SOP for Formulating Self-Emulsifying Drug Delivery Systems (SEDDS)

Formulating Self-Emulsifying Drug Delivery Systems (SEDDS)

1) Purpose

This SOP outlines the procedure for formulating Self-Emulsifying Drug Delivery Systems (SEDDS), which are lipid-based formulations designed to improve the bioavailability of poorly water-soluble drugs. SEDDS formulations spontaneously emulsify into fine oil-in-water emulsions when exposed to gastrointestinal fluids, enhancing drug solubilization and absorption.

2) Scope

This SOP applies to personnel involved in the formulation of SEDDS in pharmaceutical development, focusing on improving drug solubility and oral bioavailability. The procedure includes instructions for selecting excipients, blending lipid components, and conducting quality control to ensure the emulsion’s stability and droplet size distribution.

3) Responsibilities

Formulation Scientists: Responsible for selecting appropriate oils, surfactants, and co-surfactants, preparing the SEDDS formulation, and ensuring batch documentation.
QA Team: Responsible for reviewing formulation records and ensuring that the SEDDS formulations comply with SOP and GMP standards.
QC Team: Responsible for conducting quality control tests, such as droplet size analysis and stability testing.

4) Procedure

4.1 Equipment Setup

The equipment used for SEDDS formulation must be cleaned, calibrated, and ready for operation. The following equipment is necessary:

4.1.1 Required Equipment

Magnetic stirrer
Hot plate with temperature control
Homogenizer or vortex mixer
pH meter
Droplet size analyzer
Ultrasonicator (optional for droplet size reduction)

4.1.2 Calibration

4.1.2.1 Calibrate the homogenizer or vortex mixer to ensure that mixing speed is accurate as per formulation guidelines.
4.1.2.2 Calibrate the pH meter using standard buffer solutions (pH 4.0, 7.0, and 10.0).

4.2 Selection of Components

SEDDS formulations typically consist of oils, surfactants, and co-surfactants. The selection of components is critical to ensure that the system self-emulsifies and improves drug solubility. Follow these steps to select the ingredients:

4.2.1 Select oils based on the solubility of the drug. Medium-chain triglycerides (MCT) or long-chain triglycerides (LCT) are commonly used as the lipid phase.
4.2.2 Choose surfactants with an appropriate hydrophilic-lipophilic balance (HLB), typically between 12 and 18, to promote the emulsification of the lipid phase in aqueous environments.
4.2.3 Select co-surfactants, such as ethanol or propylene glycol, to enhance the fluidity of the system and facilitate the self-emulsification process.

4.3 Formulation Process

4.3.1 Preparation of the Lipid Phase

4.3.1.1 Weigh the required amount of oil (e.g., MCT or LCT) according to the formulation protocol. Record the weight in the Batch Manufacturing Record (BMR).
4.3.1.2 Heat the oil phase to 40°C-60°C on a hot plate with a temperature controller.

4.3.2 Preparation of the Surfactant and Co-Surfactant

4.3.2.1 Weigh the surfactant and co-surfactant in the ratios specified by the formulation protocol. Record the weights in the BMR.
4.3.2.2 Heat the surfactant and co-surfactant mixture to 40°C-60°C, if necessary, to facilitate dissolution.

4.3.3 Mixing the Components

4.3.3.1 Gradually add the surfactant and co-surfactant mixture to the heated oil phase while stirring continuously with a magnetic stirrer.
4.3.3.2 Continue stirring until a homogeneous mixture is formed. The mixture should appear clear and uniform.
4.3.3.3 If the formulation requires finer droplets, use a homogenizer or ultrasonicator to further reduce droplet size.

4.4 Quality Control Testing

After preparing the SEDDS, it must undergo quality control tests to confirm that the formulation meets the required specifications for droplet size, stability, and self-emulsifying properties.

4.4.1 Measure the droplet size using a droplet size analyzer. The average droplet size should typically range between 50 and 200 nm.
4.4.2 Evaluate the self-emulsification properties by adding the formulation to simulated gastric fluid (SGF) or simulated intestinal fluid (SIF) and observing whether the mixture forms a stable emulsion.
4.4.3 Check the pH of the formulation using a calibrated pH meter. Adjust if necessary to meet the product specifications.
4.4.4 Conduct stability testing by storing the formulation at room temperature and accelerated conditions (e.g., 40°C) to assess long-term stability and droplet size retention.

4.5 Storage of SEDDS

The prepared SEDDS formulation should be stored in sterilized, airtight containers. Label the containers with the batch number, formulation date, and storage conditions. Store the formulation at room temperature, and periodically assess for stability and droplet size consistency.

5) Abbreviations, if any

SEDDS: Self-Emulsifying Drug Delivery System
HLB: Hydrophilic-Lipophilic Balance
SGF: Simulated Gastric Fluid
SIF: Simulated Intestinal Fluid
QA: Quality Assurance
QC: Quality Control

6) Documents, if any

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

7) References, if any

ICH Q8: Pharmaceutical Development
FDA Guidance for Lipid-Based Drug Delivery Systems

8) SOP Version

Version 1.0

Annexure

Annexure 1: Batch Manufacturing Record Template


  
    Batch No.
    Oil Phase
    Surfactant
    Co-Surfactant
    Mixing Time
    Operator Initials
    QA Signature
  
  
    Batch Number
    Oil Type/Weight
    Surfactant Name/Weight
    Co-Surfactant Name/Weight
    Minutes
    Operator Name
    QA Name

Batch No.	Oil Phase	Surfactant	Co-Surfactant	Mixing Time	Operator Initials	QA Signature
Batch Number	Oil Type/Weight	Surfactant Name/Weight	Co-Surfactant Name/Weight	Minutes	Operator Name	QA Name