Standard Operating Procedure for Preparation of Nasal Spray Emulsions
1) Purpose
The purpose of this SOP is to outline the procedures required for the preparation and quality control of nasal spray emulsions. These formulations consist of emulsified drug particles to ensure stability and efficient drug delivery to the nasal cavity.
2) Scope
This SOP applies to all personnel involved in the formulation, testing, and packaging of nasal spray emulsions at [Company Name]. It includes procedures for ingredient selection, emulsion preparation, quality control, and packaging.
3) Responsibilities
- Operators: Responsible for weighing, mixing, emulsifying, and filling the nasal spray emulsions as per the batch manufacturing record (BMR).
- Quality Assurance (QA): Ensures the emulsion meets the required stability, homogeneity, and particle size specifications.
- Maintenance Team: Ensures that all equipment used in the emulsion preparation is cleaned, calibrated, and maintained.
4) Procedure
4.1 Preparation of Materials
4.1.1 Selection of Oil and Aqueous Phases
- Select oils and aqueous components that are compatible with the API and suitable for nasal administration. Record the chosen components in the BMR.
- Select surfactants to stabilize the emulsion. Common surfactants include polysorbates,
lecithin, and sorbitan esters. Ensure that all components meet regulatory requirements.
4.1.2 Weighing of Ingredients
- Weigh the required quantities of the oil phase, aqueous phase, surfactants, and API using a calibrated balance. Record the weights in the BMR, ensuring the accuracy is within ±2% of the target weight.
4.2 Emulsion Preparation
4.2.1 Emulsification Process
- Heat the oil phase and aqueous phase separately to the required temperature (typically 40-50°C) as specified in the BMR. Use a temperature-controlled water bath if necessary.
- Slowly add the oil phase to the aqueous phase while continuously stirring the mixture to form an emulsion. Use a high-shear mixer to homogenize the mixture and achieve the desired droplet size.
- Continue mixing until the emulsion is uniform and stable. Record the mixing speed, time, and temperature in the BMR.
4.2.2 Homogenization
- Further homogenize the emulsion using a homogenizer or high-pressure emulsification equipment. This step reduces droplet size to ensure uniformity and stability of the emulsion.
- Test the droplet size using a particle size analyzer and record the results in the particle size testing log. The target droplet size for nasal emulsions is typically 1-5 microns.
4.3 Filling and Packaging
4.3.1 Filling Process
- Transfer the homogenized emulsion into the nasal spray filling machine. Set the machine to fill the appropriate dose (e.g., 100 µL per spray) into sterile containers.
- Test the fill accuracy by weighing 10 filled containers. The variation should not exceed ±5% of the target volume. Record the fill weights in the BMR.
4.3.2 Packaging
- Seal the containers with sterile nasal spray nozzles or caps. Ensure that all containers are free of leaks or defects before final packaging.
- Label the containers with the batch number, expiration date, and storage instructions. Package the containers in suitable secondary packaging to protect them from light and temperature fluctuations.
4.4 Quality Control Testing
4.4.1 Stability and Homogeneity Testing
- Test the stability of the emulsion by monitoring the physical appearance (e.g., phase separation, color changes) over time. Store samples under controlled conditions (e.g., 25°C, 60% RH) and test at regular intervals (e.g., 1 month, 3 months, 6 months).
- Test the homogeneity of the emulsion by taking samples from different points in the mixing vessel. Measure the concentration of the active ingredient using HPLC or UV spectrophotometry. Record the results in the homogeneity testing log.
4.4.2 Particle Size Testing
- Test the particle size distribution of the emulsion using a laser diffraction particle size analyzer or dynamic light scattering. Ensure that the droplet size falls within the specified range (1-5 microns).
- Document the results in the particle size testing log and ensure that the particle size distribution remains consistent over time.
4.5 Documentation
- Document all steps of the formulation process in the BMR, including the weighing of ingredients, emulsification parameters, and filling process.
- Record the results of quality control tests, including particle size, homogeneity, and stability testing, in the appropriate logs. QA personnel must review and sign off on the documentation before product release.
4.6 Equipment Cleaning and Calibration
- After completing the batch, clean and sterilize all equipment used in the preparation of the nasal spray emulsion, including mixers, homogenizers, and filling machines. Follow the cleaning validation protocol.
- Calibrate the equipment as per the calibration schedule. Record all cleaning and calibration activities in the respective logs.
5) Abbreviations, if any
- API: Active Pharmaceutical Ingredient
- QA: Quality Assurance
- BMR: Batch Manufacturing Record
6) Documents, if any
- Batch Manufacturing Record (BMR)
- Particle Size Testing Log
- Homogeneity Testing Log
- Stability Testing Log
- Cleaning Log
- Calibration Log
7) References, if any
- ICH Q1A – Stability Testing Guidelines
- FDA Guidance on 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. Homogeneity Testing Log Template
| Date | Formulation | Test Point (Top/Middle/Bottom) | API Concentration (%) | Operator Initials | QA Approval |
|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | Test Point | Concentration | Operator Name | QA Name |
3. Stability Testing Log Template
| Date | Formulation | Storage Conditions | Time Interval | Stability Results | Operator Initials | QA Approval |
|---|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | Temperature and Humidity | 1 month, 3 months, etc. | Pass/Fail | Operator Name | QA Name |
4. Cleaning Log Template
| Date | Equipment ID | Cleaning Procedure | Operator Initials | QA Approval | |
|---|---|---|---|---|---|
| DD/MM/YYYY | Equipment Name/ID | Cleaning Method | Operator Name | QA Name | |
5. Calibration Log Template
| Date | Equipment ID | Calibration Procedure | Calibration Results | Operator Initials | QA Approval |
|---|---|---|---|---|---|
| DD/MM/YYYY | Equipment Name/ID | Calibration Method | Pass/Fail | Operator Name | QA Name |