Standard Operating Procedure for Optimizing Particle Size Distribution for Nasal Sprays
1) Purpose
The purpose of this SOP is to outline the procedures for optimizing particle size distribution in nasal sprays. Proper particle size distribution is critical for effective nasal drug delivery, ensuring proper deposition in the nasal cavity and enhancing therapeutic effects.
2) Scope
This SOP applies to all personnel involved in the formulation, testing, and packaging of nasal sprays at [Company Name]. It provides detailed guidelines to ensure that the particle size distribution is consistent with the requirements for nasal drug delivery.
3) Responsibilities
- Operators: Responsible for formulating and optimizing the particle size distribution in nasal sprays.
- Quality Assurance (QA): Ensures that the particle size distribution meets the specifications for nasal delivery, including quality control testing and approval of the final product.
- Maintenance Team: Responsible for maintaining and calibrating equipment used for particle size analysis and formulation processes.
4) Procedure
4.1 Selection of Ingredients
4.1.1 Active Ingredient Selection
- Select active pharmaceutical ingredients (APIs) suitable for nasal delivery. Consider factors such as solubility, stability, and the need for controlled particle size distribution to enhance nasal absorption.
- Select excipients, such as surfactants or stabilizers, that can help achieve and maintain a consistent particle size distribution in the formulation.
4.1.2 Weighing and Preparation of Ingredients
- Weigh the API and excipients using a calibrated balance. Ensure that all ingredients are weighed to within ±2% of the target weight, and record the values in the Batch Manufacturing Record (BMR).
- Prepare the aqueous phase by dissolving the excipients in Water for Injection (WFI). Record all steps in the BMR.
4.2 Optimization of Particle Size
4.2.1 Homogenization
- Homogenize the mixture to reduce the particle size of the suspended API. Use a high-shear homogenizer to ensure the particles are evenly distributed and within the target size range (typically 1-10 microns for nasal sprays).
- Control the homogenization speed and time to achieve the desired particle size distribution. Record the homogenization parameters in the BMR, including speed, time, and temperature.
4.2.2 Micronization (if necessary)
- If the desired particle size is not achieved through homogenization, micronize the API using a jet mill or ball mill to reduce the particle size to the target range.
- Test the particle size after micronization using a laser diffraction particle size analyzer. Ensure that the particle size falls within the target range, typically 1-10 microns for nasal spray delivery.
- Record the micronization parameters, including equipment settings and results, in the BMR.
4.2.3 Spray Drying (optional)
- If the formulation requires further particle size control, use a spray dryer to achieve uniform particle size distribution. Adjust the feed rate, inlet temperature, and nozzle settings to optimize particle size.
- Test the particle size distribution of the dried powder and record the results in the particle size testing log.
4.3 Particle Size Testing and Analysis
4.3.1 Laser Diffraction Testing
- Use a laser diffraction particle size analyzer to measure the particle size distribution of the nasal spray formulation. Ensure that the test results are within the specified range for nasal delivery (typically 1-10 microns).
- Perform the test on samples taken at different points in the production process (e.g., post-homogenization, post-micronization). Record the test results in the particle size testing log.
4.3.2 Aerosol Performance Testing
- Test the aerosol performance of the nasal spray using a cascade impactor or other suitable method to assess particle deposition in the nasal cavity. Ensure the emitted dose and fine particle fraction are within the acceptable range.
- Record the aerosol performance test results in the aerosol testing log.
4.4 Filtration and Filling
4.4.1 Filtration of the Formulation
- Filter the formulation through a 0.22-micron filter to remove any particulates or microbial contaminants before filling.
- Ensure the filter integrity is tested and record the results in the BMR.
4.4.2 Filling the Nasal Spray Containers
- Transfer the sterile formulation into a calibrated filling machine. Ensure that the machine is set to dispense the correct volume (e.g., 100 µL per spray) and maintain fill accuracy within ±5% of the target volume.
- Record the filling process, including the fill weight and accuracy results, in the BMR.
4.5 Quality Control Testing
4.5.1 Particle Size Distribution Testing
- Conduct final particle size distribution testing on the finished product using a laser diffraction analyzer. Ensure that the particle size remains within the acceptable range for nasal spray delivery.
- Document the particle size distribution results in the particle size testing log.
4.5.2 Microbial Testing
- Perform microbial testing, including sterility and endotoxin tests, on the final product to ensure it is free from microbial contamination.
- Record the microbial test results in the microbial testing log.
4.6 Documentation
- Document all steps of the formulation process, including ingredient weighing, homogenization, micronization, spray drying, and filling, in the BMR.
- Ensure that QA personnel review and approve all documentation before the product is released for distribution.
4.7 Equipment Cleaning and Calibration
- Calibrate all equipment, including homogenizers, micronizers, and particle size analyzers, according to the calibration schedule. Record the calibration data in the calibration log.
- Clean all equipment after each batch according to the cleaning validation protocol. Document the cleaning process in the cleaning log.
5) Abbreviations, if any
- API: Active Pharmaceutical Ingredient
- QA: Quality Assurance
- BMR: Batch Manufacturing Record
- WFI: Water for Injection
6) Documents, if any
- Batch Manufacturing Record (BMR)
- Particle Size Testing Log
- Aerosol Testing Log
- Microbial Testing Log
- Calibration Log
- Cleaning Log
7) References, if any
- ICH Q6A – Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products
- FDA Guidance for Nasal Drug Products
8) SOP Version
Version 1.0
Annexure
1. Particle Size Testing Log Template
| Date | Formulation | Particle Size (µm) | Test Method | Operator Initials | QA Approval |
|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | Size | Method | Operator Name | QA Name |
2. Aerosol Testing Log Template
| Date | Formulation | Test Results | Test Method | Operator Initials | QA Approval |
|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | Results | Method | Operator Name | QA Name |
3. Microbial Testing Log Template
| Date | Formulation | Microbial Test | Results | Operator Initials | QA Approval |
|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | Test | Results | Operator Name | QA Name |
4. Calibration Log Template
| Date | Equipment ID | Calibration Procedure | Calibration Results | Operator Initials | QA Approval |
|---|---|---|---|---|---|
| DD/MM/YYYY | Equipment Name/ID | Procedure | Pass/Fail | Operator Name | QA Name |
5. Cleaning Log Template
| Date | Equipment ID | Cleaning Procedure | Operator Initials | QA Approval | |
|---|---|---|---|---|---|
| DD/MM/YYYY | Equipment Name/ID | Cleaning Method | Operator Name | QA Name | |