SOP for Hot Melt Extrusion Process for Nasal Powders

Standard Operating Procedure for Hot Melt Extrusion Process for Nasal Powders

1) Purpose

The purpose of this SOP is to outline the procedures for using the 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
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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

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

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

Date	Equipment ID	Cleaning Procedure	Operator Initials	QA Approval
DD/MM/YYYY	Equipment Name/ID	Cleaning Method	Operator Name	QA Name

Date	Equipment ID	Calibration Procedure	Calibration Results	Operator Initials	QA Approval
DD/MM/YYYY	Equipment Name/ID	Procedure	Pass/Fail	Operator Name	QA Name