Formulation and Evaluation of Herbal Emulgel for the Management of Eczema

Eczema, commonly known as atopic dermatitis, is a chronic inflammatory skin condition characterized by disrupted epidermal barrier function and IgE-mediated hypersensitivity to environmental and dietary allergens.^[1] The terms eczema and dermatitis are often used synonymously, referring to a polymorphic inflammatory skin disorder characterized in its acute phase by erythema, vesicle formation, and blisters.^[2] The precise etiology of eczema remains incompletely understood; it is widely considered to result from complex interactions between genetic factors and environmental influences. Genetic predisposition, particularly mutations in the filaggrin (FLG) gene, leads to impaired skin barrier function and increased susceptibility to irritants and allergens. Variations in genes regulating T-cell activity, cytokine production, and IgE mediated immune responses particularly involving IL-4, IL-13, IL-31, and STAT3 pathways, contribute to the pathogenesis of the disease.^[3]

Treatment of eczema is multifaceted, with topical corticosteroids as the first-line anti-inflammatory therapy.^[4] However, prolonged use leads to side effects such as atrophy, rosacea, pigmentary changes, delayed wound healing, and worsening of skin infections.^[5]

Due to the limitations of conventional treatment, identifying safer, long-term strategies has become essential leading to increase in use of alternative and herbal therapies for management of atopic eczema.^[6]

Among various herbal therapies, Neem (Azadirachta indica) has been used widely in traditional system of medicine for the management of various diseases as the plant exhibits significant pharmacological activities such as anti-inflammatory, antibacterial, antioxidant and immunomodulatory effects. These pharmacological effects are primarily attributed to bioactive constituents such as nimbidin, nimbolide and azadirachtin which plays crucial role in modulating inflammatory responses. Furthermore, topical application of neem has been reported to alleviate pruritus and inflammation associated with eczema. In addition, Aloe vera (Aloe barbadensis Mill.) has gained considerable attention for its effectiveness in treating inflammatory skin conditions, owing to its soothing, moisturizing and wound-healing properties.^[7] These characteristics make both the plants promising candidates for the management of inflammatory skin disorders such as eczema.

Topical drug delivery involves the direct application of formulations to the skin, providing localized therapeutic effects and improved patient compliance. Among semisolid dosage forms, gels are widely preferred due to their ease of application and acceptability. However, conventional gels exhibit certain limitations such as incorporation of hydrophobic drugs, poor drug penetration and low retention at the application site.^[8]

Emulgel, a novel drug delivery system, combines the advantages of both emulsions and gels, thereby enhancing the solubility, stability and bioavailability of the therapeutic agents, particularly hydrophobic drugs. It offers improved skin penetration, controlled drug release and prolonged residence time making it a promising approach for topical drug delivery. Additionally, dermatological emulgels possess desirable properties such as non-greasy nature, ease of spreadability, emollient effect, ease of removal, non-staining nature, longer shelf life, and aesthetic appeal. ^[8,9]

Although several studies have reported the formulation of herbal emulgels for topical applications, limited research has focused on their use in the management of eczema. Furthermore, the optimization of surfactant ratios to enhance the rheological and physicochemical characteristics of herbal emulgels remains underexplored.

Therefore, the present study focuses on the development and evaluation of a polyherbal emulgel incorporating neem (Azadirachta indica) and aloe vera (Aloe barbadensis Mill), formulated with Carbopol 934 as a gelling agent and a combination of Tween 60 and Span 80 as surfactants; particular emphasis is placed on optimizing the surfactant ratio to improve rheological behaviour, spreadability and overall physicochemical properties for enhanced topical management of eczema.

MATERIAL AND METHODOLOGY

Materials

Carbopol 934, Tween 60, Span 80, Liquid paraffin, Propylene glycol and Triethanolamine were procured from school of pharmaceutical sciences, RIMT University, Punjab, India. Distilled water was used throughout the study.

Plant materials

Fresh neem leaves and aloe vera were collected from the medicinal plant garden at RIMT University, Punjab, India.

TABLE 1: LIST OF INSTRUMENTS AND EQUIPMENT USED

Methodology

Preparation of Plant extract ^[10]

• Prior to use, the collected neem leaves were washed to remove dirt and shade dried for 3-5 days to eliminate moisture content.
• The dried neem leaves were then finely powdered.
• 250 g of powdered neem was subjected to Soxhlet extraction using ethanol for 12 hours, until the solvent in the siphon tube became colorless.
• The resulting extract was concentrated using a water bath to obtain a crude extract, and stored in an airtight container at low temperature for further use.

FIGURE 1: SOXHLET APPARATUS USED FOR NEEM EXTRACTION

Preparation of emulgel

The emulgel was formulated in three steps^[11]

FIGURE 2: FLOWCHART OF EMULGEL FORMULATION PROCESS

1. Preparation of Emulsion

Oil Phase

• The oil phase was prepared by dissolving Span 80 in liquid paraffin.
• The mixture was heated on a water bath to approximately 70-75 °C.

