1. INTRODUCTION:

Mouth ulcers, or aphthous stomatitis, are painful lesions of the oral mucosa that affect areas such as the lips, tongue, cheeks, and palate. Though often self-limiting, these ulcers can significantly impair daily activities like eating, speaking, and maintaining oral hygiene. Common causes include mechanical trauma, stress, nutritional deficiencies, food sensitivities, hormonal changes, and underlying systemic conditions ^1,2,3

Conventional treatments rely on corticosteroids, antiseptics, and topical anaesthetics, which help alleviate symptoms but may lead to adverse effects with prolonged use, such as mucosal thinning, allergic reactions, or microbial resistance. This has led to growing interest in herbal alternatives that offer effective relief with better safety and tolerability.⁴

Fig. 1: Mouth Ulcer

Hibiscus rosa-sinensis (Malvaceae) is a well-known medicinal plant used traditionally for its anti-inflammatory, antioxidant, antimicrobial, and wound-healing properties. Its bioactive components, including flavonoids, anthocyanins, and phenolic compounds, make it a promising candidate for treating oral lesions.^5,6

Fig. 2: Hibiscus rosa-sinensis leaves and flowers.

In the present study, a Hibiscus-based herbal gel was formulated using Hibiscus rosa-sinensis extract, honey, and peppermint oil. Honey enhances wound healing and provides antimicrobial protection, while peppermint oil contributes to pain relief and a soothing sensation. A mucoadhesive gel base was chosen for its ability to prolong contact time at the site of application, improving efficacy and user compliance.

The goal of this research is to formulate and evaluate a stable and effective herbal gel for the treatment of mouth ulcers, and to assess its physicochemical properties. This formulation may provide a natural and safer alternative to conventional ulcer therapies.

2. MATERIALS AND METHODS:

2.1 Materials:

Hibiscus rosa-sinensis extract was prepared in-house from leaves of the plant collected from the college botanical garden. Honey was purchased from the local market. All other chemicals like Peppermint oil (Mentha piperita), Carbopol 934, Propylene glycol, Glycerine, Triethanolamine, Methyl and Propyl parabens were purchased from Sudarshan Scientific Laboratories Limited, Nandgaon.

2.2 Extraction Procedure:

Recently harvested Hibiscus rosa-sinensis leaves and the flowers were carefully rinsed with distilled water to eliminate surface contaminants and carefully detached from the stems. The cleaned leaves were air-dried at ambient temperature in a well-ventilated, shaded area for 14 days to preserve their phytoconstituents. The dried leaves were then pulverised into a coarse powder using a mechanical grinder. A total of 50 g of the powdered material was subjected to solvent extraction using a hydroalcoholic mixture (Ethanol: Water, 70:30 ratio) in a Soxhlet apparatus. Prior to Soxhlet extraction, the plant material was macerated and shaken at room temperature for 1 hour to enhance solubilization of active constituents. After adding the washing solvent, the mixture was filtered with Whatman No. 1 paper and the collected filtrate was then concentrated with lowered air pressure. After extraction, the final solution was placed in amber-coloured, sterile containers and stored in the refrigerator until needed again.^7,8

2.3 Preparation of Herbal Gel:

A measured quantity of Carbopol 934 was dispersed in a predetermined volume of distilled water under continuous stirring to facilitate uniform hydration of the polymer. In a separate beaker, 5 mL of distilled water was heated mildly using a water bath, and the required amounts of methyl paraben and propyl paraben were dissolved to serve as preservatives. After cooling the solution to room temperature, propylene glycol was added as a humectant, followed by a suitable quantity of honey, incorporated for its therapeutic and flavour-enhancing properties. The pre-weighed quantity of Hibiscus rosa-sinensis extract was then added and mixed thoroughly. Peppermint oil was introduced dropwise to impart a soothing aroma and additional antimicrobial activity. The total volume of the formulation was adjusted to 20 mL using distilled water. As the stirring continued, the prepared phase was slowly added to the hydrated Carbopol 934 gel to ensure it was all mixed evenly. At the end, triethanolamine was dripped in drop by drop while stirring the mixture until its pH became suitable for application on the oral mucosa. Detailed formula is given in Table 1.^9,10,11,12

Fig. 3: Prepared mouth ulcer gel.

