Accelerated Stability Testing of Liposome Formulations

1) Purpose

The purpose of this SOP is to outline the procedure for conducting accelerated stability testing on liposome formulations. This type of testing simulates long-term storage conditions by exposing the formulation to elevated temperatures and humidity levels over a short period. The goal is to predict the shelf life and stability of the liposomal product by observing physical and chemical changes under stress conditions.

2) Scope

This SOP applies to personnel involved in stability testing of liposomal formulations in pharmaceutical development. It covers the preparation, storage, and evaluation of liposome samples under accelerated conditions to assess their stability and predict long-term behavior.

3) Responsibilities

• Formulation Scientists: Responsible for preparing liposome batches for accelerated stability testing and ensuring sample uniformity.
• QC Team: Responsible for conducting physical and chemical stability tests at predefined intervals and documenting the results.
• QA Team: Responsible for reviewing the test results and ensuring compliance with regulatory standards.

4) Procedure

4.1 Preparation for Accelerated Testing

• 4.1.1 Prepare liposome formulations as per the manufacturing protocol. Ensure that the samples are uniform and representative of the production batch.
• 4.1.2 Label the samples with batch number, preparation date, and storage conditions.
• 4.1.3 Divide the samples into groups for different storage conditions, such as 40°C/75% RH (relative humidity) for accelerated testing and 25°C/60% RH for comparative testing.

4.2 Parameters for Stability Testing

The following parameters should be monitored during the stability study to assess both physical and chemical stability:

• 4.2.1 Particle Size Distribution: Measure the particle size distribution using dynamic light scattering (DLS) at each time point. Any significant increase in size may indicate aggregation or instability.
• 4.2.2 Zeta Potential: Measure the zeta potential to assess the colloidal stability of the liposomes.
• 4.2.3 Encapsulation Efficiency: Analyze the encapsulation efficiency of the API using high-performance liquid chromatography (HPLC) or another suitable method.
• 4.2.4 Visual Inspection: Conduct a visual inspection for signs of aggregation, precipitation, or phase separation in the samples.
• 4.2.5 pH: Measure the pH of the liposome suspension at each interval. Significant pH changes may affect stability or API release.

4.3 Sampling and Testing Time Points

• 4.3.1 Initial Test: Conduct the initial tests immediately after preparing the liposomes to establish a baseline for stability parameters.
• 4.3.2 Interim Tests: Perform stability tests at specified intervals (e.g., 1 month, 3 months, 6 months) for samples stored at 40°C/75% RH.
• 4.3.3 Final Test: Conduct the final stability tests at the end of the study period (e.g., 6 months) to determine overall stability under accelerated conditions.

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 Compare the results with baseline values to identify trends such as particle size increase, zeta potential reduction, or a decrease in encapsulation efficiency.
• 4.4.3 Analyze the data to estimate the shelf life and determine whether the formulation remains stable under accelerated conditions.

4.5 Criteria for Stability

The liposomal formulation is considered stable under accelerated conditions if it meets the following criteria throughout the study:

• 4.5.1 Particle size distribution remains within the acceptable range with no significant increase or aggregation.
• 4.5.2 Zeta potential remains within the range indicating good colloidal stability (typically ±30 mV or higher).
• 4.5.3 Encapsulation efficiency remains above the predefined threshold for the active ingredient.
• 4.5.4 No visible signs of aggregation, precipitation, or phase separation.

5) Abbreviations, if any

• DLS: Dynamic Light Scattering
• HPLC: High-Performance Liquid Chromatography
• 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
• Encapsulation Efficiency 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