Aqueous Phase

• The aqueous phase was prepared by dissolving Tween 60 and propylene glycol in distilled water.
• The solution was heated on water bath to approximately 70-75 °C.

Emulsion Formation

• After both phases were heated to 70 °C, the oil phase was slowly added to the aqueous phase with continuous stirring.
• Stirring was maintained until the mixture cooled down to room temperature, forming a stable emulsion.

2. Preparation of Gel Base^[12]

• Carbopol 934 was dispersed in distilled water with constant moderate stirring.
• The dispersion was allowed to swell overnight to ensure complete hydration.
• Triethanolamine was added to adjust the pH and to obtain a smooth, homogeneous base.

3. Incorporation of Herbal Extracts

• After cooling, measured quantities of neem and aloe vera extracts were incorporated into the emulsion with continuous stirring.

4. Preparation of Emulgel

• The herbal-loaded emulsion was slowly incorporated into the gel base in 1:1 ratio under continuous stirring.
• Stirring was continued until a smooth and homogeneous emulgel was obtained.

TABLE 2: COMPOSITION OF HERBAL EMULGEL FORMULATION

Evaluation of Emulgel formulation

• Physical characteristics

The prepared emulgel was inspected visually for color, appearance, phase separation, grittiness and consistency.

TABLE 3: PHYSICAL CHARACTERISTICS OF THE PREPARED EMULGEL

• pH Evaluation^[13]

pH is an important parameter for topical formulations, as it should be compatible with the skin to avoid irritation. Ideally the pH of the emulgel should be in the range  of 5-7 to mimic the normal skin conditions. Any significant deviation from this range may lead to skin irritation. The pH of the prepared emulgel formulations were determined using a digital pH meter.

TABLE 4: CHARACTERIZATION OF PREPARED EMULGEL FOR pH

All values represent mean ± standard deviations (SD), n=3

• Spreadability Studies^[14,15]

Spreadability of the prepared emulgel formulation was determined using the parallel plate method. A known quantity (0.5g) of emulgel was placed between two transparent plastic films. A weight of 250 g was placed over the upper film to allow uniform spreading of the formulation. After 1 minute, the diameter of the spread emulgel was measured. The experiment was performed in triplicate, and the average value was calculated .

TABLE 5: CHARACTERIZATION OF PREPARED EMULGEL FOR SPREADABILITY

All values represent mean ± standard deviations (SD), n=3

• Rheological Studies^[11,14]

Rheological studies focus on viscosity, a key property of fluids that measures their resistance to flow and is associated with the internal friction within the fluid. The rheological behaviour of the formulated emulgel was evaluated to determine its flow characteristics and viscosity profile. The viscosity of all prepared emulgel was measured using a Brookfield digital viscometer equipped with spindle no. LV4. Each sample was carefully transferred into sample container, ensuring the absence of air bubbles. The spindle (LV4) was immersed into the formulation up to the marked level and viscosity readings were recorded at different rotational speeds, namely 6, 12, 30 and 60 rpm. The corresponding viscosity values (in mPa.s) were recorded after stabilization at each speed. The obtained data were plotted and are shown in Figure 3.

FIGURE 3: RHEOLOGICAL BEHAVIOUR OF EMULGEL FORMULATION AT DIFFERENT ROTATIONAL SPEEDS

• Washability

The washability of the formulated emulgel was evaluated to determine its ease of removal from the skin surface after application. A small amount of the formulation was applied on the skin and allowed to remain for few minutes. The applied area was then washed with the tap water at room temperature without using any cleansing agent. The ease and extent of removal was observed visually. The formulation was evaluated for any residual film formation or difficulty in washing off. Good washability ensures patient compliance.

TABLE 6: CHARACTERIZATION FOR WASHABILITY OF PREPARED EMULGEL

• Stability Study

The prepared emulgel formulations were subjected to accelerated stability studies to evaluate their physical  stability studies under stress conditions. The study was carried out by storing the formulations in a hot air oven maintained at 50°C ± 2°C for a specified period of time. A known quantity of each formulation was placed in properly labelled, air tight containers and kept in oven. The samples were observed periodically for any changes in physical appearance, colour, phase separation, consistency and odour.

After exposure to elevated temperature, formulations were examined and compared with their initial properties. The stability study helps in predicting the shelf life of the formulation under normal storage conditions.

RESULT AND DISCUSSIONS

The herbal emulgel formulation containing neem and aloe vera for the treatment of eczema was successfully prepared using Carbopol 934 as the gelling agent. Five different formulations (F1,F2,F3,F4 and F5) were developed using varying concentrations of surfactants, namely Tween 60 and Span 80, to optimize the emulsion stability and drug delivery characteristics. All formulations were observed to be pale off-white to light greenish in appearance, with a smooth, homogeneous texture and a glossy finish indicating successful incorporation of both oil and aqueous phases without phase separation, as shown in Figure 4 and 5.

FIGURE 4: PREPARED EMULGEL FORMULATIONS F1-F4

FIGURE 5: PREPARED EMULGEL FORMULATION F5