SOP for Preparing Nasal Sprays for Systemic Drug Delivery

Standard Operating Procedure for Preparing Nasal Sprays for Systemic Drug Delivery

1) Purpose

This SOP describes the procedure for formulating and preparing nasal sprays intended for systemic drug delivery. These formulations are designed to ensure the rapid absorption of drugs through the nasal mucosa and into the bloodstream.

2) Scope

This SOP applies to personnel involved in the preparation, testing, and quality control of nasal sprays designed for systemic absorption of drugs at [Company Name]. It includes procedures for the preparation, homogeneity testing, and packaging of systemic nasal sprays.

3) Responsibilities

Operators: Responsible for accurately weighing, blending, and filling the nasal spray formulations for systemic drug delivery.
Quality Assurance (QA): Ensures that the formulation meets required systemic absorption profiles and regulatory standards.
Maintenance Team: Ensures the calibration and cleaning of all equipment involved in the preparation and filling of systemic nasal sprays.

4) Procedure

4.1 Preparation of Formulation

4.1.1 Selection of Drug and Excipients

Select drugs that are known to have high bioavailability through the nasal route. Ensure the drug is pharmaceutically acceptable and is suitable for systemic delivery.
Choose excipients that enhance absorption (e.g., surfactants, permeation enhancers) and maintain the stability of the drug. Record all components in the batch manufacturing record (BMR).

4.1.2 Weighing and Mixing

Weigh the required amounts of drug and excipients using a calibrated balance. Record the weights in the BMR.
Add the drug and excipients to the mixing vessel. Use a magnetic stirrer or mechanical mixer to ensure uniform distribution of the drug within the excipients.

4.1.3 Homogenization

If necessary, use a homogenizer to achieve a consistent particle size and uniform drug distribution. Homogenize the mixture at the recommended speed and duration as specified in the BMR.
Document the homogenization parameters, including speed and time, in the BMR.

4.2 Filling and Packaging

4.2.1 Filling Process

Transfer the homogenized formulation into the nasal spray filling machine. Set the machine to fill the appropriate volume for each spray dose (e.g., 50 µL per spray).
Test the fill accuracy by checking 10 randomly filled units. The variation should not exceed ±5% of the target dose. Record the results in the BMR.

4.2.2 Sealing and Packaging

Seal the filled nasal spray containers with sterile caps or nozzles. Ensure that the spray mechanism is functioning correctly by testing one or two units.
Package the sealed units in protective containers and label each unit with the batch number, expiration date, and storage instructions.

4.3 Quality Control

4.3.1 Homogeneity Testing

Test the homogeneity of the nasal spray formulation by sampling from different points in the mixing vessel. Use HPLC or another validated analytical technique to measure drug concentration in each sample.
Ensure the drug concentration across samples does not vary by more than 2%. Document the results in the homogeneity testing log.

4.3.2 pH and Osmolality Testing

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h of the nasal spray to ensure it falls within the acceptable range for nasal administration (typically 4.5-7.0).
Test the osmolality to ensure the formulation is isotonic or near-isotonic with nasal fluids (approximately 270-330 mOsm/kg). Document all results in the pH and osmolality testing log.

4.3.3 Absorption Testing

Perform in vitro or in vivo absorption testing to ensure the drug is rapidly absorbed through the nasal mucosa. Use validated analytical methods to measure the rate and extent of absorption.
Record the results of the absorption testing in the batch manufacturing record (BMR) and compare them to target specifications for systemic delivery.

4.4 Stability Testing

4.4.1 Long-Term Stability Testing

Conduct long-term stability testing on the formulation, storing samples at controlled temperatures (e.g., 25°C, 60% RH) and testing them at 1-month, 3-month, and 6-month intervals.
Measure the physical and chemical properties, including drug concentration, pH, and osmolality. Document all results in the stability testing log.

4.4.2 Accelerated Stability Testing

Conduct accelerated stability testing by storing samples at elevated temperatures (e.g., 40°C, 75% RH) to predict the shelf life of the formulation. Test samples at specified intervals.
Document all results in the stability testing log and adjust the product expiration date accordingly.

4.5 Documentation

Document all steps of the formulation and preparation process in the batch manufacturing record (BMR), including ingredient weights, mixing times, test results, and filling parameters.
Ensure QA personnel review and sign off on all documents before the product is released for distribution.

4.6 Equipment Cleaning and Calibration

After completing the batch, clean and sterilize all equipment, including mixers and filling machines, following the cleaning validation procedure. Document all cleaning activities in the equipment cleaning log.
Calibrate the equipment as per the calibration schedule, and record the results in the calibration log.

5) Abbreviations, if any

QA: Quality Assurance
HPLC: High-Performance Liquid Chromatography
BMR: Batch Manufacturing Record

6) Documents, if any

Batch Manufacturing Record (BMR)
Homogeneity Testing Log
pH and Osmolality Testing Log
Stability Testing Log
Absorption 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)
    Drug Concentration (%)
    Operator Initials
    QA Approval
  
  
    DD/MM/YYYY
    Formulation Name
    Test Point
    Concentration
    Operator Name
    QA Name

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

2. 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

3. Stability Testing Log Template


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

4. Absorption Testing Log Template


  
    Date
    Formulation
    Absorption Test Method
    Drug Absorption Rate
    Operator Initials
    QA Approval
  
  
    DD/MM/YYYY
    Formulation Name
    Test Method (e.g., In Vitro, In Vivo)
    Absorption Rate
    Operator Name
    QA Name

Date	Formulation	Absorption Test Method	Drug Absorption Rate	Operator Initials	QA Approval
DD/MM/YYYY	Formulation Name	Test Method (e.g., In Vitro, In Vivo)	Absorption Rate	Operator Name	QA Name

5. Cleaning and Calibration Log Template


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