Formulation and In Vitro Evaluation of a Self-Emulsifying Drug Delivery System of Diclofenac Sodium

Oral drug delivery remains the most preferred route of administration due to its convenience, patient compliance, and cost effectiveness ^[1]. However, a major challenge in oral drug delivery is the poor aqueous solubility of many therapeutic agents, which leads to low dissolution rates and reduced bioavailability ^[2]. With the advancement of drug discovery, a significant number of newly developed drugs fall under Biopharmaceutics Classification System (BCS) Class II, characterized by high permeability but poor solubility ^[3]. For such drugs, absorption is primarily limited by the dissolution step in the gastrointestinal tract ^[4]. Diclofenac Sodium is a widely used non-steroidal anti-inflammatory drug (NSAID) prescribed for the management of pain, inflammation, and rheumatic disorders ^[5]. Despite its strong therapeutic efficacy, its oral bioavailability is limited due to poor water solubility, variable gastrointestinal absorption, and extensive first-pass metabolism ^[6]. Conventional oral dosage forms often require higher doses to achieve the desired therapeutic effect, which increases the risk of gastrointestinal irritation and other adverse effects ^[7]. To overcome these limitations, lipid-based drug delivery systems have gained considerable attention ^[8]. Among them, Self-Emulsifying Drug Delivery Systems (SEDDS) represent a promising approach to enhance the solubility and oral bioavailability of poorly water-soluble drugs. SEDDS are isotropic mixtures of oils, surfactants, and co-surfactants that spontaneously form fine oil-in-water emulsions upon mild agitation in gastrointestinal fluids ^[9]. The formation of small droplet sizes significantly increases the surface area available for drug dissolution, thereby improving absorption ^[10]. The present research focuses on the formulation and in vitro evaluation of a SEDDS containing Diclofenac Sodium with the aim of improving its solubility, dissolution behavior, and overall oral performance ^[11]. By optimizing the formulation components and evaluating key physicochemical parameters, this study seeks to develop a stable and efficient self-emulsifying system suitable for oral administration ^[12]. Diclofenac Sodium has been extensively used in clinical practice for decades; however, its therapeutic potential through oral administration is compromised by poor aqueous solubility and gastrointestinal side effects ^[13]. Conventional tablets and capsules show delayed onset of action and inconsistent plasma drug levels, particularly in patients with altered gastrointestinal physiology ^[14]. Several formulation strategies such as solid dispersions, microspheres, nanoparticles, and transdermal systems have been explored to improve the performance of Diclofenac Sodium. Although these approaches have shown varying degrees of success, many of them involve complex manufacturing processes, high production costs, or stability issues ^[15]. SEDDS offer a simpler and more practical alternative by maintaining the drug in a solubilized state throughout its passage in the gastrointestinal tract. The ability of SEDDS to form fine emulsions in situ eliminates the need for the drug to dissolve before absorption. In addition, lipid-based systems may promote lymphatic transport, thereby reducing first-pass hepatic metabolism and improving systemic availability ^[16]. Considering these advantages, the development of a SEDDS formulation for Diclofenac Sodium represents a rational and effective approach to address its biopharmaceutical limitations. This background forms the foundation for the present research work. Several studies have demonstrated the effectiveness of self-emulsifying and microemulsion-based systems in enhancing the solubility and bioavailability of Diclofenac Sodium. Previous research has shown that SEDDS formulations significantly improve dissolution rates compared to conventional dosage forms. Studies involving topical, transdermal, injectable, and oral SEDDS of Diclofenac Sodium reported improved drug release, better stability, and enhanced therapeutic outcomes. Researchers have also highlighted the role of appropriate oil selection, surfactant concentration, and pseudo-ternary phase diagram construction in achieving stable and efficient self-emulsifying systems. Recent investigations emphasized the importance of droplet size, zeta potential, and thermodynamic stability in predicting in vitro and in vivo performance ^[17]. Although many studies explored alternative delivery routes, comparatively fewer reports focus on simple oral SEDDS formulations optimized for routine clinical use with minimal surfactant-related toxicity ^[18]. Overall, the literature confirms that SEDDS is a promising delivery platform for Diclofenac Sodium, but further systematic formulation optimization and in vitro evaluation are required to ensure stability, safety, and reproducibility.

Despite extensive research on Diclofenac Sodium delivery systems, certain gaps remain:

• Limited studies focus on simple oral SEDDS formulations optimized specifically for Diclofenac Sodium.
• Many reported formulations emphasize either solubility enhancement or stability, but not both simultaneously.
• Inadequate comparative evaluation of self-emulsification efficiency, droplet size distribution, and thermodynamic stability under simulated gastrointestinal conditions.
• Insufficient emphasis on formulation simplicity and scalability for industrial application.

These gaps indicate the need for a systematically designed SEDDS formulation that balances solubility enhancement, stability, and practical feasibility

MATERIAL AND METHOD

Table 1: List of drugs, oil, surfactant, co- surfactant:

Experimental Work

Preformulation Studies of Pure Drug

Identification of Drug

Pre-formulation study is a pharmaceutical and analytical investigation carried out prior to and in support of formulation development of a dosage form of the drug substance. It provides the fundamental understanding necessary to develop a suitable formulation for preclinical, clinical, and therapeutic use. Pre-formulation yields information about the physicochemical, structural, and thermal properties of the drug substance, which is essential for designing a stable and effective dosage form. Hence, the following studies were performed on the obtained sample of Diclofenac Sodium.

