Standard Operating Procedure for Incorporation of Biodegradable Polymers in Nasal Sprays
1) Purpose
This SOP describes the procedures for incorporating biodegradable polymers in nasal spray formulations to enhance drug delivery and stability. Biodegradable polymers provide controlled and sustained release properties, ensuring therapeutic efficacy.
2) Scope
This SOP applies to all personnel involved in the formulation, preparation, and quality control of nasal sprays using biodegradable polymers at [Company Name]. It covers ingredient selection, polymer dissolution, formulation, and testing procedures.
3) Responsibilities
- Operators: Responsible for accurately weighing and incorporating biodegradable polymers into nasal spray formulations.
- Quality Assurance (QA): Ensures that the formulation meets regulatory standards, including polymer dispersion and drug release profiles.
- Maintenance Team: Ensures that all equipment used in the formulation is cleaned and calibrated regularly.
4) Procedure
4.1 Selection of Biodegradable Polymers
4.1.1 Polymer Selection
- Select biodegradable polymers suitable for nasal administration and compatible with the active ingredient. Common polymers include polylactic-co-glycolic acid (PLGA) and chitosan.
- Record the selected polymer in the batch manufacturing record (BMR), ensuring that the polymer is within regulatory limits for nasal use.
4.1.2 Weighing and Dissolution
- Weigh the required amount of polymer using a calibrated balance. Ensure the weight falls within ±2% of the target weight and document the measurement in the BMR.
- Dissolve the polymer in a solvent (e.g., water, ethanol) while stirring continuously until a uniform solution is achieved. Document the dissolution process in the BMR, including the stirring speed and time.
4.2 Preparation of Nasal Spray Formulation
4.2.1 Incorporation of API
- Add the active pharmaceutical ingredient (API) to the dissolved polymer solution. Stir the mixture to ensure the API is evenly distributed within the polymer matrix.
- If necessary, use a homogenizer to ensure uniform dispersion of the API in the polymer solution. Record the homogenization parameters (e.g., speed and duration) in the BMR.
4.2.2 Testing for Homogeneity
- Test the homogeneity of the formulation by sampling from different points in the mixing vessel. Use a validated method (e.g., HPLC or UV spectrophotometry) to measure the API concentration.
- Document the homogeneity test results in the homogeneity testing log, ensuring that the API concentration variation does not exceed 2% across samples.
4.3 Filling and Packaging
4.3.1 Filling Process
- Transfer the nasal spray formulation into the filling machine. Set the machine to dispense the required dose per spray (e.g., 50 µL per spray).
- Test the fill accuracy by weighing 10 randomly selected filled units. The variation should not exceed ±5% of the target dose. Record the fill weights in the BMR.
4.3.2 Packaging
- Seal the filled containers with sterile nasal spray nozzles. Ensure that all containers are leak-free and properly labeled with batch numbers and expiration dates.
- Package the nasal spray units in secondary packaging to protect the product from environmental factors such as light and humidity.
4.4 Quality Control Testing
4.4.1 Polymer Dispersion Testing
- Test the polymer dispersion in the formulation to ensure the polymer is uniformly distributed. Use particle size analysis to measure the polymer dispersion and ensure that the particle size is within the acceptable range (e.g., 1-5 microns).
- Document the results in the polymer dispersion log and ensure that the formulation meets product specifications.
4.4.2 Drug Release Profile Testing
- Test the drug release profile of the biodegradable polymer-based nasal spray to ensure sustained release over time. Use a validated method (e.g., in vitro release testing) to measure the drug release.
- Record the drug release profile in the release profile log and ensure the release meets the product’s therapeutic specifications.
4.5 Documentation
- Document all steps of the formulation process in the BMR, including ingredient weighing, mixing, and filling procedures.
- Record all quality control test results, including polymer dispersion and drug release profiles, in the appropriate logs. QA personnel must review and sign off on the documentation before product release.
4.6 Equipment Cleaning and Calibration
- Clean and sterilize all equipment used in the formulation process, including mixers, homogenizers, and filling machines, as per the cleaning validation protocol.
- Calibrate all equipment according to the calibration schedule and document the results in the calibration log.
5) Abbreviations, if any
- API: Active Pharmaceutical Ingredient
- QA: Quality Assurance
- BMR: Batch Manufacturing Record
6) Documents, if any
- Batch Manufacturing Record (BMR)
- Polymer Dispersion Log
- Release Profile Log
- Homogeneity Testing Log
- Cleaning Log
- Calibration Log
7) References, if any
- ICH Q1A – Stability Testing Guidelines
- FDA Guidance for Nasal Drug Products
8) SOP Version
Version 1.0
Annexure
1. Polymer Dispersion Log Template
| Date | Formulation | Polymer Dispersion (%) | Test Method | Operator Initials | QA Approval |
|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | Dispersion (%) | Method | Operator Name | QA Name |
2. Release Profile Log Template
| Date | Formulation | Drug Release Profile (%) | Test Method | Operator Initials | QA Approval |
|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | Release (%) | Method | Operator Name | QA Name |
3. 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 |
4. 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 |
5. Cleaning and Calibration Log Template
| Date | Equipment ID | Cleaning/Calibration Procedure | Operator Initials | QA Approval | |
|---|---|---|---|---|---|
| DD/MM/YYYY | Equipment Name/ID | Procedure | Operator Name | QA Name | |