4.1.2 Equipment Calibration

• 4.1.2.1 Ensure that the magnetic stirrer and high-shear mixer are calibrated for speed and time settings as per the formulation protocol.
• 4.1.2.2 Verify the calibration of the pH meter using standard buffer solutions (pH 4.0, 7.0, and 10.0).

4.2 Selection of Ingredients

The formulation of microemulsions requires the selection of oil, water, surfactants, and cosurfactants in specific ratios to achieve a stable, transparent system. Follow these steps to select the ingredients:

• 4.2.1 Choose the oil phase (e.g., medium-chain triglycerides, mineral oils) based on the solubility of the active ingredients and the intended application.
• 4.2.2 Select a surfactant and cosurfactant with the appropriate hydrophilic-lipophilic balance (HLB) values to stabilize the microemulsion. The HLB values of surfactants used for microemulsions typically range from 8-18 for oil-in-water systems and 3-6 for water-in-oil systems.
• 4.2.3 Choose the aqueous phase, usually water or a water-based solution, depending on the desired product characteristics.

4.3 Microemulsion Formation

The following steps outline the process of forming a microemulsion through careful mixing of the oil, water, surfactant, and cosurfactant phases. The microemulsion should appear clear and homogeneous:

4.3.1 Preparation of the Oil and Water Phases

• 4.3.1.1 Weigh the required amounts of oil phase and aqueous phase ingredients according to the formulation protocol. Record the weights in the Batch Manufacturing Record (BMR).
• 4.3.1.2 Dissolve the surfactant(s) and cosurfactant(s) in the appropriate phase (usually the oil phase) at the specified ratio.
• 4.3.1.3 Heat both phases to the recommended temperature (typically 40°C-60°C) using a temperature-controlled water bath.

4.3.2 Emulsion Formation

• 4.3.2.1 Slowly add the aqueous phase to the oil phase while stirring continuously with a magnetic stirrer.
• 4.3.2.2 Increase the stirring speed or switch to a high-shear mixer to ensure thorough mixing and a stable, transparent microemulsion.
• 4.3.2.3 Optionally, ultrasonicate the mixture to further reduce droplet size and achieve a finer dispersion.

4.4 Quality Control Testing of Microemulsion

After the microemulsion is prepared, it must undergo quality control testing to ensure it meets the required specifications for droplet size, transparency, and stability. Perform the following tests:

• 4.4.1 Measure the droplet size using dynamic light scattering (DLS) to confirm that the droplets are within the nanometer range (typically 10-100 nm).
• 4.4.2 Evaluate the transparency of the microemulsion by visually inspecting it for clarity. The microemulsion should appear clear and homogeneous without visible phase separation.
• 4.4.3 Check the pH of the microemulsion using a calibrated pH meter to ensure it is within the acceptable range for the product (e.g., pH 4.5-7.5).
• 4.4.4 Perform stability testing by storing samples at different temperatures (e.g., room temperature, 4°C, and 45°C) and monitoring phase separation or changes in droplet size over time.

4.5 Storage of Microemulsion

The prepared microemulsion should be stored in sterilized, airtight containers. Label each container with the batch number, preparation date, and storage conditions. Store the microemulsion at the recommended temperature (e.g., 4°C or room temperature) and periodically test for stability and droplet size over time.

5) Abbreviations, if any

• DLS: Dynamic Light Scattering
• HLB: Hydrophilic-Lipophilic Balance
• QA: Quality Assurance
• QC: Quality Control

6) Documents, if any

• Batch Manufacturing Record (BMR)
• Droplet Size Analysis Report
• Stability Test Report
• pH Calibration Log

7) References, if any

• ICH Q7: Good Manufacturing Practice Guide
• FDA Guidelines for Microemulsions in Drug Delivery Systems

8) SOP Version

Version 1.0

Annexure

Annexure 1: Batch Manufacturing Record Template

  

    
Batch No.
    
Oil Phase
    
Water Phase
    
Surfactant Type
    
Cosurfactant Type
    
Mixing Time
    
Operator Initials
    
QA Signature
  
  

    
Batch Number
    
Oil Type/Weight
    
Water Type/Volume
    
Surfactant Name
    
Cosurfactant Name
    
Minutes
    
Operator Name
    
QA Name