Evaluation of Emulsion Droplet Size Changes Over Time
1) Purpose
The purpose of this SOP is to outline the procedure for evaluating changes in emulsion droplet size over time. Monitoring droplet size distribution helps assess the stability of emulsions by identifying any signs of coalescence or instability during long-term storage.
2) Scope
This SOP applies to personnel involved in the quality control and stability testing of emulsions. It covers the preparation, sampling, and measurement of emulsion droplet size distribution using dynamic light scattering (DLS) or laser diffraction at specified intervals.
3) Responsibilities
- Formulation Scientists: Responsible for preparing emulsion samples for droplet size analysis and ensuring accurate data collection.
- QC Team: Responsible for conducting droplet size measurements and documenting the results during the stability study.
- QA Team: Responsible for reviewing the data to ensure compliance with stability protocols and regulatory standards.
4) Procedure
4.1 Sample Preparation
- 4.1.1 Prepare emulsion formulations according to the batch manufacturing protocol.
- 4.1.2 Store 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 laser diffraction device according to the manufacturer’s instructions.
- 4.2.2 Set the
appropriate parameters for droplet size measurement, including scattering angle, temperature, and refractive index.
4.3 Droplet Size Measurement
The following steps outline the procedure for measuring emulsion droplet size distribution:
- 4.3.1 Collect samples from the stored emulsions at each time point (e.g., 0 days, 1 month, 3 months, 6 months).
- 4.3.2 Dilute the sample with deionized water or a suitable solvent if necessary to achieve the required concentration for analysis.
- 4.3.3 Load the sample into the instrument and perform the droplet size measurement.
- 4.3.4 Record the mean droplet size, polydispersity index (PDI), and droplet size distribution profile.
4.4 Data Recording and Analysis
- 4.4.1 Record all test results in the Emulsion Droplet Size Distribution Report (see Annexure 1 for template).
- 4.4.2 Compare the results over time to identify any changes in droplet size, which may indicate coalescence, aggregation, or instability.
- 4.4.3 Analyze the data to assess the overall stability of the emulsion based on the droplet size distribution over time.
4.5 Acceptance Criteria
The emulsion formulation is considered stable if the following criteria are met:
- 4.5.1 Mean droplet size remains within acceptable limits, with no significant increase or coalescence.
- 4.5.2 The polydispersity index (PDI) remains below 0.3, indicating a narrow droplet size distribution and good stability.
- 4.5.3 No significant changes in droplet size distribution profile that would indicate instability.
5) Abbreviations
- DLS: Dynamic Light Scattering
- PDI: Polydispersity Index
- QC: Quality Control
- QA: Quality Assurance
6) Documents
- Emulsion Droplet 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 Emulsion-Based Drug Products
8) SOP Version
Version 1.0
Annexure
Annexure 1: Emulsion Droplet Size Distribution Report Template
| Time Point | Storage Condition | Mean Droplet Size (nm) | PDI | Droplet Size Distribution | Operator Initials |
|---|---|---|---|---|---|
| Initial | 25°C/60% RH | 100-300 nm | 0.2 | Uniform | Operator Name |
| 3 Months | 30°C/65% RH | 100-300 nm | 0.2 | Uniform | Operator Name |