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
  
  

    
 
    
 
    
 
    
 
    
 
    
 
  

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
  

    
 
    
 
    
 
    
 
    
 
    
 
  

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
  
  

    
 
    
 
    
 
    
 
    
 
    
 
  

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