Formulation and Evaluation of Pain Relief Roll-On Containing Diclofenac Sodium and Curcumin for Rheumatoid Arthritis

Rheumatoid arthritis is a chronic, progressive autoimmune inflammatory disorder that primarily affects synovial joints, leading to pain, swelling, stiffness, and eventual joint deformity¹ It is associated with systemic complications and significantly impacts the quality of life and daily activities of patients². The pathophysiology involves activation of immune responses and release of inflammatory mediators such as cytokines, prostaglandins, and enzymes that contribute to joint destruction^1,20 Conventional management mainly includes non-steroidal anti-inflammatory drugs (NSAIDs) like diclofenac sodium, which provide effective symptomatic relief by inhibiting cyclooxygenase (COX) enzymes and reducing prostaglandin synthesis³. However, long-term use of NSAIDs may result in adverse effects such as gastrointestinal irritation and cardiovascular risks^3,8. On the other hand, curcumin, a natural polyphenolic compound, has been widely reported for its anti-inflammatory and antioxidant properties^4,18 It acts by modulating multiple signaling pathways, including inhibition of NF-κB and other inflammatory mediators?. Studies on combined formulations of diclofenac sodium and curcumin have demonstrated enhanced therapeutic effectiveness due to their complementary mechanisms of action^5,7

Pathophysiology of Rheumatoid Arthritis

Fig. No. 1: Pathophysiology of Rheumatoid Arthritis

Topical Drug Delivery Systems -

Topical drug delivery systems have emerged as an effective alternative to conventional oral therapy, especially for localized conditions such as rheumatoid arthritis. These systems offer several advantages, including direct application at the site of inflammation, reduced systemic drug exposure, and minimized adverse effects. The effectiveness of topical delivery depends on the formulation design and the use of suitable excipients such as oils and penetration enhancers, which facilitate drug permeation through the skin?. Various studies have indicated that topical formulations containing anti-inflammatory agents can provide sustained drug release, improved bioavailability at the target site, and enhanced patient compliance?. Therefore, topical delivery systems represent a safe and efficient strategy for the treatment of inflammatory conditions.⁷

Fig. No. 2: Mechanism of Topical Drug Penetration

Roll-On Formulation:

Among the different topical dosage forms, roll-on formulations have gained increasing attention due to their convenience, portability, and user-friendly nature. The roll-on applicator allows uniform distribution of the formulation over the affected area without direct hand contact, thereby maintaining hygiene and reducing the risk of contamination. Studies on roll-on formulations have reported good physical stability, effective drug delivery, and high patient acceptability. Therefore, the development of a topical roll-on formulation containing diclofenac sodium and curcumin can be considered a novel and effective approach for the management of rheumatoid arthritis^6,11,12

MATERIALS AND METHODS:

Diclofenac sodium was gifted from Rajgad Dnyanpeeth’s College of Pharmacy Bhor. Curcumin extract was procured from Aushadhi Herbal. Castor oil, coconut oil, sesame oil, and sunflower oil used in the formulation were cold-pressed oils obtained from Gradient Chemicals. Glycerin and Ethanol were procured from Gradient Chemicals.

All the materials used were of analytical grade and were used as received without further purification.

Other Excipients: ^13,41

1. Castor Oil:

Family: Euphorbiaceae

Category: Oil base

Function: Acts as vehicle and increases viscosity

Fig. No. 3: Castor oil

2. Coconut Oil

Family: Arecaceae

Category: Emollient

Function: Moisturizes skin and improves spreadability

Property: Soothing, anti-inflammatory, skin-friendly

Fig. No. 4: Coconut oil

3.Sesame Oil

Family: Pedaliaceae

Category: Penetration enhancer

Function: Enhances drug absorption through skin

Property: Rich in antioxidants, good permeation ability

Fig. No. 5: Sesame oil

4.Sunflower Oil

Family: Asteraceae

Category: Vehicle

Function: Provides base for formulation

Property: Light, non-greasy, easily absorbable                                     

Fig. No. 6: Sunflower oil

5.Menthol

 Family: Lamiaceae

Category: Cooling agent

Function: Provides cooling sensation and analgesic effect

Property: Counter-irritant, soothing, refreshing

Fig. No. 7: Menthol

6.Glycerine

 Category: Humectant

 Function: Retains moisture and improves hydration

 Property: Hygroscopic, moisturizing, skin softening

Table No.1: Formulation of Roll-On

METHODS:

