Chemical Stability Testing of Liposome Formulations
1) Purpose
The purpose of this SOP is to outline the procedure for conducting chemical stability testing on liposome formulations. Chemical stability testing evaluates the integrity of the active pharmaceutical ingredient (API) and the excipients within the liposomal formulation over time, ensuring that no degradation products or other chemical changes compromise the product’s efficacy or safety.
2) Scope
This SOP applies to personnel involved in the quality control and stability testing of liposomal drug formulations. It covers the testing of the API, lipids, and other excipients to assess degradation, interactions, or loss of potency during storage under different conditions.
3) Responsibilities
- Formulation Scientists: Responsible for preparing liposome samples for chemical stability testing and ensuring sample uniformity.
- QC Team: Responsible for conducting chemical stability tests, such as HPLC, and documenting the results at predefined intervals.
- QA Team: Responsible for reviewing test results and ensuring compliance with GMP and regulatory guidelines.
4) Procedure
4.1 Preparation for Chemical Stability Testing
- 4.1.1 Prepare liposome formulations as per the manufacturing protocol, ensuring sample uniformity across all test groups.
- 4.1.2 Label samples with the batch number, preparation date, and storage conditions. Store samples under different conditions, such as 4°C, 25°C, and 40°C/75% RH for comparative analysis.
- 4.1.3 Store additional control samples at 4°C for reference during the testing process.
4.2 Parameters for Chemical Stability Testing
The following parameters should be monitored during chemical stability testing:
- 4.2.1 API Content: Measure the concentration of the active pharmaceutical ingredient using high-performance liquid chromatography (HPLC) or another suitable method at each time point. Compare the results to the initial content to detect any loss of potency.
- 4.2.2 Lipid Degradation: Analyze the lipid components of the liposome, such as phospholipids and cholesterol, for signs of oxidation or degradation using techniques like HPLC or gas chromatography (GC).
- 4.2.3 Degradation Products: Monitor for the formation of degradation products using HPLC or another appropriate method. Compare results against established specifications to ensure safety and efficacy.
- 4.2.4 pH: Measure the pH of the liposomal suspension at regular intervals. Significant pH shifts may indicate chemical degradation or instability.
4.3 Sampling and Testing Time Points
- 4.3.1 Initial Test: Conduct chemical stability tests immediately after preparing the liposomal formulation to establish baseline values.
- 4.3.2 Interim Tests: Perform chemical stability testing at specified intervals (e.g., 1 month, 3 months, 6 months) for samples stored under various conditions (e.g., 25°C/60% RH, 40°C/75% RH).
- 4.3.3 Final Test: Conduct the final chemical stability test at the end of the study period (e.g., 12 months) to determine long-term stability.
4.4 Data Recording and Analysis
- 4.4.1 Record all test results in the Chemical Stability Test Report (see Annexure 1 for the template).
- 4.4.2 Compare results from the stored samples to the baseline data to identify any trends in API degradation, lipid breakdown, or the formation of degradation products.
- 4.4.3 Analyze the data to estimate the chemical stability and shelf life of the liposomal formulation under different storage conditions.
4.5 Criteria for Chemical Stability
The liposomal formulation is considered chemically stable if it meets the following criteria throughout the study:
- 4.5.1 The concentration of the API remains within ±10% of the initial value, with no significant degradation.
- 4.5.2 Lipid components, such as phospholipids, show no significant signs of degradation (as defined by the formulation protocol).
- 4.5.3 No harmful degradation products are detected beyond acceptable limits.
- 4.5.4 pH remains within an acceptable range, with no significant shifts that would indicate instability.
5) Abbreviations, if any
- HPLC: High-Performance Liquid Chromatography
- GC: Gas Chromatography
- RH: Relative Humidity
- QC: Quality Control
- QA: Quality Assurance
6) Documents, if any
- Batch Manufacturing Record (BMR)
- Chemical Stability Test Report
- API Content Analysis Report
- Lipid Degradation Report
- pH 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: Chemical Stability Test Report Template
| Time Point | Storage Condition | API Content (%) | Lipid Integrity (%) | Degradation Products | pH | Operator Initials |
|---|---|---|---|---|---|---|
| Initial | 25°C/60% RH | 100% | 100% | None | 7.0 | Operator Name |
| 1 Month | 40°C/75% RH | 98% | 98% | None | 6.9 | Operator Name |
| 3 Months | 40°C/75% RH | 95% | 95% | Trace | 6.8 | Operator Name |