Standard Operating Procedure for Use of Polymers in Nasal Formulations
1) Purpose
This SOP outlines the procedures for incorporating polymers in nasal formulations to enhance drug stability, modify release profiles, and increase the retention time of the drug in the nasal cavity. Polymers can be used to form gels, suspensions, or solutions, depending on the formulation requirements.
2) Scope
This SOP applies to all personnel involved in the formulation, preparation, and testing of nasal products containing polymers at [Company Name]. It includes procedures for polymer selection, dissolution, and quality control testing of polymer-based nasal formulations.
3) Responsibilities
- Operators: Responsible for accurately weighing and incorporating polymers into nasal formulations.
- Quality Assurance (QA): Ensures the polymer is uniformly distributed in the formulation and that the product meets quality control standards.
- Maintenance Team: Responsible for cleaning and calibrating all equipment used in the polymer incorporation process.
4) Procedure
4.1 Preparation of Materials
4.1.1 Selection of Polymer
- Select the appropriate polymer based on the desired release profile and viscosity. Common polymers used in nasal formulations include hydroxypropyl methylcellulose (HPMC), carbomers, and chitosan.
- Document the selection of the polymer in the batch manufacturing record (BMR), ensuring the polymer is pharmaceutically acceptable and safe for nasal administration.
4.1.2 Weighing and Dissolution of Polymer
- Weigh the required amount of polymer using a calibrated balance. Record the weights in the BMR, ensuring accuracy within ±2% of the target weight.
- Slowly add the polymer to water or the appropriate solvent while stirring continuously to ensure even dispersion. Heat may be applied to aid dissolution, but avoid excessive temperatures that may degrade the polymer.
- Continue stirring until the polymer is fully dissolved and the solution is clear and homogeneous. Record the stirring speed, time, and temperature in the BMR.
4.2 Incorporation of Polymer into Formulation
4.2.1 Addition of Active Ingredient
- Once the polymer solution is prepared, add the active pharmaceutical ingredient (API) to the polymer matrix. Stir the mixture continuously to ensure uniform distribution of the API within the polymer solution.
- If necessary, use a homogenizer to ensure the API is evenly distributed in the polymer solution. Record the homogenization parameters (e.g., speed, time) in the BMR.
4.2.2 Viscosity Testing
- Test the viscosity of the polymer solution using a viscometer. Record the viscosity value in the viscosity testing log, ensuring it falls within the specified range for the nasal formulation.
4.3 Filling and Packaging
4.3.1 Filling Process
- Transfer the polymer-based formulation into the filling machine. Set the machine to fill the required volume per dose (e.g., 50 µL per spray).
- Test the fill accuracy by weighing 10 randomly selected filled containers. The variation should not exceed ±5% of the target volume. Document the fill weights in the BMR.
4.3.2 Packaging
- Seal the filled containers with sterile nozzles or caps. Ensure that all containers are free from leaks and defects before packaging.
- Label the containers with the batch number, expiration date, and storage instructions. Package the containers in protective secondary packaging.
4.4 Quality Control Testing
4.4.1 Viscosity and Homogeneity Testing
- Test the viscosity of the formulation to ensure it falls within the desired range. Record the results in the viscosity testing log.
- Test the homogeneity of the formulation by sampling from different areas of the mixing vessel. Measure the concentration of the active ingredient using HPLC or another validated method. Record the results in the homogeneity testing log.
4.4.2 Stability Testing
- Conduct long-term and accelerated stability testing of the polymer-based formulation. Store samples under controlled environmental conditions (e.g., 25°C, 60% RH) and test at regular intervals.
- Document the stability test results in the stability testing log and adjust the expiration date based on the findings.
4.5 Documentation
- Document all steps of the formulation process in the BMR, including ingredient weighing, mixing, and filling processes.
- Ensure QA personnel review and sign off on all documentation before the product is released for distribution.
4.6 Equipment Cleaning and Calibration
- Clean and sterilize all equipment used in the formulation of the polymer-based nasal spray, including mixers and filling machines. Follow the cleaning validation protocol.
- Calibrate the equipment as per the calibration schedule and document the results in the cleaning and calibration logs.
5) Abbreviations, if any
- API: Active Pharmaceutical Ingredient
- QA: Quality Assurance
- BMR: Batch Manufacturing Record
6) Documents, if any
- Batch Manufacturing Record (BMR)
- Viscosity 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. Viscosity Testing Log Template
| Date | Formulation | Viscosity (cP) | Test Method | Operator Initials | QA Approval |
|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | Viscosity | 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 |