SOP for Development of Powdered Nasal Formulations

Standard Operating Procedure for Development of Powdered Nasal Formulations

1) Purpose

The purpose of this SOP is to outline the procedures for the development of powdered nasal formulations, including the selection of active pharmaceutical ingredients (APIs), excipients, and quality control measures. This method is used for dry powder nasal sprays, which are an alternative to liquid-based formulations.

2) Scope

This SOP applies to all personnel involved in the formulation, testing, and quality control of powdered nasal formulations at [Company Name]. It covers ingredient selection, formulation, blending, and testing procedures.

3) Responsibilities

Operators: Responsible for weighing, blending, and testing powdered nasal formulations as per the batch manufacturing record (BMR).
Quality Assurance (QA): Ensures that the formulation meets regulatory and quality standards, including homogeneity and particle size distribution.
Maintenance Team: Ensures that all equipment used in the formulation process is cleaned and calibrated regularly.

4) Procedure

4.1 Selection of Ingredients

4.1.1 Selection of Active Ingredients

Select APIs that are stable in a dry powder form and suitable for nasal delivery. Record the chosen API in the BMR, ensuring the concentration is appropriate for

the intended therapeutic use.

Choose excipients that are safe for nasal administration and will enhance the powder flowability and stability. Common excipients include lactose, mannitol, and starch.

4.1.2 Weighing of Ingredients

Weigh the API and excipients using a calibrated balance. Record the weights in the BMR, ensuring that all ingredients are within ±2% of the target weight.

4.2 Blending and Mixing

4.2.1 Mixing Process

Add the API and excipients into a clean and sterile blending vessel. Use a low-shear mixer to blend the powders for a specified time (e.g., 15 minutes) to ensure homogeneity. Document the mixing parameters in the BMR.
Periodically sample the powder blend to test for homogeneity. Use validated analytical methods (e.g., HPLC or UV spectrophotometry) to measure the concentration of the API in each sample.

4.2.2 Testing for Homogeneity

Test the homogeneity of the powder blend by taking samples from different points in the blending vessel (top, middle, bottom). Ensure the API concentration is uniform across samples with a deviation of no more than 2%.
Document the test results in the homogeneity testing log.

4.3 Filling and Packaging

4.3.1 Filling Process

Transfer the blended powder into a filling machine. Set the machine to dispense the required amount of powder into the nasal spray devices (e.g., 10 mg per dose). Ensure that the device is compatible with the powder formulation.
Test the fill accuracy by weighing 10 randomly selected filled devices. The variation should not exceed ±5% of the target dose. Record the results in the BMR.

4.3.2 Packaging

Seal the filled devices and ensure the packaging protects the powder from moisture and environmental degradation. Label the devices with batch numbers, expiration dates, and storage instructions.
Package the filled nasal spray devices in secondary packaging to protect them during shipping and storage. Record the packaging details in the BMR.

4.4 Quality Control Testing

4.4.1 Particle Size Testing

Test the particle size distribution of the powder formulation using a laser diffraction particle size analyzer or dynamic light scattering. Ensure the particle size falls within the range of 1-10 microns for optimal nasal delivery.
Document the particle size distribution in the particle size testing log and ensure the results meet product specifications.

4.4.2 Stability Testing

Conduct long-term stability testing on the powder formulation. Store samples under controlled conditions (e.g., 25°C, 60% RH) and test them at regular intervals (e.g., 1 month, 3 months, 6 months) for changes in API concentration, moisture content, and particle size.
Document all stability test results in the stability testing log and adjust the product expiration date if necessary.

4.5 Documentation

Document all steps of the formulation process in the BMR, including the weighing, blending, filling, and packaging procedures.
Ensure all quality control test results, including homogeneity, particle size, and stability, are recorded in the appropriate logs. QA personnel must review and sign off on the documentation before product release.

4.6 Equipment Cleaning and Calibration

Clean and sterilize all equipment used in the formulation process, including blending and filling machines, according to the cleaning validation protocol.
Calibrate all equipment as per the calibration schedule and record the results in the cleaning and calibration logs.

5) Abbreviations, if any

API: Active Pharmaceutical Ingredient
QA: Quality Assurance
BMR: Batch Manufacturing Record

6) Documents, if any

Batch Manufacturing Record (BMR)
Homogeneity Testing Log
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. 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

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. 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

3. 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

4. Cleaning Log Template


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

5. 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