Melting Point Determination

The melting point of Diclofenac Sodium was determined by the capillary method. In this method, a few crystals of the compound were filled in a thin-walled capillary tube (10–15 cm long, 1 mm internal diameter) sealed at one end. The tube was attached to a thermometer and gradually heated in a controlled melting point apparatus until complete melting of the sample was observed. The temperature range at which the drug melted was noted as the melting point.

• The melting point of Diclofenac Sodium was found to be 284.5 °C, which is in agreement with reported literature values, thereby confirming its identity and purity.

FT-IR Spectral Analysis

Fourier Transform Infrared (FT-IR) Spectroscopy was employed to characterize the functional groups and confirm the structure of Diclofenac Sodium. The analysis was carried out using the KBr pellet method. About 10 mg of the drug sample was triturated with dried potassium bromide and compressed into a transparent pellet using a hydraulic press under high pressure. The prepared disc was scanned in the spectral region 4000–400 cm⁻¹ under identical conditions. These peaks confirmed the presence of the functional groups of Diclofenac Sodium and validated the drug sample.

FIG 1: FT IR GRAPH

Differential Scanning Calorimetry (DSC)

Differential Scanning Calorimetry (DSC) was performed to evaluate the thermal behavior and crystalline nature of Diclofenac Sodium. DSC measures the difference in the heat flow between the sample and a reference as a function of temperature.

During heating, Diclofenac Sodium exhibited a sharp endothermic peak corresponding to its melting point at ~285 °C, confirming its crystalline nature and purity. The absence of additional peaks indicated no polymorphic transitions or degradation during the heating process.

FIG 2: DSC GRAPH

Calibration Curve of Diclofenac Sodium

Preparation of Stock Solution

An accurately weighed quantity of 25 mg of Diclofenac Sodium was transferred into a clean and dry 25 ml volumetric flask. The drug was dissolved and the volume was made up to the mark with pH 6.8 phosphate buffer to obtain a solution of 1000 µg/ml concentration. From this solution, 2.5 ml was withdrawn and diluted to 25 ml with the same buffer to yield a working stock solution of 100 µg/ml concentration.

Determination of λmax

For the determination of the maximum absorbance wavelength (λmax), the stock solution (100 µg/ml) was scanned in the UV-Visible spectrophotometer within the wavelength range of 200–400 nm using pH 6.8 phosphate buffer as a blank. Diclofenac Sodium exhibited a characteristic absorption maximum (λmax) at 276 nm in pH 6.8 phosphate buffer.

Preparation of Seral Dilutions

From the working stock solution (100 µg/ml), a series of dilutions were prepared to obtain concentrations of 2, 4, 6, 8, and 10 µg/ml using pH 6.8 phosphate buffer as the diluent. The absorbance of each solution was measured at 276 nm against a buffer blank using the UV-Visible spectrophotometer.

Table 2: Concentration and Absorbance Values

Result

A linear relationship was observed between the absorbance and concentration of Diclofenac Sodium in the selected concentration range. The calibration curve obeyed Beer–Lambert’s law within the range of 2–10 µg/ml with λmax at 276 nm.

Fig 3: Concentration VRS Absorbance Graph

Solubility of Drug in Oils, Surfactants, and Co-surfactants

Poor aqueous solubility of Diclofenac Sodium (DS) is a major rate-limiting step in its oral absorption. Hence, determination of solubility in various oils, surfactants, and co-surfactants was carried out to identify suitable components for the formulation of SEDDS.

METHODOLOGY

1. Selection of Oil Phase
   • The oil phase was selected based on maximum solubility of Diclofenac Sodium.
   • Various oils such as Coconut Oil, Oleic Acid, and Soybean Oil were screened.
2. Selection of Surfactants
   • Surfactants were chosen on the basis of their HLB value, ability to solubilize DS, and safety (non-toxic nature).
   • Surfactants evaluated were Tween-80, Labrasol, and Cremophor RH.
3. Selection of Co-surfactants
   • Co-surfactants were screened based on their ability to form stable, transparent emulsions with minimum concentration.
   • The shortlisted co-surfactants were Polyethylene Glycol 400 (PEG 400), Propylene Glycol, and Transcutol.

Experimental Procedure

• An excess amount of Diclofenac Sodium (10 mg) was added to 4 mL of each selected oil, surfactant, and co-surfactant in screw-capped vials.
• The mixtures were vortexed thoroughly to facilitate solubilization.
• The vials were kept at room temperature until equilibrium was achieved.
• The solubility was assessed based on time required for complete dissolution and clarity of solution.

Table 3: Solubility of Diclofenac Sodium in Different Oils, Surfactants, and Co-surfactants

Table 4: Solubility of Diclofenac Sodium in Different Oils, Surfactants, and Co-surfactants