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
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 |