SOP for Chemical Stability Testing of Liposome Formulations

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