INTRODUCTION:

Acne vulgaris is a chronic dermatological disorder characterized by follicular hyperkeratosis, excess sebum production, Cutibacterium acnes proliferation, and inflammation, leading to various skin lesions and reduced quality of life ¹.

Azelaic acid (AzA), a naturally occurring dicarboxylic acid, is widely used in the treatment of acne due to its antimicrobial, anti-inflammatory, antioxidant, and anti-keratinizing properties. It effectively inhibits the growth of C. acnes and reduces abnormal keratinization, thereby preventing come done formation ². However, the clinical performance of azelaic acid is often hindered by its poor aqueous solubility and limited permeability across the stratum corneum, which restricts its bioavailability at the target site ³.

Conventional topical formulations such as creams, ointments, and gels often exhibit limitations including poor drug penetration, low retention time, and inadequate controlled release ⁴. Although advanced delivery systems such as microemulsions, liposomes, and hydrogels have been developed to overcome these challenges, they typically fail to simultaneously provide both hydrophilic and lipophilic environments required for optimal drug delivery⁵. Bigels, which are biphasic systems composed of both hydrogel and organogel networks, have emerged as promising drug delivery platforms. They combine the advantages of both systems, offering improved drug stability, enhanced penetration, controlled release, and better patient acceptability due to their non-greasy and easily spreadable nature ⁶.

However, despite these advantages, limited studies have explored the incorporation of azelaic acid into bigel systems for topical acne treatment. Therefore, the present study aims to develop and evaluate azelaic acid-loaded bigel formulations to enhance drug delivery, improve physicochemical properties, and achieve better therapeutic outcomes in acne management ^7,8.

MATERIAL AND METHODS:

Azelaic acid (purity ≥ 98%) was sourced from S G Overseas, Surat. Lecithin was obtained from Nishall Traders, Surat. Carbopol 934, propylene glycol, and glycerine were procured from Aether Industries Ltd. and PJS Chemicals, Surat. Triethanolamine was sourced from Kavya Pharma, Vapi. All chemicals were of analytical grade.

Preformulation study of Azelaic acid:

1. Organoleptic Property:

The physical examination involved assessing the organoleptic properties of azelaic acid, including its colour, odour and overall appearance ⁹.

2. Determination of Melting point:

The melting point of Azelaic acid was determined by capillary method ¹⁰.

3. Fourier Transform Infrared Spectroscopy of Azelaic acid:

Fourier-transform infrared spectroscopy (FTIR) is employed for compound identification through the absorption of infrared radiation. This technique reveals the functional groups present in the drug¹¹. For analysis, the drug is mixed with potassium bromide (KBr) and compressed into pellets. The FTIR spectra are recorded over a wavenumber range of 400 cm^-1 to 4000 cm^-1with a resolution of 1 cm^-1.

METHOD OF PREPARATION OF BIGEL:

Method of Preparation of Bigel:

The Bigel was developed through a three-step process: formulation of hydrogel, preparation of organogel, and combination of both gels in specified ratios. The final product incorporated 5% w/w Azelaic acid ¹².

1. Preparation of Hydrogel:

Hydrogel formulations were developed using varying concentrations of HPMC K4M (0.5%–2% w/v). The polymer was slowly dispersed in 25 ml of distilled water with continuous stirring to prevent lump formation. The dispersion was left to hydrate and swell for 24 hours at room temperature to obtain a transparent gel ¹³.

Table 1: Composition of Hydrogel Formulations

Formulation Code	HPMC K4M (% w/v)	Distilled Water (mL)
HG1	0.5	25
HG2	1.0	25
HG3	1.25	25
HG4	1.5	25
HG5	2.0	25

2. Preparation of Organogel:

Organogel was prepared in three stages involving formation of oil phase and aqueous phase, followed by their controlled mixing ^14-15.

i. Oil Phase Preparation:

Soya lecithin was dissolved in isopropyl myristate (IPM) under continuous stirring. Sodium benzoate was added as a preservative. The mixture was stored at ambient temperature for 24 hours to allow stabilization.

ii. Aqueous Phase Preparation:

Poloxamer 407 was dispersed in cold distilled water and refrigerated (4°C) for 24 hours after initial stirring and 1-hour soaking. Sodium benzoate was added to preserve the formulation.

iii. Formation of Organogel:

The oil phase was gradually added into the cold aqueous phase with continuous stirring to produce a uniform organogel.

