SOP for Conducting Physical Stability Studies on Liposomes

Conducting Physical Stability Studies on Liposomes

1) Purpose

The purpose of this SOP is to outline the procedure for conducting physical stability studies on liposomal formulations. Physical stability studies are critical to ensure that liposomes retain their structural integrity, particle size distribution, and colloidal stability over time under different storage conditions. This helps in determining the shelf life and suitability of the formulation for clinical or commercial use.

2) Scope

This SOP applies to all personnel involved in stability testing of liposomal formulations. It provides guidelines for evaluating physical stability through particle size analysis, zeta potential measurement, and visual inspection for any signs of aggregation or phase separation under both standard and accelerated storage conditions.

3) Responsibilities

Formulation Scientists: Responsible for preparing liposomal formulations for stability testing and ensuring that all relevant data are documented.
QC Team: Responsible for conducting the physical stability tests at various time intervals and conditions and documenting the results.
QA Team: Responsible for reviewing and approving the stability study results and ensuring compliance with regulatory guidelines.

4) Procedure

4.1 Preparation for Stability Testing

4.1.1 Prepare sufficient quantities of liposomal formulation for stability testing, ensuring uniformity across all test samples.
4.1.2 Store the prepared liposomes in sterilized, airtight containers and label each with the batch number, date of preparation, and storage conditions.
4.1.3 Prepare samples for different storage conditions (e.g., 4°C, 25°C, 40°C) as required by the stability study protocol.

4.2 Test Parameters for Physical Stability

The following physical parameters must be monitored at specified time intervals during the stability study:

4.2.1 Particle Size Distribution: Measure the average particle size and particle size distribution using dynamic light scattering (DLS) or another appropriate technique. Record any significant changes in size over time.
4.2.2 Zeta Potential: Measure the zeta potential of the liposomal formulation to assess colloidal stability. A higher absolute zeta potential typically indicates better stability.
4.2.3 Visual Inspection: Perform visual inspections at regular intervals to check for any signs of aggregation, phase separation, or sedimentation in the liposomal formulation.
4.2.4 pH Measurement: Measure the pH of the liposomal suspension at each time point. Record any significant fluctuations that may affect stability or API release.

4.3 Time Points for Sampling

4.3.1 Initial Test: Conduct the initial physical stability tests immediately after preparing the liposomes.
4.3.2 Interim Tests: Conduct tests at specified intervals (e.g., 1 month, 3 months, 6 months) for samples stored at different conditions.
4.3.3 Final Test: Perform the final stability tests at the end of the designated study period (e.g., 12 months).

4.4 Data Recording and Analysis

4.4.1 Record all test results in the Stability Test Report (see Annexure 1 for the template).
4.4.2 Analyze the data to identify any trends in physical stability, such as increasing particle size, decreasing zeta potential, or visible signs of aggregation.
4.4.3 Compare the data across different storage conditions to determine the optimal conditions for maintaining liposome stability.

4.5 Criteria for Stability

The liposomal formulation is considered physically stable if it meets the following criteria throughout the study period:

4.5.1 Particle size distribution remains within acceptable limits (as defined by the formulation protocol).
4.5.2 Zeta potential values remain within the range indicating colloidal stability (typically ±30 mV or higher).
4.5.3 No significant changes in pH, and no visible aggregation, phase separation, or precipitation.

5) Abbreviations, if any

DLS: Dynamic Light Scattering
QC: Quality Control
QA: Quality Assurance

6) Documents, if any

Batch Manufacturing Record (BMR)
Stability Test Report
Particle Size Analysis Report
Zeta Potential Measurement Report

7) References, if any

ICH Q1A: Stability Testing of New Drug Substances and Products
FDA Guidelines for Stability Testing of Liposomal Products

8) SOP Version

Version 1.0

Annexure

Annexure 1: Stability Test Report Template


  
    Time Point
    Storage Condition
    Particle Size (nm)
    Zeta Potential (mV)
    pH
    Visual Inspection
    Operator Initials
  
  
    Initial
    4°C
    100-200 nm
    -30 to -50 mV
    7.0
    No aggregation
    Operator Name
  
  
    1 Month
    25°C
    100-200 nm
    -30 to -50 mV
    7.0
    No aggregation
    Operator Name
  
  
    3 Months
    40°C
    100-200 nm
    -30 to -50 mV
    7.0
    No aggregation
    Operator Name