Formulation and Evalution of Clindamycin Gel

Acne vulgaris is one of the most common dermatological disorders, affecting millions of individuals worldwide, particularly adolescents and young adults. It is a multifactorial skin disease characterized by inflammation of the pilosebaceous units, leading to the formation of comedones, papules, pustules, and in severe cases, cysts and nodules. The primary causative agent involved in acne pathogenesis is Propionibacterium acnes, an anaerobic Gram-positive bacterium that colonizes the sebaceous follicles. Topical therapy remains the cornerstone for treating mild to moderate acne due to its localized action, reduced systemic side effects, and improved patient compliance. Among the various topical agents, Clindamycin—a lincosamide antibiotic—has proven effective in suppressing P. acnes by inhibiting bacterial protein synthesis through binding to the 50S ribosomal subunit. Formulating Clindamycin into a topical gel provides several advantages over other dosage forms such as creams or lotions. Gels are non-greasy, have a cooling effect upon application, and allow for better drug penetration through the skin. Moreover, they offer good spreadability, patient acceptability, and controlled drug release. The current study aims to formulate a stable and effective Clindamycin gel using Carbopol 940 as the gelling agent, along with other excipients to enhance stability, skin penetration, and antimicrobial efficacy. The formulation is evaluated for key parameters such as pH, viscosity, drug content, spread ability, and in vitro drug release to ensure optimal therapeutic performance.

Profile of Formulation Ingredients⁴:

Clindamycin Phosphate

Role: Active Pharmaceutical Ingredient (API)

Function: Lincosamide antibiotic; inhibits protein synthesis in Cutibacterium acnes. Provides antimicrobial and anti-inflammatory action for acne treatment.

Concentration: Typically, 1% or 2% in the gel formulation, depending on the product.

2. Purified Water

Role

Function: Acts as the main solvent and carrier for all water-soluble ingredients. Ensures the formulation is smooth, stable, and skin compatible.

Concentration: Usually, a significant part of the formulation (often 60 80%)

3.Glycerin

Role: Humectant / Moisturizer

Function: Retains moisture on the skin and prevents dryness. Enhances skin feel and helps balance the drying effect of ethanol and carbomer.

4.Propylene Glycol

Role:  Penetration Enhancer / Humectant

Function: Enhances percutaneous absorption of clindamycin. Also acts as a solvent and moisturizer, improving skin hydration.

 5.Carbomer 940 Role: Gelling Agent

Function: Provides gel structure and viscosity. Ensures uniform distribution of the API and improves spread ability.

6. Triethanolamine

Role: pH Adjuster / Neutralizer

Function: Used to neutralize the acidic carbomer, forming the gel matrix. Also helps maintain formulation pH within a skin compatible range (≈5.5–6.5)                                                           

7.Methylparaben

Role: Preservative

Function: Prevents microbial growth in the formulation, enhancing product stability and safety during storage and use.

8. Ethanol

Role: Antiseptic solvent    

Function: Ethanol acts as a solvent, helping to dissolve clindamycin phosphate and other ingredients to form a stable and uniform gel.

1. Clindamycin Phosphate

Role: Active Pharmaceutical Ingredient (API) 

Function: Lacosamide antibiotic; inhibits protein synthesis in Cutibacterium acnes. Provides antimicrobial and anti-inflammatory action for acne treatment. 

Concentration: Typically, 1% or 2% in the gel formulation, depending on the product.

2. Purified Water

Role: Solvent & Base 

Function: Acts as the main solvent and carrier for all water-soluble ingredients. Ensures the formulation is smooth, stable, and skin compatible. 

Concentration: Usually, a significant part of the formulation (often 60 80%).

3. Glycerine  

Role:  Humectant / Moisturizer 

Function:  Retains moisture on the skin and prevents dryness. Enhances skin feel and helps balance the drying effect of ethanol and carbomer.

4.  Propylene Glycol   

Role:  Penetration Enhancer / Humectant 

Function:  Enhances percutaneous absorption of clindamycin. Also acts as a solvent and moisturizer, improving skin hydration.

5.  Carbomer 940   

Role:  Gelling Agent 

Function:  Provides gel structure and viscosity. Ensures uniform distribution of the API and improves spread ability.

6.  Triethanolamine   

Role:  pH Adjuster / Neutralizer 

Function:  Used to neutralize the acidic carbomer, forming the gel matrix. Also helps maintain formulation pH within a skin compatible range (≈5.5–6.5).

7.  Methylparaben   

Role:  Preservative 

Function:  Prevents microbial growth in the formulation, enhancing product stability and safety during storage and use.

8. Ethanol

Role: Antiseptic Solvent 

Function: Acts as a solvent, helping to dissolve clindamycin phosphate and other ingredients to form a stable and uniform gel.

EXPERIMENTAL WORK:

Carbopol 940 was used as the gelling agent, dispersed in purified water and allowed to swell for several hours to form the gel base.