Table 1: Formulation of mouth ulcer gel

Ingredients	F1	F2	F3
Carbopol 940	0.20 gm	0.25 gm	0.30 gm
Triethanolamine	0.1 ml	0.1 ml	0.1 ml
Propylene glycol	1.5 ml	2 ml	2.5 ml
Methyl paraben	0.2 g	0.2 g	0.2 g
Propyl paraben	0.1 g	0.2 g	0.2 g
Hibiscus extract	5 ml	5 ml	5 ml
Honey	1 ml	1 ml	1 ml
Peppermint oil	0.5 ml	0.5 ml	0.5 ml
Distilled water	q s to 20 ml	q s to 20 ml	q s to 20 ml

3. EVALUATION PARAMETERS:

3.1 Physical Appearance:

Gel formulations were checked to see how they appeared, including colour and texture. They are used to check the initial acceptability and uniformity of the formulation.

3.2 pH Measurement:

The pH of each formula was tested with a digital pH meter that had been calibrated beforehand. Every time, a gram of gel was added to 100 mL of purified water and the pH was measured three times. By averaging the three readings together, the pH was finalised. To keep the formula suitable for oral mucosa, triethanolamine was added.¹³

3.3 Viscosity:

Viscosity was determined using a Brookfield Viscometer equipped with spindle number S64 (model LV-4). Measurements were taken at 10 RPM to assess the consistency and flow behaviour of the gel.¹⁴

3.4 Spreadability:

Spreadability was assessed by the static parallel‑plate technique. Approximately 2 g of gel was placed on a clean glass plate, covered with a second plate, and compressed with a 500 g weight for 1 min at 25 ± 2 °C. The weight was then removed, and the maximum diameter of the spread film was determined. The test was carried out three times, and the findings were presented as mean ± SD to check whether the gel consistency was acceptable for patients. By using the following formula, spreadability was determined.

Where, W is the applied weight (g), is the diameter of the spread gel film (cm) measured after compression, and is the spreading time (s, fixed at 60 s in this study).¹⁵

3.5 Extrudability:

Extrudability of the gel formulations was evaluated using a collapsible aluminium tube. A fixed amount of each formulation (approximately 10 g) was filled into separate tubes and sealed. A force was applied using a standard weight for 10 seconds to determine the amount needed to extrude a 0.5 cm ribbon of gel.¹⁶ We calculated extrudability with the following equation:

Applied Weight (g)

Extrudability (g/cm) = -----------------------------------

Length of gel extruded (cm)

3.6 Skin Irritation Test:

A skin irritation test was performed by applying a small quantity of the optimised gel on the inner forearm of healthy human volunteers. The site was observed for signs of redness, itching, or irritation for 24 hours. The absence of adverse reactions indicated biocompatibility and suitability for topical application.¹⁷

4. RESULTS AND DISCUSSION:

4.1 Physical Characteristics:

All prepared gels exhibited an aesthetically pleasing presentation: each batch possessed a uniform, air‑bubble‑free texture with no visible phase separation, coupled with a subtle yet distinct minty aroma that effectively masked any herbal notes. The consistent homogeneity across formulations indicates adequate dispersion of all excipients and active constituents, while the refreshing odour enhances patient acceptability for intra‑oral use.

4.2 pH:

The measured pH of all the formulated gels is shown in Table 2. The gels show pH in a mildly acidic zone that aligns closely with the physiological pH of healthy oral mucosa (≈ 5.5–7.0), thereby minimising the likelihood of stinging or tissue irritation on application to ulcerated sites. Maintaining this slightly acidic environment can also help inhibit opportunistic microbial growth without compromising patient comfort. Nonetheless, for highly sensitive users, a pH near the lower end of the acceptable spectrum may provoke transient tingling; routine monitoring and, if necessary, fine‑tuning with a mild buffering agent are advisable to keep the formulation comfortably within the optimal range for widespread oral use.

