Standard Operating Procedure for Formulation of Nasal Drops
1) Purpose
This SOP outlines the procedures required for the formulation and preparation of nasal drops. The aim is to ensure accurate dosing, uniform distribution, and stability of the nasal drops for effective drug delivery.
2) Scope
This SOP applies to personnel involved in the formulation, preparation, and quality control of nasal drops at [Company Name]. It includes the steps for ingredient selection, preparation, testing, and packaging of nasal drop formulations.
3) Responsibilities
- Operators: Responsible for accurately weighing, mixing, and filling nasal drop formulations as per the batch manufacturing record (BMR).
- Quality Assurance (QA): Ensures that the formulation meets regulatory requirements and performs quality control testing.
- Maintenance Team: Responsible for the cleaning and calibration of equipment used in the production of nasal drops.
4) Procedure
4.1 Preparation of Materials
4.1.1 Selection of Active Ingredients and Excipients
- Select APIs based on their compatibility with the nasal cavity and their therapeutic action. Record the selection of APIs and excipients in the batch manufacturing record (BMR).
- Choose excipients that aid in the solubility, stability, and absorption of the active ingredient (e.g., tonicity agents, preservatives, and pH adjusters).
4.1.2 Weighing of Ingredients
- Weigh all ingredients accurately using a calibrated balance. Record the weights in the BMR, ensuring they fall within the specified range (±2% of target weight).
- Transfer the weighed ingredients into a clean and sterile mixing vessel for further processing.
4.2 Formulation of Nasal Drops
4.2.1 Preparation of Solution
- For solution-based nasal drops, dissolve the active ingredients in purified water or another approved solvent.
- Ensure the solution is stirred continuously using a mechanical stirrer until all components are fully dissolved and uniformly mixed. The stirring speed and time should be documented in the BMR.
4.2.2 pH Adjustment
- Measure the pH of the solution using a calibrated pH meter. Adjust the pH to the target range (typically 5.5-6.5) using a pH adjuster such as hydrochloric acid or sodium hydroxide.
- Document the pH measurement and adjustment details in the pH adjustment log.
4.2.3 Filtration
- Filter the final solution through a 0.22-micron filter to remove any particulates and ensure sterility. Record the filtration process in the BMR, including the type of filter used and the filtration time.
4.3 Filling and Packaging
4.3.1 Filling Process
- Transfer the sterile solution into a filling machine. Set the filling machine to dispense the required dose per container (e.g., 10 mL).
- Test the filling accuracy by measuring the volume of 10 randomly selected filled containers. The variation should not exceed ±5% of the target volume.
4.3.2 Packaging
- Seal the filled nasal drop containers using sterile droppers or caps. Ensure that the containers are free from any leaks or defects before packaging.
- Label the containers with batch numbers, expiration dates, and storage instructions. Package the containers in suitable secondary packaging to protect them from environmental conditions.
4.4 Quality Control
4.4.1 pH and Osmolality Testing
- Test the pH of the nasal drop solution to ensure it is within the acceptable range for nasal administration (typically 5.5-6.5).
- Test the osmolality to ensure that the solution is isotonic or near-isotonic with nasal secretions (approximately 270-330 mOsm/kg). Record all results in the pH and osmolality testing log.
4.4.2 Homogeneity Testing
- Test the homogeneity of the solution by taking samples from different points in the mixing vessel. Use validated analytical methods (e.g., HPLC) to measure the concentration of the active ingredient across the samples.
- Document the results in the homogeneity testing log, ensuring that the concentration does not vary by more than 2%.
4.5 Stability Testing
4.5.1 Long-Term Stability Testing
- Store samples of the nasal drops under controlled environmental conditions (e.g., 25°C, 60% RH) and test them at regular intervals (e.g., 1 month, 3 months, 6 months) to assess stability.
- Test for physical changes (e.g., color, odor, viscosity) and chemical stability (e.g., active ingredient concentration, pH). Record all results in the stability testing log.
4.5.2 Accelerated Stability Testing
- Conduct accelerated stability testing by storing the nasal drops at higher temperatures (e.g., 40°C, 75% RH) to predict their shelf life under extreme conditions.
- Document the results in the stability testing log and adjust the expiration date based on the findings.
4.6 Documentation
- Document all steps of the formulation process, including ingredient weighing, pH adjustment, filtration, and filling, in the batch manufacturing record (BMR).
- Ensure that all quality control tests, including pH, osmolality, homogeneity, and stability, are recorded in the appropriate logs. QA personnel must review and sign off on the documentation before product release.
4.7 Equipment Cleaning and Calibration
- Clean and sterilize all equipment used in the formulation process, including mixers, filling machines, and filtration units, according to the cleaning validation protocol.
- Calibrate the equipment according to the calibration schedule, and record the cleaning and calibration results in the respective logs.
5) Abbreviations, if any
- API: Active Pharmaceutical Ingredient
- QA: Quality Assurance
- HPLC: High-Performance Liquid Chromatography
- BMR: Batch Manufacturing Record
6) Documents, if any
- Batch Manufacturing Record (BMR)
- pH and Osmolality 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. pH and Osmolality Testing Log Template
| Date | Formulation | pH | Osmolality (mOsm/kg) | Operator Initials | QA Approval |
|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | pH Value | Osmolality | Operator Name | QA Name |
2. Homogeneity Testing Log Template
| Date | Formulation | Test Point (Top/Middle/Bottom) | Active Ingredient 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 |