Table 2: Organogel Composition

Formulation Code	IPM (mL)	Lecithin (mL)	Poloxamer 407 (g)	Preservative
OG1	12.5	1.21	3.00	Sodium benzoate
OG2	12.5	1.50	3.75	Sodium benzoate
OG3	12.5	2.00	4.00	Sodium benzoate
OG4	12.5	2.00	4.00	Sodium benzoate
OG5	12.5	2.00	4.50	Sodium benzoate

Table 3: Final Bigel Formulations with 5% Azelaic Acid

Formulation Code	Azelaic Acid (%)	Hydrogel (%)	Organogel (%)	OG: HG Ratio
BG1	5	50	46	1:1
BG2	5	54	42	1:1
BG3	5	58	38	1:1
BG4	5	62	34	1:1
BG5	5	66	30	2:1

Preparation of Azelaic Acid-Loaded Bigel:

Bigel was prepared by mixing optimized quantities of hydrogel and organogel in different ratios ranging from 1:1 to 2:1 (hydrogel: organogel). Azelaic acid (5% w/w) was first dissolved in a minimal volume of glycerine and then incorporated into the gel mixture under continuous stirring until a homogenous formulation was achieved ¹⁶.

EVALUATION:

Physical appearance:

The physical characteristics of the formulated gels were assessed through visual inspection, focusing on aspects such as consistency, colour, texture, spreadability in the skin, washability and any greasiness.

pH:

The pH of all the prepared gels was determined using a digital pH meter. The electrode was gently placed on the surface of the prepared gel and allowed to equilibrate for 1 minute, after which the reading was recorded. Maintaining the pH close to the physiological skin tolerance range is important to ensure skin compatibility, minimize irritation, and improve patient comfort and safety during topical application.

Viscosity:

Brookfield viscometer was used for determination of viscosity of prepared gels. A 50 ml beaker was filled with the samples that will be examined. Spindle number L3 was used to measure the samples' viscosity. For each sample, the test was conducted three times, and the mean value was determined¹⁸. The angular velocity was maintained at 30 rpm for the measurement, which was conducted at room temperature.

Spreadability:

The spreadability of the formulated batches was determined using two glass plates and a weight. A 1 cm circle was pre-marked on one of the glass plates, where 0.5 grams of gel was applied. Another glass plate of the same size was placed over the gel, and a 1000 g weight was positioned on the upper plate for 5 minutes. The resulting increase in the gel's diameter, due to its spreading, was then measured.

Extrudability Study:

This evaluation assessed the ease of extruding the bigel from a tube. A specific weight was applied to extrude a 0.5 cm ribbon of gel within 10 seconds. A higher quantity of gel extruded indicated better extrudability. Extrudability was calculated using the formula:

Extrudability = Applied weight to extrude bigel from tube (gm)/ Area (cm²)

Drug Content:

Drug content was found by following method, 1g of bigel sample was taken and dissolved in 10ml of methanol followed by sonication for 15 minutes. The solution obtained was filtered and diluted to bring it within the calibration curve range. The drug concentration of sample was determined by UV method¹⁹. Drug content is a quotient, expressed in percent, of amount of azelaic acid measured in bigel and that actually added into the bigel.

RESULT AND DISCUSSION:

Preformulation study of Azelaic acid:

1. Organoleptic Properties:

Azelaic acid appeared as a white to off-white crystalline powder with no characteristic odour. These attributes are in alignment with pharmacopeial descriptions and confirm the identity and purity of the drug substance.

2. Melting Point Determination:

The melting point of azelaic acid was observed at 109°C, which is within the reported range (106–110°C), indicating its purity and absence of significant impurities.

3. Fourier Transform Infrared Spectroscopy of Azelaic acid:

FTIR was performed for Azelaic acid which is shown in figure 1 and interpretation of FTIR peaks is shown in Table 4.

