hot melt extrusion (HME) process to manufacture nasal powders. This process allows the formation of stable, solid dispersions of active pharmaceutical ingredients (APIs) with polymers, enhancing the drug’s bioavailability and stability.

2) Scope

This SOP applies to all personnel involved in the preparation, testing, and quality control of nasal powder formulations made using the hot melt extrusion process at [Company Name].

3) Responsibilities

• Operators: Responsible for setting up, operating, and monitoring the hot melt extrusion process and ensuring the correct parameters are followed.
• Quality Assurance (QA): Ensures that the extrusion process meets the required specifications for temperature, pressure, and homogeneity.
• Maintenance Team: Responsible for cleaning and calibrating the extrusion equipment.

4) Procedure

4.1 Preparation of Materials

4.1.1 Selection of API and Polymers

• Select the active pharmaceutical ingredients (APIs) and polymers based on their suitability for the hot melt extrusion process. The API must be thermally stable, and the polymer must be capable of forming a solid dispersion.
• Commonly used polymers for hot melt extrusion include ethylcellulose, Eudragit, and hydroxypropyl cellulose. Record the selection of API and polymer in the batch manufacturing record (BMR).

4.1.2 Weighing of Ingredients

• Weigh the required amount of API and polymer using a calibrated balance. Document the weights in the BMR, ensuring that all components are within ±2% of the target weight.

4.2 Hot Melt Extrusion Process

4.2.1 Equipment Setup

• Set up the hot melt extrusion equipment according to the manufacturer’s instructions. Ensure the extruder barrel, screw, and die are clean and ready for use. Perform a pre-operation check to verify the equipment’s functionality.
• Calibrate the temperature controls and extrusion pressure settings to ensure they are within the specified range for the formulation. Document the calibration results in the equipment calibration log.

4.2.2 Loading and Extrusion

• Load the weighed API and polymer into the extruder’s feed hopper. Set the extruder’s barrel temperature, screw speed, and pressure according to the BMR.
• As the materials pass through the heated barrel, monitor the temperature and pressure at different zones to ensure they remain within the target range. Adjust the settings as necessary to maintain consistent output.

4.2.3 Collection and Cooling

• Once the material exits the die, collect the extrudate and transfer it to a cooling tray or conveyor. Ensure that the material cools rapidly to prevent degradation or sticking.
• Record the extrusion parameters, including barrel temperature, screw speed, and pressure, in the BMR.

4.3 Milling and Sieving

4.3.1 Milling Process

• After cooling, transfer the extrudate to a milling machine to reduce the particle size of the nasal powder. Set the milling speed and time according to the BMR.
• Test the particle size distribution using a particle size analyzer and ensure it falls within the target range (typically 1-10 microns for nasal powders).

4.3.2 Sieving

• Pass the milled powder through a fine mesh sieve to ensure uniformity in particle size. Collect the sieved powder in a clean, dry container and record the yield in the BMR.

4.4 Quality Control Testing

4.4.1 Particle Size Distribution

• Test the particle size distribution of the nasal powder using a laser diffraction particle size analyzer. Ensure the particle size falls within the target range.
• Record the results in the particle size testing log.

4.4.2 Stability Testing

• Conduct stability testing of the nasal powder by storing samples at controlled environmental conditions (e.g., 25°C, 60% RH) and testing them at regular intervals (e.g., 1 month, 3 months, 6 months).
• Document all stability test results in the stability testing log.

4.5 Documentation

• Document all steps of the hot melt extrusion process, including material loading, temperature, pressure settings, and milling/sieving procedures, in the BMR.
• Ensure QA personnel review and sign off on the documentation before releasing the product.

4.6 Equipment Cleaning and Calibration

• After completing the batch, clean and sterilize the hot melt extrusion equipment and milling machines following the cleaning validation protocol.
• Calibrate the equipment as per 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)
• Particle Size Testing Log
• Stability 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. Particle Size Testing Log Template

  

    
Date
    
Formulation
    
Particle Size (µm)
    
Test Method
    
Operator Initials
    
QA Approval
  
  

    
DD/MM/YYYY
    
Formulation Name
    
Size
    
Method
    
Operator Name
    
QA Name
  
  

    
 
    
 
    
 
    
 
    
 
    
 
  

2. 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
  
  

    
 
    
 
    
 
    
 
    
 
    
 
  

3. Cleaning Log Template

  

    
Date
    
Equipment ID
    
Cleaning Procedure
    
Operator Initials
    
QA Approval
  
  

    
DD/MM/YYYY
    
Equipment Name/ID
    
Cleaning Method
    
Operator Name
    
QA Name
  
  

    
 
    
 
    
 
    
 
    
 
    
 
  

4. Calibration Log Template

  

    
Date
    
Equipment ID
    
Calibration Procedure
    
Calibration Results
    
Operator Initials
    
QA Approval
  
  

    
DD/MM/YYYY
    
Equipment Name/ID
    
Procedure
    
Pass/Fail
    
Operator Name
    
QA Name