Clindamycin phosphate was dissolved in water and incorporated into the gel base along with preservatives (methylparaben and propylparaben) dissolved in propylene glycol. The gel was neutralized using triethanolamine to adjust the pH to 5.5–6.0, which activated gel formation. The final gel was evaluated for pH, viscosity, spreadability, drug content, and in vitro drug release using standard methods. Stability studies were conducted at different storage conditions to assess the formulation's physical and chemical stability over time.

METHODOLOGY:

The chemical and reagents apply from Delight college of pharmacy Koregaon Bhima, Pune. Maharashtra, India 412216.

1. Preparation of Active Ingredient Solution:

• Dissolve Clindamycin phosphate (0.3 g) in purified water to create a homogeneous solution. This serves as the active pharmaceutical ingredient for acne treatment.

2. Gel Base Preparation:

• In a separate container, mix Carbomer 934 (0.6 g) with purified water (21.95 g) while stirring to create a gel base. Allow the Carbomer to hydrate and thicken the mixture, forming the gel's consistency.

3. Addition of Humectants and Solvents:

• Add Glycerin (3 g) as a humectant to retain moisture in the skin, followed by Propylene glycol (2 g) to serve as a solvent and penetration enhancer. Additionally, include Ethanol (2.4 g) to further enhance the gel's penetration properties.

4. pH Adjustment and Neutralization:

• Gradually add Triethanolamine (0.3 g) to the gel mixture while stirring to adjust the pH to the desired range (typically 5.5–6.0). This neutralizes the Carbomer, activating its gelling properties and thickening the formulation.

5. Preservation and Final Mixing:

• Add Methylparaben (0.15 g) to the gel as a preservative to prevent microbial growth. Mix the entire formulation thoroughly to ensure uniform consistency and stability before packaging the gel into suitable containers.

OBSERVATION:

1. Colour: The appearance of the gel should be aesthetically acceptable. The colour may vary from slightly cloudy to clear depending on the presence and concentration of ethanol in the formulation.

Procedure: Visually inspect a small amount of gel against a white background under natural or white light to observe its clarity and colour.

2. Odor: The gel should possess a mild and pleasant odor. If ethanol is used, an alcohol like Odor may be present, which is acceptable.

Procedure: Take a small quantity of the gel on a spatula and gently smell it to evaluate the presence of any characteristic or unpleasant odor.

3. Consistency: A good gel should have a uniform and semi solid consistency that is easy to apply and spread over the skin surface.

Procedure: Check the gel manually by pressing a small quantity between the fingers to assess its smoothness, uniformity, and feel.

4. PH: The pH of the gel should be compatible with the skin (between 6.5 to 7.0) to avoid irritation upon application.

Figure 1: PH Meter

Procedure:

1. Dissolve 1g of the gel in 10 ml of distilled water.

2. Measure the pH using a calibrated digital pH meter.

5. Spreadability

Theory: This test ensures how easily the gel spreads on the skin, which affects patient compliance and drug delivery.

Spread ability (gm./s) = M×L/T

Where:

M = Weight in grams

L = Length the slide moved (in cm)

T = Time in seconds

Procedure:

1. Place a small quantity of gel between two glass slides.

2.Apply a weight (usually 500g) on the top slide for 1 minute.

3. Measure the diameter of the spread gel area or note the time taken for the top slide to slip off.

 6. Drug Solubility: The active ingredient (Diclofenac Sodium) must be fully dissolved in the gel base to ensure uniform distribution and efficacy.

Procedure:

1. Visually inspect for any undissolved particles.

Optionally, analyse using UV spectrophotometry to confirm drug solubility in the formulation.

7. Viscosity: Viscosity determines the flow properties and stability of the gel. An ideal gel should have adequate viscosity for proper application and retention.

Figure 3: Brookfield Viscometer

Procedure:

1. Prepare the Sample:
   • Ensure the clindamycin gel is homogenous and at room temperature (25°C) or body temperature (37°C).
2. Setup:
   • Attach the appropriate spindle (e.g., RV Spindle 64) to the Brookfield Viscometer.
   • Place the gel in a 250 mL beaker (about 100 200 mL) and immerse the spindle, ensuring it doesn’t touch the sides or bottom.
3. Set Speed:
   • Set the viscometer to 12 RPM (or 10/50 RPM for different shear rates).
4. Measure Viscosity:
   • Allow the spindle to rotate for 30 60 seconds.
   • Record the viscosity in cP (centipoise) from the digital display.
5. Repeat (Optional):
   • Measure viscosity at different speeds (10, 20, 50 RPM) to assess shear thinning behavior.
6. Clean Up:  Clean the spindle and container thoroughly after use.

8. Simple Diffusion Test for Diclofenac Gel

MATERIALS:

1. clindamycin gel

2. Franz diffusion cell (or small glass setup)

3.Dialysis membrane or cling film

4. Warm water (37°C)

5. Phosphate buffered saline (PBS)

Figure 4: Franz Cell Diffusion Apparatus