and meet regulatory standards.

Record the selection and source of essential oils in the batch manufacturing record (BMR), ensuring the oils meet the required quality standards.

4.1.2 Weighing of Essential Oils

• Weigh the essential oils using a precision balance according to the formulation specifications in the BMR.
• Record the weight of each essential oil component in the batch manufacturing record, ensuring accuracy within ±2% of the target weight.

4.1.3 Equipment Preparation

• Inspect and clean all equipment, including mixing vessels and homogenizers, to prevent cross-contamination with residual oils from previous batches.
• Record the cleaning procedure in the equipment cleaning log and ensure all equipment is calibrated and documented in the calibration log.

4.2 Incorporation of Essential Oils in Nasal Formulation

4.2.1 Solution-Based Formulations

• For liquid nasal spray formulations, add the essential oils to the aqueous phase, typically during the final mixing step. Stir continuously to ensure proper dispersion of the oils within the solution.
• Use a homogenizer if necessary to ensure even dispersion of the oils. Document the homogenization parameters (e.g., speed, time) in the batch manufacturing record.

4.2.2 Emulsion-Based Formulations

• In emulsion formulations, essential oils are incorporated into the oil phase. Mix the oil phase with the aqueous phase under high shear mixing to form a stable emulsion.
• Homogenize the formulation to ensure that the emulsion remains stable and does not separate. The droplet size should be uniform to ensure proper nasal absorption.

4.2.3 Suspension-Based Formulations

• For suspensions, essential oils should be dispersed evenly throughout the suspension medium. Stir gently to avoid foaming or separation of oil components.
• Test samples to confirm that the oils are uniformly distributed in the formulation. Document the test results in the homogeneity testing log.

4.3 Quality Control and Testing

4.3.1 Homogeneity Testing

• Test the homogeneity of the nasal spray by sampling from different areas of the mixing vessel. Use HPLC or other validated analytical techniques to measure the concentration of the essential oils across the samples.
• The results should not deviate more than 2% from the target concentration to ensure uniformity.

4.3.2 pH and Osmolality Testing

• Measure the pH of the nasal spray to ensure that it falls within the acceptable range for nasal formulations (typically 4.5-7.0).
• Test the osmolality of the formulation to ensure it is isotonic or close to isotonic with nasal secretions (around 270-330 mOsm/kg).

4.3.3 Stability Testing

• Conduct stability testing on the essential oil formulation to evaluate its shelf life. Place samples under controlled environmental conditions (temperature and humidity) and test them at 1-month, 3-month, and 6-month intervals.
• Monitor the physical and chemical properties of the nasal spray, including color, odor, pH, and oil droplet size. Document all results in the stability testing log.

4.4 Filling and Packaging

4.4.1 Filling the Nasal Spray Containers

• Transfer the finished formulation into the filling machine. Fill each nasal spray container with the required volume, ensuring consistent dosage per unit.
• Seal the containers securely and check for any leaks or imperfections in the packaging process. Record all filling and packaging parameters in the batch manufacturing record.

4.4.2 Packaging and Labeling

• Package the filled nasal spray containers in protective packaging to prevent damage. Label each unit with the batch number, expiration date, and dosage instructions.
• Ensure that all packaging materials meet regulatory standards and are free from contaminants.

4.5 Documentation

• Document all steps of the formulation and preparation process in the batch manufacturing record (BMR). This includes weighing, mixing, testing, filling, and packaging activities.
• Ensure that QA personnel review and sign off on all documentation before the batch is released for distribution.

4.6 Equipment Cleaning and Calibration

• After completing the batch, clean all equipment used in the preparation of the nasal sprays, including mixing vessels, homogenizers, and filling machines.
• Document the cleaning activities in the equipment cleaning log. Calibrate the equipment as per the calibration schedule, and document the calibration results in the calibration log.

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
• pH and Osmolality Testing Log
• Stability Testing Log
• Cleaning and Calibration Log

7) References, if any

• ICH Q1A – Stability Testing of New Drug Substances and Products
• FDA Guidance for Nasal Spray Drug Products

8) SOP Version

Version 1.0

Annexure

1. Homogeneity Testing Log Template

Date	Formulation	Test Point (Top/Middle/Bottom)	Essential Oil 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

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 and Calibration Log Template

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