratio that generated the biggest clear monophasic nanoemulsion area[12,13].

2          Preparation of Nanoemulsion :-

·         In the oil phase, quercetin was dissolved.

·         Smix was created by combining surfactant with co-surfactant.

·         Smix was given an oil phase.

·         Stirring, distilled water was gradually added.

·         To create the nanoemulsion, high-speed homogenization was used(10,12).

3          Preparation of Nanoemulsion gel :-

·         After being dissolved in distilled water, carbopol 934 was left to swell.

·         The gel basis was mixed with nanoemulsion.

·         To change the pH and create gel, triethanolamine was used.

·         As a preservative, methyl paraben was added.

·         To create a homogenous nanoemulsion gel, the mixture was agitated[15,20].

Evaluation Parameters :-

1.      Phytochemical tests^[21,22] :-

2.      Evaluation of Quercetin Nanoemulsion Gel :-

       I.            Physical Appearance :-

a.       Colour :- Light yellow or pale yellow

b.      Homogeneity :- Lump-free, uniform

c.       Consistency :- semi-solid and smooth

d.      Clarity :- Uniform and slightly translucent

e.       Particles :- No particles are visible^[1,2,15].

    II.            pH :-

·         Method :-

§  One gram of gel should be weighed and then dissolved in ten milliliters of distilled water.

§  Give it two hours to stand.

§  Use a digital pH meter that has been calibrated to measure pH.

·         Acceptable Range :- 5.5 to 7.0^[23]

 III.             Spreadability :-

·         Method :-

§  One gram of gel should be sandwiched between two glass slides.

§  Use the 500 g standard weight.

§  Calculate how long it takes to separate.

§  Use the following  formula to determine spreadability.

S = (M × L) / T

where ,

S stands for spreadability.

M is the weight attached to the top slide.

L stands for slide length.

T stands for time spent.

·         Acceptable Range :- 5–8 g·cm/sec^[15]

               IV.            Drug Content Uniformity :-

·         Method :-

§  Weigh one gram of gel, then dissolve it in methanol.

§  After 15 minutes of sonication, filter.

§  Use a UV spectrophotometer set to 370 nm for analysis.

·         Acceptable Range :- 90–110%^[1,2]

RESULT

In order to create an optimum formulation with desired physicochemical and performance properties, three quercetin nanoemulsion gel formulations (F1, F2, and F3) were successfully developed.
A number of evaluation criteria, such as appearance, pH, viscosity, spreadability, drug content were applied to all three formulations. The results showed discernible changes across the formulations, mostly as a result of variances in excipient content and composition.
Formulation F1 had better qualities than Formulations F2 and F3. The nanoemulsion system's stability was demonstrated by its homogeneous, smooth appearance and lack of phase separation. F1's pH was found to be within the permissible range for skin compatibility, indicating that it could be used topically without causing irritation.

Formulation F1 was deemed the optimal batch based on the overall evaluation results because of its superior stability, physicochemical features. Therefore, F1 can be considered a promising formulation for quercetin topical administration.

CONCLUSION

The study showed that a gel based on quercetin nanoemulsion is a promising topical formulation for the treatment of rheumatoid arthritis. Quercetin's solubility, stability, and skin penetration are all greatly improved by the nanoemulsion system.

The formulation had an acceptable pH, good spreadability, high drug content, and improved skin penetration, according to evaluation results. Additionally, the nanoemulsion gel demonstrated strong physical stability.

With fewer systemic side effects and better patient compliance, quercetin nanoemulgel can be regarded as a successful alternative treatment for rheumatoid arthritis.

ACKNOWLEDGMENT

We would like to express my special gratitude to Dr. G. J. Khan, Principal, JIIU'S Ali Allana College of Pharmacy Akkalkuwa and Management of Jamia Islamia Ishaatul Uloom Akkalkuwa for their continuous motivation and providing all necessary facilities during completion of this work.

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