Standard Operating Procedure for Manufacturing Nasal Powders Using Dry Powder Inhalers (DPIs)
1) Purpose
This SOP outlines the procedures for manufacturing nasal powder formulations using Dry Powder Inhalers (DPIs). These formulations ensure that powders are accurately dosed, have a consistent particle size, and are effectively delivered to the nasal cavity for therapeutic use.
2) Scope
This SOP applies to all personnel involved in the manufacturing, testing, and quality control of nasal powders utilizing DPIs at [Company Name]. The document provides guidance for powder preparation, particle size control, blending, and device filling.
3) Responsibilities
- Operators: Responsible for preparing the powder formulation, blending ingredients, and ensuring proper particle size for nasal delivery.
- Quality Assurance (QA): Verifies that the product meets all specifications, including uniformity, particle size, and dosing accuracy.
- Maintenance Team: Ensures proper functioning and cleanliness of equipment, including the DPI filling machines.
4) Procedure
4.1 Equipment Setup
4.1.1 Inspection of Dry Powder Inhaler Filling Machine
- Inspect the DPI filling machine to ensure it is clean and fully operational.
- Ensure that all parts, including the powder hopper, nozzles, and dosing chambers,
are sterile and ready for use.
Record the equipment setup details in the equipment logbook.
4.1.2 Calibration of Analytical Instruments
- Calibrate all instruments used for measuring particle size and dosing uniformity. These may include laser diffraction analyzers and powder dosing machines.
- Document calibration results in the calibration log.
4.2 Material Preparation
4.2.1 Weighing and Blending
- Weigh the active pharmaceutical ingredients (APIs) and excipients (e.g., lactose, carriers) according to the batch manufacturing record (BMR).
- Mix the materials in a powder blender at the designated speed and duration, ensuring uniform distribution of the API and excipients.
- After blending, sieve the powder to ensure consistent particle size distribution, with a target size of 1-5 microns for nasal delivery.
4.2.2 Powder Homogeneity Testing
- Take samples from various points of the blend and test for uniformity using validated analytical methods (e.g., HPLC or UV spectrophotometry).
- Record the homogeneity results in the batch records.
4.3 Powder Filling in DPI Devices
4.3.1 Filling Process
- Transfer the blended powder into the DPI filling machine. Set the machine to the specified dosing quantity per inhaler (typically between 5-25 mg of powder per dose).
- Check dosing accuracy by testing 10 filled DPI units. Ensure the deviation is within ±5% of the target dose.
4.3.2 Device Assembly and Packaging
- After filling, assemble the DPI units by sealing the dosing chambers and attaching the DPI mouthpieces.
- Package the final products in sealed containers and label them with batch numbers, expiration dates, and dosage information.
4.4 Particle Size and Moisture Content Testing
4.4.1 Particle Size Analysis
- Measure the particle size distribution using
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a laser diffraction particle size analyzer. Ensure that the powder falls within the designated particle size range of 1-5 microns for nasal absorption.
4.4.2 Moisture Content Testing
- Test the moisture content of the powder using a moisture analyzer. Ensure that the moisture content is below 5% to prevent clumping and degradation of the powder.
4.5 Microbial and Endotoxin Testing
- Perform microbial testing on the final powder formulation to ensure sterility. Use standard procedures, such as plate counting or membrane filtration.
- Conduct endotoxin testing to ensure the formulation meets safety requirements.
- Document all microbial and endotoxin test results in the quality control log.
4.6 Stability Testing
- Conduct stability testing on the nasal powder to evaluate its shelf life and ensure it maintains the required potency, particle size, and moisture content over time.
- Place samples of the nasal powder in controlled environments with varying temperature and humidity conditions and test them at 1-month, 3-month, and 6-month intervals.
- Document all stability test results in the stability testing log.
5) Abbreviations, if any
- API: Active Pharmaceutical Ingredient
- DPI: Dry Powder Inhaler
- QA: Quality Assurance
- BMR: Batch Manufacturing Record
6) Documents, if any
- Batch Manufacturing Record (BMR)
- Particle Size Analysis Log
- Moisture Content Testing Log
- Microbial and Endotoxin Testing Records
- Stability Testing Log
7) References, if any
- FDA Guidance on Nasal Powder Formulations
- ICH Q8(R2) – Pharmaceutical Development Guidelines
8) SOP Version
Version 1.0
Annexure
1. Particle Size Analysis Log Template
| Date | Formulation | Particle Size (µm) | Operator Initials | QA Approval | |
|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | Size | Operator Name | QA Name | |
2. Moisture Content Testing Log Template
| Date | Formulation | Moisture Content (%) | Operator Initials | QA Approval | |
|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | Moisture | Operator Name | QA Name | |
3. Microbial and Endotoxin Testing Record Template
| Date | Formulation | Microbial Count | Endotoxin Level | Operator Initials | QA Approval |
|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | Microbial Count | Endotoxin Level | Operator Name | QA Name |
4. Stability Testing Log Template
| Date | Formulation | Storage Conditions | Test Interval | Stability Results | Operator Initials | QA Approval |
|---|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | Temperature and Humidity | 1 month, 3 months, 6 months | Pass/Fail | Operator Name | QA Name |