Determination of Liposome Size Distribution Over Time
1) Purpose
The purpose of this SOP is to outline the procedure for determining the size distribution of liposomes over time. Monitoring size distribution helps assess the stability of liposomal formulations, as any significant changes in size can indicate aggregation, degradation, or instability during storage.
2) Scope
This SOP applies to personnel involved in the quality control and stability testing of liposome formulations. It covers the preparation, sampling, and measurement of liposome size distribution using dynamic light scattering (DLS) or other suitable techniques over specified time intervals.
3) Responsibilities
- Formulation Scientists: Responsible for preparing liposome samples for size distribution analysis and ensuring that all data is accurately documented.
- QC Team: Responsible for conducting particle size analysis and documenting the results at defined intervals during stability studies.
- QA Team: Responsible for reviewing the size distribution data and ensuring compliance with regulatory standards.
4) Procedure
4.1 Sample Preparation
- 4.1.1 Prepare liposome formulations according to the batch manufacturing procedure.
- 4.1.2 Store the samples at the designated conditions (e.g., 25°C/60% RH, 30°C/65% RH) for stability testing.
- 4.1.3 Label the samples with batch number, preparation date, and storage condition.
4.2 Instrument Calibration and Setup
- 4.2.1 Calibrate the dynamic light scattering (DLS) instrument or another suitable
4.3 Particle Size Measurement
The following steps outline the procedure for measuring liposome size distribution:
- 4.3.1 Take a sample of the liposome formulation from the storage condition at each time point (e.g., 0 days, 1 month, 3 months, 6 months).
- 4.3.2 Dilute the sample with deionized water or another appropriate medium if necessary, to ensure the correct particle concentration for analysis.
- 4.3.3 Load the sample into the DLS instrument and initiate the particle size analysis.
- 4.3.4 Record the mean particle size, polydispersity index (PDI), and size distribution profile for each sample.
4.4 Data Recording and Analysis
- 4.4.1 Record the particle size distribution results in the Liposome Size Distribution Report (see Annexure 1).
- 4.4.2 Compare the results over time to assess any changes in size distribution, which may indicate aggregation, degradation, or instability.
- 4.4.3 Analyze the data to determine the stability of the liposome formulation based on the size distribution profile over time.
4.5 Acceptance Criteria
The liposomal formulation is considered stable if the following criteria are met throughout the study period:
- 4.5.1 Mean particle size remains within acceptable limits, with no significant increase or aggregation.
- 4.5.2 The polydispersity index (PDI) remains below 0.3, indicating a narrow size distribution and good uniformity.
- 4.5.3 No significant changes in the size distribution profile that would indicate instability.
5) Abbreviations
- DLS: Dynamic Light Scattering
- PDI: Polydispersity Index
- QC: Quality Control
- QA: Quality Assurance
6) Documents
- Liposome Size Distribution Report
- Batch Manufacturing Record (BMR)
- Instrument Calibration Report
7) References
- ICH Q1A: Stability Testing of New Drug Substances and Products
- FDA Guidance on Liposome Drug Products
8) SOP Version
Version 1.0
Annexure
Annexure 1: Liposome Size Distribution Report Template
| Time Point | Storage Condition | Mean Particle Size (nm) | PDI | Size Distribution | Operator Initials |
|---|---|---|---|---|---|
| Initial | 25°C/60% RH | 100-200 nm | 0.2 | Uniform | Operator Name |
| 3 Months | 30°C/65% RH | 100-200 nm | 0.2 | Uniform | Operator Name |