SOP for Incorporating Antioxidants in Nasal Spray Formulations

Standard Operating Procedure for Incorporating Antioxidants in Nasal Spray Formulations

1) Purpose

This SOP outlines the procedure for incorporating antioxidants into nasal spray formulations to improve product stability, prevent oxidative degradation of the active pharmaceutical ingredients (APIs), and enhance shelf life.

2) Scope

This SOP applies to personnel involved in the formulation, preparation, and testing of nasal sprays that require antioxidants at [Company Name]. The antioxidants are incorporated into the formulation to prevent the oxidative degradation of APIs and excipients.

3) Responsibilities

Operators: Responsible for accurately weighing, dissolving, and incorporating antioxidants in nasal formulations.
Quality Assurance (QA): Responsible for verifying the effectiveness of antioxidants and ensuring the formulation meets all stability and regulatory guidelines.
Maintenance Team: Ensures that all mixing and blending equipment is functioning correctly and that calibration and cleaning processes are documented.

4) Procedure

4.1 Preparation and Material Check

4.1.1 Antioxidant Selection

Select appropriate antioxidants based on the formulation requirements and compatibility with the API. Common antioxidants used include ascorbic acid, sodium metabisulfite, and BHT (butylated hydroxytoluene).
Document the selected antioxidant in the batch manufacturing record (BMR), and ensure it is pharmaceutically acceptable.

4.1.2 Weighing of Antioxidants

Weigh the required amount of antioxidant according to the formulation specifications in the BMR.
Record the weights in the batch manufacturing record, ensuring accuracy within ±2% of the target weight.

4.2 Incorporation of Antioxidants

4.2.1 Solution-Based Formulations

In liquid nasal formulations, dissolve the antioxidant in the solvent phase, typically before the addition of APIs or excipients.
Ensure complete dissolution of the antioxidant by stirring at an appropriate speed for at least 10 minutes or until the solution is clear.

4.2.2 Suspension-Based Formulations

In suspension formulations, disperse the antioxidant in the bulk excipient matrix (e.g., propellant or aqueous medium) before the addition of the API.
Mix thoroughly using a mechanical stirrer to ensure uniform distribution of the antioxidant within the suspension.

4.2.3 Homogenization

If necessary, use a homogenizer to further ensure the even distribution of antioxidants in suspension formulations.
Document the speed, time, and other parameters in the BMR.

4.3 Stability Testing

4.3.1 Testing Antioxidant Effectiveness

Conduct stability tests to evaluate the effectiveness of the antioxidant in the formulation. Test samples should be exposed to controlled environmental conditions (e.g., temperature, humidity) over specified time intervals.
Perform analytical tests such as high-performance liquid chromatography (HPLC) to measure the degradation of the API with and without antioxidants.

4.3.2 Monitoring pH and Osmolality

Measure the pH and osmolality of the formulation to ensure they are within acceptable ranges for nasal sprays. Adjust if necessary by adding buffers or tonicity agents.

4.4 Documentation

Document all steps of the process in the batch manufacturing record (BMR), including antioxidant selection, weights, incorporation steps, and stability results.
Ensure QA personnel review and sign off on all documents to verify that the formulation meets stability and regulatory standards.

4.5 Equipment Cleaning and Calibration

Once the formulation process is complete, clean the equipment according to the validated cleaning procedure to prevent cross-contamination.
Document cleaning activities in the cleaning log and ensure all equipment is recalibrated according to the calibration schedule.

5) Abbreviations, if any

API: Active Pharmaceutical Ingredient
HPLC: High-Performance Liquid Chromatography
QA: Quality Assurance
BMR: Batch Manufacturing Record

6) Documents, if any

Batch Manufacturing Record (BMR)
Stability Testing Log
Cleaning Log
Calibration Log
Antioxidant Effectiveness Log

7) References, if any

FDA Guidance on Stability Testing of Nasal Sprays
ICH Q1A – Stability Testing of New Drug Substances and Products

8) SOP Version

Version 1.0

Annexure

1. Stability Testing Log Template


  
    Date
    Formulation
    Storage Conditions
    Time Interval
    Results
    Operator Initials
    QA Approval
  
  
    DD/MM/YYYY
    Formulation Name
    Temperature/Humidity
    1 month, 3 months, etc.
    Pass/Fail
    Operator Name
    QA Name

Date	Formulation	Storage Conditions	Time Interval	Results	Operator Initials	QA Approval
DD/MM/YYYY	Formulation Name	Temperature/Humidity	1 month, 3 months, etc.	Pass/Fail	Operator Name	QA Name

2. 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

3. Calibration Log Template


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

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

4. Antioxidant Effectiveness Log Template


  
    Date
    Formulation
    Antioxidant Type
    Degradation (%)
    Operator Initials
    QA Approval
  
  
    DD/MM/YYYY
    Formulation Name
    Antioxidant Name
    Degradation Percent
    Operator Name
    QA Name

Date	Formulation	Antioxidant Type	Degradation (%)	Operator Initials	QA Approval
DD/MM/YYYY	Formulation Name	Antioxidant Name	Degradation Percent	Operator Name	QA Name