Table 2: pH of the formulated gels. (Mean ± SD, n = 3)

Formulation	pH values
F1	5.7 ± 0.34
F2	5.8 ± 0.56
F3	5.8 ± 0.67

4.3 Viscosity:

Rheological evaluation revealed a progressive increase in viscosity across the series (F1 < F2 < F3). Formulation F1 displayed a moderately viscous profile (≈ 2.1 × 10⁴ cP), providing adequate spreadability while maintaining mucosal adhesion. F2 showed an intermediate viscosity (≈ 3.8 × 10⁴ cP), balancing ease of application with residence time. In contrast, F3 exhibited a markedly higher viscosity of 5.43 × 10⁴ cP, conferring superior retention at the lesion site and thereby potentially prolonging drug–tissue contact. While this elevated viscosity enhances mucoadhesion, excessive thickness may impart a perceptible tackiness and hinder uniform spreading, which could detract from patient compliance. Optimising polymer concentration is therefore critical to achieving a rheological window that maximises therapeutic residence without compromising user acceptability.

4.4 Spreadability:

Spreadability was found to decrease progressively across the formulations in the order F1 > F2 > F3. Formulation F1 exhibited the highest spreadability, followed by F2 with moderate spreadability, while F3 showed the lowest spreadability among the three.

Table 3: Spreadability of Different Formulations (Mean ± SD, n = 3)

Formulation	Spreadability (g·cm/s)
F1	12.8 ± 0.45
F2	9.6 ± 0.38
F3	5.8 ± 0.67

4.5 Extrudability:

The extrudability of the formulations was found to be inversely proportional to their viscosity. The results are summarised in the table below:

Table 4: Extrudability of Gel Formulations (Mean ± SD, n = 3)

Formulation	Extrudability (g/cm)
F1	13.2 ± 0.41
F2	10.7 ± 0.36
F3	7.9 ± 0.52

Formulation F1 exhibited the highest extrudability due to its lower viscosity, allowing easier gel flow under applied pressure. Conversely, F3 showed the lowest extrudability, correlating with its higher viscosity and thicker consistency.

From the above results, formulation F2 is found to be optimised. F2 offers intermediate viscosity, which supports sufficient mucoadhesion and residence time without causing excessive thickness or tackiness like F3. Though lower than F1, F2 still maintains good spreadability, ensuring ease of application and uniform coverage. F2 extrudes well under moderate pressure, unlike F3, which may be harder to dispense due to its higher thickness.

4.6 Skin irritation test:

Formulation F2 was evaluated for dermal safety by applying a small quantity to the inner forearm of healthy human volunteers. No signs of redness, itching, swelling, or any other visible irritation were observed at the application site over the 24-hour observation period. These findings indicate that F2 is non-irritant and safe for topical use.

5. CONCLUSION:

The present study successfully developed and evaluated herbal mouth ulcer gels formulated with Hibiscus rosa-sinensis extract, honey, and peppermint oil using Carbopol 934 as a gelling agent. Among the three formulations tested, F2 emerged as the optimised formulation, exhibiting a balanced rheological profile with intermediate viscosity (~3.8×10⁴ cP), which ensured adequate mucoadhesion and prolonged residence time without compromising ease of application. The spreadability and extrudability results further confirmed that F2 provides uniform coverage and can be dispensed conveniently, critical for patient compliance. The pH of all formulations was maintained within the physiological range of the oral mucosa, minimising the risk of irritation. Importantly, skin irritation testing of F2 demonstrated its biocompatibility and safety for topical application. Overall, the optimised gel formulation F2 offers a promising, patient-friendly, and effective topical therapeutic option for managing mouth ulcers, combining the benefits of natural bioactives with suitable physicochemical properties. Future studies focusing on in vivo anti-ulcer efficacy and clinical evaluations are warranted to further substantiate its therapeutic potential.

6. ACKNOWLEDGEMENT:

The authors are grateful to Divine College of Pharmacy, Satana, for providing the necessary facilities, infrastructure, and support to carry out the present research work successfully. The guidance and encouragement extended by the institution were instrumental in the completion of this study.

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Received on 19.05.2025 Revised on 18.06.2025

Accepted on 09.07.2025 Published on 25.07.2025

Available online from July 31, 2025

Res. J. Pharma. Dosage Forms and Tech.2025; 17(3):167-171.

DOI: 10.52711/0975-4377.2025.00023

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