Standard Operating Procedure for pH and Osmolality Control in Nasal Formulations
1) Purpose
The purpose of this SOP is to provide a detailed process for monitoring and adjusting the pH and osmolality of nasal formulations to maintain product stability, safety, and efficacy for nasal drug delivery.
2) Scope
This SOP applies to all personnel involved in the formulation, testing, and quality control of nasal spray and suspension products at [Company Name].
3) Responsibilities
- Operators: Responsible for measuring, monitoring, and adjusting the pH and osmolality during the formulation process.
- QA: Verifies the pH and osmolality values and ensures they comply with formulation requirements and safety standards.
4) Procedure
4.1 pH Measurement and Adjustment
4.1.1 Equipment Preparation
- Ensure the pH meter is calibrated with standard buffer solutions (e.g., pH 4.0, 7.0) before testing the formulation.
- Record the calibration data in the pH logbook.
4.1.2 pH Testing
- Measure the pH of the nasal formulation by dipping the electrode into the sample.
- Record the pH value and compare it with the target range as specified in the formulation guidelines.
4.1.3 pH Adjustment
- If the pH is outside the target range, adjust it by slowly adding a dilute acid (e.g., hydrochloric acid) or base (e.g., sodium hydroxide) until the desired pH is achieved.
- After each addition, thoroughly mix the formulation and recheck the pH.
- Document any adjustments made in the batch manufacturing record (BMR).
4.2 Osmolality Measurement and Adjustment
4.2.1 Osmolality Testing
- Ensure the osmolality meter is calibrated and in working condition. Document the calibration in the equipment log.
- Take a sample of the nasal formulation and measure the osmolality using an osmolality meter.
- Compare the osmolality value with the desired range (typically between 270-330 mOsm/kg for nasal formulations).
4.2.2 Osmolality Adjustment
- If the osmolality is too high, dilute the formulation with purified water or another isotonic solution to bring it within the target range.
- If the osmolality is too low, adjust by adding small amounts of a tonicity agent (e.g., sodium chloride).
- Document all adjustments and final osmolality readings in the BMR.
4.3 Stability Testing
4.3.1 Stability Testing for pH and Osmolality
- Conduct stability tests at specific intervals (e.g., 1, 3, 6 months) to monitor changes in pH and osmolality over time.
- Record the results of stability tests in the stability testing log.
4.4 Documentation
- Record all pH and osmolality measurements, adjustments, and test results in the batch manufacturing record (BMR).
- Ensure that all documentation is reviewed and signed off by QA personnel for compliance with regulatory requirements.
5) Abbreviations, if any
- QA: Quality Assurance
- BMR: Batch Manufacturing Record
6) Documents, if any
- Batch Manufacturing Record (BMR)
- pH Logbook
- Osmolality Testing Log
7) References, if any
- ICH Q3A – Stability Testing of New Drug Substances and Products
- USP 39 – pH and Osmolality Guidelines for Nasal Products
8) SOP Version
Version 1.0
Annexure
pH and Osmolality Log Template
| Date | Formulation | pH | Osmolality (mOsm/kg) | Operator Initials | QA Approval |
|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | pH Value | Osmolality | Operator Name | QA Name |