Accurately weighed quantity of diclofenac sodium and curcumin was taken. The oils (castor oil, coconut oil, sesame oil, and sunflower oil) were mixed together to form the oil base. Menthol was added to the oil base and mixed properly until completely dissolved. Diclofenac sodium and curcumin were then incorporated into the mixture with continuous stirring to obtain a uniform dispersion. Glycerin was added to improve consistency and smoothness of the formulation. Ethanol was added as a solvent to adjust the final volume and enhance penetration. The formulation was mixed thoroughly using mechanical shaking to ensure homogeneity. The prepared formulation was filled into roll-on bottles and stored for further evaluation.¹²

EVALUATION PARAMETERS: ^13,14

1. Physical Appearance: The prepared formulations were visually inspected for color, clarity, and overall appearance by placing the formulations against a black and white background under normal light conditions.

2. Color and Odor: The color and odor of the prepared formulations were evaluated visually and by smelling the formulation to determine acceptability and uniformity.

3. Homogeneity: The formulations were checked for homogeneity by visual inspection to ensure uniform distribution of ingredients and absence of lumps or phase separation.

4. Texture: The texture of the formulation was evaluated by applying a small quantity on the skin surface and observing smoothness and grittiness.

5. pH: The pH of the formulation was determined using a calibrated digital pH meter. The electrode was immersed in the formulation and the pH was recorded at room temperature..

6. Viscosity: The viscosity of the formulations was measured using a Brookfield viscometer at room temperature. The Spindle no. 64 is used for determination of viscosity of roll-on. The spindle was immersed into the formulation and readings were recorded.

7. Spreadability: Spreadability was determined by applying the formulation on the skin surface and observing the ease of spreading and uniform application.

8. Leakage Test: The formulation was filled into roll-on containers and stored in upright and inverted positions. The containers were observed for any leakage over a specified period.

9. Skin Irritation Test:

A small quantity of formulation was applied on a small area of skin and observed for redness, itching, irritation, or any allergic reaction after application.

RESULTS AND DISCUSSION:

1. UV Spectrophotometric Analysis

The UV spectrum of diclofenac sodium and curcumin showed characteristic absorption peaks in the UV region. Diclofenac sodium exhibited absorption maxima at 280 nm. The observed values were found to be within the standard reported range, confirming the identity and purity of the drugs. The obtained spectra indicated suitability of the drugs for further formulation and analytical studies.

Fig. No.8: UV spectrum of Diclofenac Sodium

2. FT-IR Spectroscopic Analysis

Fourier transform infrared (FT-IR) spectra were obtained via Shimadzu IR to understand the interactions between the physical mixture of drug and excipients, which are used in the formulation of roll-on. The spectra were observed in the region from 4000 to 400 cm^-1. The spectra of the pure drug (Diclofenac Sodium) and the physical mixture of drug and excipients are given in Fig. No. 9. The spectral interpretation of the drug and excipient mixture of the formulation is given in Table No. 2. Spectral analysis revealed that there was no interaction between the drug and excipients and that they were compatible with each other.

Fig. No.9 : FT-IR Graph of Diclofenac Sodium and Physical Mixture of Diclofenac Sodium with Curcumin

Table No.2: Interpretation of FT-IR Analysis

3. Physical Appearance:

The prepared formulations were visually inspected for color, clarity, and overall appearance. All formulations showed uniform appearance.

4. Color and Odor:

The formulations exhibited a characteristic yellow color due to curcumin and a pleasant odor due to menthol.

5. Homogeneity:

The formulations were evaluated for uniform distribution of ingredients and were found to be homogeneous with no lumps.

6.  Texture:

The texture of the formulation was assessed by applying it on the skin and was found to be smooth and non-gritty.

7. pH:

The pH of the formulation was determined using a pH meter and was found to be within range of 5.5 to 6.5, suitable for skin application.

8. Viscosity:

The viscosity of the formulations was evaluated using a Brookfield viscometer. F1 showed low viscosity, F2 showed moderate viscosity, and F3 showed high viscosity. F2 was found to have optimum viscosity suitable for application.

9. Spreadability:

The formulations were tested for ease of spreading on the skin and showed good Spreadability.

10. Leakage Test:

The formulation was filled in a roll-on container and observed for leakage. No leakage was observed.

11. Skin Irritation Test:

The formulation was applied on a small area of skin and no irritation or redness was observed.

Table No.3: Evaluation Parameter of Roll-On