SOP for Formulation of Nasal Drops

Standard Operating Procedure for Formulation of Nasal Drops

1) Purpose

This SOP outlines the procedures required for the formulation and preparation of nasal drops. The aim is to ensure accurate dosing, uniform distribution, and stability of the nasal drops for effective drug delivery.

2) Scope

This SOP applies to personnel involved in the formulation, preparation, and quality control of nasal drops at [Company Name]. It includes the steps for ingredient selection, preparation, testing, and packaging of nasal drop formulations.

3) Responsibilities

Operators: Responsible for accurately weighing, mixing, and filling nasal drop formulations as per the batch manufacturing record (BMR).
Quality Assurance (QA): Ensures that the formulation meets regulatory requirements and performs quality control testing.
Maintenance Team: Responsible for the cleaning and calibration of equipment used in the production of nasal drops.

4) Procedure

4.1 Preparation of Materials

4.1.1 Selection of Active Ingredients and Excipients

Select APIs based on their compatibility with the nasal cavity and their therapeutic action. Record the selection of APIs and excipients in the batch manufacturing record (BMR).
Choose excipients that aid in the solubility, stability, and absorption of the active ingredient (e.g., tonicity agents, preservatives, and pH adjusters).

4.1.2 Weighing of Ingredients

Weigh all ingredients accurately using a calibrated balance. Record the weights in the BMR, ensuring they fall within the specified range (±2% of target weight).
Transfer the weighed ingredients into a clean and sterile mixing vessel for further processing.

4.2 Formulation of Nasal Drops

4.2.1 Preparation of Solution

For solution-based nasal drops, dissolve the active ingredients in purified water or another approved solvent.
Ensure the solution is stirred continuously using a mechanical stirrer until all components are fully dissolved and uniformly mixed. The stirring speed and time should be documented in the BMR.

4.2.2 pH Adjustment

Measure the pH of the solution using a calibrated pH meter. Adjust the pH to the target range (typically 5.5-6.5) using a pH adjuster such as hydrochloric acid or sodium hydroxide.
Document the pH measurement and adjustment details in the pH adjustment log.

4.2.3 Filtration

Filter the final solution through a 0.22-micron filter to remove any particulates and ensure sterility. Record the filtration process in the BMR, including the type of filter used and the filtration time.

4.3 Filling and Packaging

4.3.1 Filling Process

Transfer the sterile solution into a filling machine. Set the filling machine to dispense the required dose per container (e.g., 10 mL).
Test the filling accuracy by measuring the volume of 10 randomly selected filled containers. The variation should not exceed ±5% of the target volume.

4.3.2 Packaging

Seal the filled nasal drop containers using sterile droppers or caps. Ensure that the containers are free from any leaks or defects before packaging.
Label the containers with batch numbers, expiration dates, and storage instructions. Package the containers in suitable secondary packaging to protect them from environmental conditions.

4.4 Quality Control

4.4.1 pH and Osmolality Testing

Test the pH of the nasal drop solution to ensure it is within the acceptable range for nasal administration (typically 5.5-6.5).
Test the osmolality to ensure that the solution is isotonic or near-isotonic with nasal secretions (approximately 270-330 mOsm/kg). Record all results in the pH and osmolality testing log.

4.4.2 Homogeneity Testing

Test the homogeneity of the solution by taking samples from different points in the mixing vessel. Use validated analytical methods (e.g., HPLC) to measure the concentration of the active ingredient across the samples.
Document the results in the homogeneity testing log, ensuring that the concentration does not vary by more than 2%.

4.5 Stability Testing

4.5.1 Long-Term Stability Testing

Store samples of the nasal drops under controlled environmental conditions (e.g., 25°C, 60% RH) and test them at regular intervals (e.g., 1 month, 3 months, 6 months) to assess stability.
Test for physical changes (e.g., color, odor, viscosity) and chemical stability (e.g., active ingredient concentration, pH). Record all results in the stability testing log.

4.5.2 Accelerated Stability Testing

Conduct accelerated stability testing by storing the nasal drops at higher temperatures (e.g., 40°C, 75% RH) to predict their shelf life under extreme conditions.
Document the results in the stability testing log and adjust the expiration date based on the findings.

4.6 Documentation

Document all steps of the formulation process, including ingredient weighing, pH adjustment, filtration, and filling, in the batch manufacturing record (BMR).
Ensure that all quality control tests, including pH, osmolality, homogeneity, and stability, are recorded in the appropriate logs. QA personnel must review and sign off on the documentation before product release.

4.7 Equipment Cleaning and Calibration

Clean and sterilize all equipment used in the formulation process, including mixers, filling machines, and filtration units, according to the cleaning validation protocol.
Calibrate the equipment according to the calibration schedule, and record the cleaning and calibration results in the respective logs.

5) Abbreviations, if any

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

6) Documents, if any

Batch Manufacturing Record (BMR)
pH and Osmolality 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. pH and Osmolality Testing Log Template


  
    Date
    Formulation
    pH
    Osmolality (mOsm/kg)
    Operator Initials
    QA Approval
  
  
    DD/MM/YYYY
    Formulation Name
    pH Value
    Osmolality
    Operator Name
    QA Name

Date	Formulation	pH	Osmolality (mOsm/kg)	Operator Initials	QA Approval
DD/MM/YYYY	Formulation Name	pH Value	Osmolality	Operator Name	QA Name

2. Homogeneity Testing Log Template


  
    Date
    Formulation
    Test Point (Top/Middle/Bottom)
    Active Ingredient Concentration (%)
    Operator Initials
    QA Approval
  
  
    DD/MM/YYYY
    Formulation Name
    Test Point
    Concentration
    Operator Name
    QA Name

Date	Formulation	Test Point (Top/Middle/Bottom)	Active Ingredient 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