SOP for Optimizing Particle Size Distribution for Nasal Sprays

Standard Operating Procedure for Optimizing Particle Size Distribution for Nasal Sprays

1) Purpose

The purpose of this SOP is to outline the procedures for optimizing particle size distribution in nasal sprays. Proper particle size distribution is critical for effective nasal drug delivery, ensuring proper deposition in the nasal cavity and enhancing therapeutic effects.

2) Scope

This SOP applies to all personnel involved in the formulation, testing, and packaging of nasal sprays at [Company Name]. It provides detailed guidelines to ensure that the particle size distribution is consistent with the requirements for nasal drug delivery.

3) Responsibilities

Operators: Responsible for formulating and optimizing the particle size distribution in nasal sprays.
Quality Assurance (QA): Ensures that the particle size distribution meets the specifications for nasal delivery, including quality control testing and approval of the final product.
Maintenance Team: Responsible for maintaining and calibrating equipment used for particle size analysis and formulation processes.

4) Procedure

4.1 Selection of Ingredients

4.1.1 Active Ingredient Selection

Select active pharmaceutical ingredients (APIs) suitable for nasal delivery. Consider factors such as solubility, stability, and the need for

controlled particle size distribution to enhance nasal absorption.

Select excipients, such as surfactants or stabilizers, that can help achieve and maintain a consistent particle size distribution in the formulation.

4.1.2 Weighing and Preparation of Ingredients

Weigh the API and excipients using a calibrated balance. Ensure that all ingredients are weighed to within ±2% of the target weight, and record the values in the Batch Manufacturing Record (BMR).
Prepare the aqueous phase by dissolving the excipients in Water for Injection (WFI). Record all steps in the BMR.

4.2 Optimization of Particle Size

4.2.1 Homogenization

Homogenize the mixture to reduce the particle size of the suspended API. Use a high-shear homogenizer to ensure the particles are evenly distributed and within the target size range (typically 1-10 microns for nasal sprays).
Control the homogenization speed and time to achieve the desired particle size distribution. Record the homogenization parameters in the BMR, including speed, time, and temperature.

4.2.2 Micronization (if necessary)

If the desired particle size is not achieved through homogenization, micronize the API using a jet mill or ball mill to reduce the particle size to the target range.
Test the particle size after micronization using a laser diffraction particle size analyzer. Ensure that the particle size falls within the target range, typically 1-10 microns for nasal spray delivery.
Record the micronization parameters, including equipment settings and results, in the BMR.

4.2.3 Spray Drying (optional)

If the formulation requires further particle size control, use a spray dryer to achieve uniform particle size distribution. Adjust the feed rate, inlet temperature, and nozzle settings to optimize particle size.
Test the particle size distribution of the dried powder and record the results in the particle size testing log.

4.3 Particle Size Testing and Analysis

4.3.1 Laser Diffraction Testing

Use a laser diffraction particle size analyzer to measure the particle size distribution of the nasal spray formulation. Ensure that the test results are within the specified range for nasal delivery (typically 1-10 microns).
Perform the test on samples taken at different points in the production process (e.g., post-homogenization, post-micronization). Record the test results in the particle size testing log.

4.3.2 Aerosol Performance Testing

Test the aerosol performance of the nasal spray using a cascade impactor or other suitable method to assess particle deposition in the nasal cavity. Ensure the emitted dose and fine particle fraction are within the acceptable range.
Record the aerosol performance test results in the aerosol testing log.

4.4 Filtration and Filling

4.4.1 Filtration of the Formulation

Filter the formulation through a 0.22-micron filter to remove any particulates or microbial contaminants before filling.
Ensure the filter integrity is tested and record the results in the BMR.

4.4.2 Filling the Nasal Spray Containers

Transfer the sterile formulation into a calibrated filling machine. Ensure that the machine is set to dispense the correct volume (e.g., 100 µL per spray) and maintain fill accuracy within ±5% of the target volume.
Record the filling process, including the fill weight and accuracy results, in the BMR.

4.5 Quality Control Testing

4.5.1 Particle Size Distribution Testing

Conduct final particle size distribution testing on the finished product using a laser diffraction analyzer. Ensure that the particle size remains within the acceptable range for nasal spray delivery.
Document the particle size distribution results in the particle size testing log.

4.5.2 Microbial Testing

Perform microbial testing, including sterility and endotoxin tests, on the final product to ensure it is free from microbial contamination.
Record the microbial test results in the microbial testing log.

4.6 Documentation

Document all steps of the formulation process, including ingredient weighing, homogenization, micronization, spray drying, and filling, in the BMR.
Ensure that QA personnel review and approve all documentation before the product is released for distribution.

4.7 Equipment Cleaning and Calibration

Calibrate all equipment, including homogenizers, micronizers, and particle size analyzers, according to the calibration schedule. Record the calibration data in the calibration log.
Clean all equipment after each batch according to the cleaning validation protocol. Document the cleaning process in the cleaning log.

5) Abbreviations, if any

API: Active Pharmaceutical Ingredient
QA: Quality Assurance
BMR: Batch Manufacturing Record
WFI: Water for Injection

6) Documents, if any

Batch Manufacturing Record (BMR)
Particle Size Testing Log
Aerosol Testing Log
Microbial Testing Log
Calibration Log
Cleaning Log

7) References, if any

ICH Q6A – Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products
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. Aerosol Testing Log Template


  
    Date
    Formulation
    Test Results
    Test Method
    Operator Initials
    QA Approval
  
  
    DD/MM/YYYY
    Formulation Name
    Results
    Method
    Operator Name
    QA Name

Date	Formulation	Test Results	Test Method	Operator Initials	QA Approval
DD/MM/YYYY	Formulation Name	Results	Method	Operator Name	QA Name

3. Microbial Testing Log Template


  
    Date
    Formulation
    Microbial Test
    Results
    Operator Initials
    QA Approval
  
  
    DD/MM/YYYY
    Formulation Name
    Test
    Results
    Operator Name
    QA Name

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

5. Cleaning Log Template


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