SOP for Use of Polymers in Nasal Formulations

Standard Operating Procedure for Use of Polymers in Nasal Formulations

1) Purpose

This SOP outlines the procedures for incorporating polymers in nasal formulations to enhance drug stability, modify release profiles, and increase the retention time of the drug in the nasal cavity. Polymers can be used to form gels, suspensions, or solutions, depending on the formulation requirements.

2) Scope

This SOP applies to all personnel involved in the formulation, preparation, and testing of nasal products containing polymers at [Company Name]. It includes procedures for polymer selection, dissolution, and quality control testing of polymer-based nasal formulations.

3) Responsibilities

Operators: Responsible for accurately weighing and incorporating polymers into nasal formulations.
Quality Assurance (QA): Ensures the polymer is uniformly distributed in the formulation and that the product meets quality control standards.
Maintenance Team: Responsible for cleaning and calibrating all equipment used in the polymer incorporation process.

4) Procedure

4.1 Preparation of Materials

4.1.1 Selection of Polymer

Select the appropriate polymer based on the desired release profile and viscosity. Common polymers used in nasal formulations include hydroxypropyl methylcellulose (HPMC), carbomers, and chitosan.
Document the selection

of the polymer in the batch manufacturing record (BMR), ensuring the polymer is pharmaceutically acceptable and safe for nasal administration.

4.1.2 Weighing and Dissolution of Polymer

Weigh the required amount of polymer using a calibrated balance. Record the weights in the BMR, ensuring accuracy within ±2% of the target weight.
Slowly add the polymer to water or the appropriate solvent while stirring continuously to ensure even dispersion. Heat may be applied to aid dissolution, but avoid excessive temperatures that may degrade the polymer.
Continue stirring until the polymer is fully dissolved and the solution is clear and homogeneous. Record the stirring speed, time, and temperature in the BMR.

4.2 Incorporation of Polymer into Formulation

4.2.1 Addition of Active Ingredient

Once the polymer solution is prepared, add the active pharmaceutical ingredient (API) to the polymer matrix. Stir the mixture continuously to ensure uniform distribution of the API within the polymer solution.
If necessary, use a homogenizer to ensure the API is evenly distributed in the polymer solution. Record the homogenization parameters (e.g., speed, time) in the BMR.

4.2.2 Viscosity Testing

Test the viscosity of the polymer solution using a viscometer. Record the viscosity value in the viscosity testing log, ensuring it falls within the specified range for the nasal formulation.

4.3 Filling and Packaging

4.3.1 Filling Process

Transfer the polymer-based formulation into the filling machine. Set the machine to fill the required volume per dose (e.g., 50 µL per spray).
Test the fill accuracy by weighing 10 randomly selected filled containers. The variation should not exceed ±5% of the target volume. Document the fill weights in the BMR.

4.3.2 Packaging

Seal the filled containers with sterile nozzles or caps. Ensure that all containers are free from leaks and defects before packaging.
Label the containers with the batch number, expiration date, and storage instructions. Package the containers in protective secondary packaging.

4.4 Quality Control Testing

4.4.1 Viscosity and Homogeneity Testing

Test the viscosity of the formulation to ensure it falls within the desired range. Record the results in the viscosity testing log.
Test the homogeneity of the formulation by sampling from different areas of the mixing vessel. Measure the concentration of the active ingredient using HPLC or another validated method. Record the results in the homogeneity testing log.

4.4.2 Stability Testing

Conduct long-term and accelerated stability testing of the polymer-based formulation. Store samples under controlled environmental conditions (e.g., 25°C, 60% RH) and test at regular intervals.
Document the stability test results in the stability testing log and adjust the expiration date based on the findings.

4.5 Documentation

Document all steps of the formulation process in the BMR, including ingredient weighing, mixing, and filling processes.
Ensure QA personnel review and sign off on all documentation before the product is released for distribution.

4.6 Equipment Cleaning and Calibration

Clean and sterilize all equipment used in the formulation of the polymer-based nasal spray, including mixers and filling machines. Follow the cleaning validation protocol.
Calibrate the equipment as per the calibration schedule and document 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)
Viscosity Testing Log
Homogeneity Testing Log
Stability Testing Log
Cleaning Log
Calibration Log

7) References, if any

ICH Q1A – Stability Testing Guidelines
FDA Guidance on Nasal Drug Products

8) SOP Version

Version 1.0

Annexure

1. Viscosity Testing Log Template


  
    Date
    Formulation
    Viscosity (cP)
    Test Method
    Operator Initials
    QA Approval
  
  
    DD/MM/YYYY
    Formulation Name
    Viscosity
    Method
    Operator Name
    QA Name

Date	Formulation	Viscosity (cP)	Test Method	Operator Initials	QA Approval
DD/MM/YYYY	Formulation Name	Viscosity	Method	Operator Name	QA Name

2. 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

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
    Calibration Method
    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	Calibration Method	Pass/Fail	Operator Name	QA Name