Standard Operating Procedure for Mixing and Blending of Nasal Formulation Ingredients
1) Purpose
The purpose of this SOP is to outline the correct procedure for mixing and blending various ingredients used in nasal formulations, ensuring uniformity, consistency, and homogeneity in the final product. This ensures the nasal formulation meets both therapeutic efficacy and safety standards.
2) Scope
This SOP applies to all personnel involved in the formulation, preparation, and quality control of nasal sprays, powders, and gels at [Company Name]. It covers the mixing of active pharmaceutical ingredients (APIs), excipients, and other additives used in nasal formulations.
3) Responsibilities
- Operators: Responsible for carrying out the mixing and blending steps following the outlined procedure and ensuring all materials are processed as per batch records.
- Quality Assurance (QA): Ensures that the final blend is homogeneous and meets the product specifications. QA also verifies compliance with regulatory requirements.
- Maintenance Team: Responsible for the maintenance and calibration of all mixing and blending equipment to prevent contamination and ensure equipment accuracy.
4) Procedure
4.1 Preparation for Mixing and Blending
4.1.1 Material Check
- Ensure all required ingredients are available and documented in the batch manufacturing record (BMR), including APIs, excipients, and any additional ingredients.
- Verify that the quantities are weighed correctly based on formulation requirements. Record weights in the batch manufacturing record (BMR).
4.1.2 Equipment Preparation
- Inspect the blender or mixer to ensure it is clean, calibrated, and free from any contaminants from previous formulations. Record the cleaning process in the equipment logbook.
- Ensure all mixing tools and accessories, such as paddles and mixers, are assembled correctly and securely attached to the machine.
- Calibrate the mixer/blender and record the calibration details in the calibration log.
4.2 Mixing Procedure
4.2.1 Dry Powder Formulations
- For dry powder nasal formulations, transfer the weighed APIs and excipients into the powder blender. Use a conical mixer or ribbon blender for uniform distribution.
- Set the blending speed and duration as per the batch manufacturing record (BMR), typically blending for 10-15 minutes at low speed to prevent powder segregation.
- Conduct in-process testing to confirm homogeneity by taking samples from different sections of the blend. Test samples using HPLC or UV spectrophotometry.
4.2.2 Liquid Nasal Sprays
- For liquid formulations, add the required amount of excipients and diluents to the mixing vessel. Gradually introduce the APIs while stirring continuously to ensure complete dissolution.
- Use a mechanical stirrer to maintain a consistent speed and avoid vortex formation. Adjust the mixing speed according to the viscosity of the solution.
- Mix the solution until uniformity is achieved, typically between 30-60 minutes. Perform periodic checks to ensure the API is evenly distributed and the solution is homogenous.
4.2.3 Nasal Gels
- For gel formulations, add the gel-forming agents (e.g., carbomers, HPMC) to water while stirring continuously until fully hydrated. Adjust the pH to initiate gelling as required by the formulation.
- Once the base gel is prepared, introduce the API and other additives. Continue mixing until the final formulation is smooth, consistent, and free from clumps.
4.3 Blending and Homogeneity Testing
4.3.1 Homogeneity Testing for Powders
- Once the mixing is complete, take samples from three different sections of the blender (top, middle, and bottom) and test for homogeneity using validated methods (e.g., HPLC).
- The standard deviation of the test results should not exceed 2% to ensure uniform distribution of the active ingredient throughout the batch.
4.3.2 Homogeneity Testing for Liquid and Gel Formulations
- For liquid and gel formulations, take samples from different points in the mixing vessel. Perform analytical testing to confirm that the API concentration is consistent across all samples.
4.4 Documentation
- Document all steps of the blending process in the batch manufacturing record (BMR), including the duration and speed of mixing, the results of homogeneity testing, and any adjustments made during the process.
- Ensure QA personnel sign off on the batch records after verifying that the blend meets the required specifications.
4.5 Equipment Cleaning and Maintenance
- Once the mixing and blending process is complete, clean all equipment according to the cleaning validation protocol to prevent cross-contamination. Record the cleaning details in the equipment log.
- Perform routine maintenance checks on all mixing and blending equipment. Schedule regular calibration checks, and record all maintenance activities in the equipment maintenance log.
5) Abbreviations, if any
- API: Active Pharmaceutical Ingredient
- HPLC: High-Performance Liquid Chromatography
- QA: Quality Assurance
- BMR: Batch Manufacturing Record
- HPMC: Hydroxypropyl Methylcellulose
6) Documents, if any
- Batch Manufacturing Record (BMR)
- Homogeneity Testing Log
- Equipment Cleaning Log
- Calibration Log
- Maintenance Log
7) References, if any
- ICH Q8(R2) – Pharmaceutical Development Guidelines
- FDA Guidance for Industry – Nasal Spray and Inhalation Product Development
8) SOP Version
Version 1.0
Annexure
1. 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 |
2. Equipment Cleaning Log Template
| Date | Equipment ID | Cleaning Procedure | Operator Initials | QA Approval |
|---|---|---|---|---|
| DD/MM/YYYY | Equipment Name/ID | Cleaning Method | Operator Name</ td> | 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. Maintenance Log Template
| Date | Equipment ID | Maintenance Procedure | Operator Initials | QA Approval | |
|---|---|---|---|---|---|
| DD/MM/YYYY | Equipment Name/ID | Maintenance Method | Operator Name | QA Name | |