Standard Operating Procedure for Incorporating Antioxidants in Nasal Spray Formulations
1) Purpose
This SOP outlines the procedure for incorporating antioxidants into nasal spray formulations to improve product stability, prevent oxidative degradation of the active pharmaceutical ingredients (APIs), and enhance shelf life.
2) Scope
This SOP applies to personnel involved in the formulation, preparation, and testing of nasal sprays that require antioxidants at [Company Name]. The antioxidants are incorporated into the formulation to prevent the oxidative degradation of APIs and excipients.
3) Responsibilities
- Operators: Responsible for accurately weighing, dissolving, and incorporating antioxidants in nasal formulations.
- Quality Assurance (QA): Responsible for verifying the effectiveness of antioxidants and ensuring the formulation meets all stability and regulatory guidelines.
- Maintenance Team: Ensures that all mixing and blending equipment is functioning correctly and that calibration and cleaning processes are documented.
4) Procedure
4.1 Preparation and Material Check
4.1.1 Antioxidant Selection
- Select appropriate antioxidants based on the formulation requirements and compatibility with the API. Common antioxidants used include ascorbic acid, sodium metabisulfite, and BHT (butylated hydroxytoluene).
- Document the selected antioxidant in the batch manufacturing record (BMR), and ensure it is pharmaceutically acceptable.
4.1.2 Weighing of Antioxidants
- Weigh the required amount of antioxidant according to the formulation specifications in the BMR.
- Record the weights in the batch manufacturing record, ensuring accuracy within ±2% of the target weight.
4.2 Incorporation of Antioxidants
4.2.1 Solution-Based Formulations
- In liquid nasal formulations, dissolve the antioxidant in the solvent phase, typically before the addition of APIs or excipients.
- Ensure complete dissolution of the antioxidant by stirring at an appropriate speed for at least 10 minutes or until the solution is clear.
4.2.2 Suspension-Based Formulations
- In suspension formulations, disperse the antioxidant in the bulk excipient matrix (e.g., propellant or aqueous medium) before the addition of the API.
- Mix thoroughly using a mechanical stirrer to ensure uniform distribution of the antioxidant within the suspension.
4.2.3 Homogenization
- If necessary, use a homogenizer to further ensure the even distribution of antioxidants in suspension formulations.
- Document the speed, time, and other parameters in the BMR.
4.3 Stability Testing
4.3.1 Testing Antioxidant Effectiveness
- Conduct stability tests to evaluate the effectiveness of the antioxidant in the formulation. Test samples should be exposed to controlled environmental conditions (e.g., temperature, humidity) over specified time intervals.
- Perform analytical tests such as high-performance liquid chromatography (HPLC) to measure the degradation of the API with and without antioxidants.
4.3.2 Monitoring pH and Osmolality
- Measure the pH and osmolality of the formulation to ensure they are within acceptable ranges for nasal sprays. Adjust if necessary by adding buffers or tonicity agents.
4.4 Documentation
- Document all steps of the process in the batch manufacturing record (BMR), including antioxidant selection, weights, incorporation steps, and stability results.
- Ensure QA personnel review and sign off on all documents to verify that the formulation meets stability and regulatory standards.
4.5 Equipment Cleaning and Calibration
- Once the formulation process is complete, clean the equipment according to the validated cleaning procedure to prevent cross-contamination.
- Document cleaning activities in the cleaning log and ensure all equipment is recalibrated according to the calibration schedule.
5) Abbreviations, if any
- API: Active Pharmaceutical Ingredient
- HPLC: High-Performance Liquid Chromatography
- QA: Quality Assurance
- BMR: Batch Manufacturing Record
6) Documents, if any
- Batch Manufacturing Record (BMR)
- Stability Testing Log
- Cleaning Log
- Calibration Log
- Antioxidant Effectiveness Log
7) References, if any
- FDA Guidance on Stability Testing of Nasal Sprays
- ICH Q1A – Stability Testing of New Drug Substances and Products
8) SOP Version
Version 1.0
Annexure
1. Stability Testing Log Template
| Date | Formulation | Storage Conditions | Time Interval | Results | Operator Initials | QA Approval |
|---|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | Temperature/Humidity | 1 month, 3 months, etc. | Pass/Fail | Operator Name | QA Name |
2. Cleaning Log Template
| Date | Equipment ID | Cleaning Procedure | Operator Initials | QA Approval |
|---|---|---|---|---|
| DD/MM/YYYY | Equipment Name/ID | Cleaning Method | Operator Name | QA Name |
3. 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 |
4. Antioxidant Effectiveness Log Template
| Date | Formulation | Antioxidant Type | Degradation (%) | Operator Initials | QA Approval |
|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | Antioxidant Name | Degradation Percent | Operator Name | QA Name |