Figure 1: FTIR of azelaic acid

Table No. 4 Characteristic peaks of Azelaic acid

Standard range	Obtained range	Functional group
2950-2840	2953.72	-C-H stretch
2900-2800	2851.10	-C-H-O aldehyde
1700-1500	1698.74	C=O amide
1480-1440	1468.16	CH₂bend

Physical Appearance:

The gel was white to pale yellow in colour and displayed a homogenous appearance, indicating a uniform distribution of components. It had a gel like consistency, which made it easy to apply and adhere to the skin. The gel washed off easily without leaving a sticky or greasy residue, though it was mildly greasy, likely due to the presence of lecithin.

pH:

Since the pH was within the range that is considered acceptable in topical applications, it would not irritate the skin. The prepared gels pH is shown in Table 5.

Table 5: Results of pH

Formulation code	pH (Mean ± SD)
BG1	6.6 ± 0.1
BG2	6.8 ± 0.2
BG3	7.1 ± 0.1
BG4	6.6 ± 0.2
BG5	6.5 ± 0.2

Viscosity:

A clear decreasing trend in viscosity was observed from BG1 (4550 cps) to BG5 (3750 cps). This can be attributed to the reduction in organogel concentration, which lowers the internal structural resistance of the system.Higher organogel content (BG1) resulted in increased viscosity due to stronger network formation, whereas lower organogel content (BG5) produced a less rigid structure, improving flow properties.This demonstrates that polymer–lipid balance plays a crucial role in controlling rheological behavior of bigels.

Table 6: Result of viscosity of formulated bigel

Formulation code	Viscosity (cps)
BG1	4550 ± 0.02
BG2	4350 ± 0.01
BG3	4150 ± 0.03
BG4	3900 ± 0.01
BG5	3750 ± 0.02

Spreadability:

Among all the formulations, BG5 exhibited the highest spreadability, indicating superior ease of application and better patient acceptability. This may be attributed to the lower proportion of the organogel phase (30%) and the higher hydrogel-to-organogel ratio (2:1), which reduced the internal structural resistance of the bigel system and consequently decreased its viscosity. An inverse relationship was observed between viscosity and spreadability, wherein the lower viscosity of BG5 contributed to enhanced spreadability, thereby making it the optimized formulation.

Extrudability:

The extrudability of the developed bigel formulations was assessed to determine ease of application. BG5 showed the highest extrudability, whereas BG1 exhibited the lowest. This may be attributed to the lower organogel concentration in BG5 (30%), which reduced viscosity and improved extrusion. The results further confirmed an inverse relationship between viscosity and extrudability.

Drug content:

The drug content of the optimized bigel formulation (BG5) was found to be 91.2% ± 1.25%, indicating satisfactory incorporation and uniform distribution of azelaic acid.

CONCLUSION:

In the present study, five azelaic acid-loaded bigel formulations (BG1 to BG5) were successfully prepared and evaluated for key physicochemical parameters, including pH, viscosity, spreadability, extrudability, and drug content. All formulations exhibited an acceptable pH range (6.5–7.1), indicating their suitability for topical application.

Viscosity analysis revealed that BG1, containing the highest proportion of organogel (46%), showed the highest viscosity (4550 ± 0.02 cps), resulting in lower spreadability and extrudability. In contrast, BG5, with the lowest organogel concentration (30%), exhibited the lowest viscosity (3750 ± 0.02 cps) along with the highest spreadability and extrudability, indicating superior ease of application and better patient compliance.

Drug content analysis confirmed satisfactory incorporation of azelaic acid, with BG5 showing 91.2% ± 1.25%, indicating uniform drug distribution. Based on the overall evaluation, BG5 was identified as the optimized formulation due to its favourable balance of acceptable pH, low viscosity, high spreadability, superior extrudability, and adequate drug content. Therefore, BG5 may be considered a promising patient-friendly topical bigel system for effective azelaic acid delivery in acne management.

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Received on 14.04.2025 Revised on 20.08.2025

Accepted on 06.11.2025 Published on 03.04.2026

Available online from April 06, 2026

Research J. Pharmacy and Technology. 2026;19(4):1765-1769.

DOI: 10.52711/0974-360X.2026.00253

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