SOP for Preparation of Emulsions for Parenteral Use

Preparation of Emulsions for Parenteral Use

1) Purpose

The purpose of this SOP is to outline the procedure for preparing emulsions intended for parenteral administration. Parenteral emulsions are used for delivering drugs directly into the bloodstream, bypassing the digestive system, and are commonly used for intravenous, intramuscular, or subcutaneous administration. These emulsions must meet strict sterility, particle size, and stability criteria to ensure patient safety and efficacy.

2) Scope

This SOP applies to personnel involved in the formulation of emulsions for parenteral use, specifically focusing on the sterile production, droplet size optimization, and quality control testing to ensure product safety and compliance with regulatory standards.

3) Responsibilities

Formulation Scientists: Responsible for selecting appropriate components, ensuring sterile production, and maintaining proper batch documentation.
QA Team: Responsible for reviewing formulation records and ensuring that the emulsions comply with GMP and sterility standards.
QC Team: Responsible for conducting quality control tests, such as particle size analysis, sterility testing, and stability testing.

4) Procedure

4.1 Equipment Setup

Ensure that all equipment used in the preparation of emulsions for parenteral use is properly cleaned, sterilized, and calibrated. The following equipment is necessary:

4.1.1 Required Equipment

Autoclave (for sterilization)
High-shear mixer
Homogenizer
Laminar flow hood
Particle size analyzer
pH meter

4.1.2 Sterilization of Equipment

4.1.2.1 Sterilize all equipment that

will come into contact with the emulsion using an autoclave or dry heat sterilizer according to the standard operating procedures for sterilization.

4.1.2.2 Ensure the laminar flow hood is cleaned and disinfected prior to use. Perform all steps related to the emulsion preparation under aseptic conditions.

4.1.3 Equipment Calibration

4.1.3.1 Calibrate the high-shear mixer, homogenizer, and particle size analyzer according to the manufacturer’s guidelines to ensure accurate droplet size control.
4.1.3.2 Ensure the pH meter is calibrated with standard buffer solutions (pH 4.0, 7.0, and 10.0) before use.

4.2 Selection of Components

The components used in emulsions for parenteral use must meet high purity and safety standards to avoid toxicity or adverse reactions in patients. Follow these steps to select the appropriate components:

4.2.1 Select the oil phase based on the solubility of the drug and its intended route of administration (e.g., soybean oil, medium-chain triglycerides).
4.2.2 Choose emulsifiers that are approved for parenteral use, such as lecithin or egg phospholipids, with an appropriate hydrophilic-lipophilic balance (HLB) value.
4.2.3 Use sterile water for injection (WFI) as the aqueous phase. All components must be sterile and free from pyrogens.

4.3 Preparation Process

4.3.1 Preparation of the Oil and Water Phases

4.3.1.1 Weigh the required amounts of oil phase and aqueous phase components according to the formulation protocol. Record the weights in the Batch Manufacturing Record (BMR).
4.3.1.2 Dissolve the emulsifier in the water phase by heating the solution to 60°C-70°C under aseptic conditions.
4.3.1.3 Heat the oil phase to the same temperature and maintain sterility throughout the process.

4.3.2 High-Shear Mixing

4.3.2.1 Slowly add the oil phase to the water phase while mixing with a high-shear mixer. Continue mixing until a coarse emulsion is formed.
4.3.2.2 Maintain sterile conditions throughout the process, performing all steps under a laminar flow hood.

4.3.3 Homogenization

4.3.3.1 Transfer the coarse emulsion to a homogenizer for further size reduction. Adjust the pressure and cycle settings according to the formulation protocol.
4.3.3.2 Pass the emulsion through the homogenizer at high pressure (e.g., 10,000-20,000 psi) to achieve the desired droplet size.

4.4 Quality Control Testing

After the emulsion is prepared, it must undergo quality control testing to ensure it meets the required specifications for sterility, droplet size, and stability.

4.4.1 Measure the droplet size using a particle size analyzer. The droplet size should typically range between 100 nm and 500 nm for parenteral emulsions.
4.4.2 Perform sterility testing by following standard microbiological methods to confirm that the emulsion is free from contaminants.
4.4.3 Conduct pH testing using a calibrated pH meter to ensure the emulsion is within the acceptable range for parenteral use (e.g., pH 5.5-7.0).
4.4.4 Perform stability testing by storing samples at different temperatures (e.g., 4°C, 25°C, 40°C) and monitoring droplet size and emulsion stability over time.

4.5 Storage of Parenteral Emulsions

The prepared emulsion should be stored in sterilized, airtight containers, such as glass vials or ampoules. Label each container with the batch number, preparation date, and storage conditions. Store the emulsion at the recommended temperature (e.g., 2-8°C) and periodically test for stability and droplet size retention.

5) Abbreviations, if any

WFI: Water for Injection
HLB: Hydrophilic-Lipophilic Balance
QA: Quality Assurance
QC: Quality Control

6) Documents, if any

Batch Manufacturing Record (BMR)
Sterility Test Report
Droplet Size Analysis Report
Stability Test Report

7) References, if any

ICH Q7: Good Manufacturing Practice Guide
FDA Guidelines for Parenteral Emulsions

8) SOP Version

Version 1.0