Procedure for pH Adjustment During Ointment Development
| Department | Research and Development (R&D)/Quality Control |
|---|---|
| SOP No. | FD-017 |
| Supersedes | V 1.0 |
| Page No. | Page X of Y |
| Issue Date | [Insert Issue Date] |
| Effective Date | [Insert Effective Date] |
| Review Date | [Insert Review Date] |
1. Purpose
The purpose of this Standard Operating Procedure (SOP) is to define a systematic approach for adjusting and controlling the pH of ointments during formulation development. Proper pH balance ensures product stability, efficacy, and skin compatibility.
2. Scope
This SOP applies to the Research and Development (R&D) and Quality Control (QC) departments responsible for monitoring and adjusting the pH of ointments during formulation trials and manufacturing scale-up.
3. Responsibilities
- Formulation Scientist: Adjusts and optimizes pH levels during formulation development.
- Quality Control (QC) Analyst: Conducts pH testing and verifies compliance with specifications.
- Quality Assurance (QA) Personnel: Ensures compliance with standard procedures and regulatory guidelines.
- R&D Head: Reviews and approves pH adjustment reports before finalizing formulations.
4. Accountability
The R&D and QC Managers are accountable for ensuring that pH adjustment is conducted per regulatory and quality standards.
5. Procedure
5.1 Selection of pH Range
- Determine the optimal pH range for the ointment based on:
- Skin compatibility (typically 4.5 – 7.0)
- API stability requirements
- Preservative efficacy
- Ensure that the target pH range is specified in the formulation protocol.
5.2 Preparation of Sample for pH Measurement
- Weigh 1 g of the ointment sample.
- Disperse in 10 mL of distilled water or a suitable solvent.
- Stir for 5 minutes using a magnetic stirrer.
- Allow the sample to equilibrate at room temperature (25°C ± 2°C).
5.3 pH Measurement
- Calibrate the pH meter using standard buffer solutions (pH 4.0, 7.0, and 10.0).
- Immerse the pH electrode into the sample solution.
- Record the pH reading once it stabilizes.
- Rinse the electrode with distilled water after each measurement.
5.4 Adjustment of pH
- If pH is lower than the target range:
- Add a small amount (0.1 – 1.0% w/w) of a suitable alkaline agent (e.g., sodium hydroxide, triethanolamine).
- Mix thoroughly and recheck the pH.
- Repeat until the pH reaches the desired range.
- If pH is higher than the target range:
- Add a small amount (0.1 – 1.0% w/w) of an acidic agent (e.g., citric acid, lactic acid).
- Mix thoroughly and recheck the pH.
- Repeat until the pH reaches the desired range.
5.5 Confirmation and Stability Testing
- Confirm the final pH by measuring triplicate samples.
- Store samples at different stability conditions:
- 25°C ± 2°C / 60% RH
- 40°C ± 2°C / 75% RH
- Refrigerated conditions (2-8°C)
- Monitor pH over a period of time to ensure stability.
5.6 Documentation and Reporting
- Record all pH test results in the pH Adjustment Log.
- Summarize findings in the pH Adjustment Report.
- Obtain approval from the R&D Head and QA before finalizing pH parameters.
6. Abbreviations
- QC – Quality Control
- QA – Quality Assurance
- RH – Relative Humidity
- USP – United States Pharmacopeia
- BP – British Pharmacopeia
- IP – Indian Pharmacopeia
7. Documents
- pH Adjustment Log (Annexure-1)
- pH Adjustment Report (Annexure-2)
8. References
- USP <791> pH Measurement Guidelines
- ICH Q1A (R2) Stability Testing Guidelines
- WHO GMP Guidelines for Pharmaceutical Manufacturing
- 21 CFR Part 211 – Current Good Manufacturing Practices
9. SOP Version
Version 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: pH Adjustment Log
| Date | Batch Number | Initial pH | Adjustment Agent | Final pH | Verified By |
|---|---|---|---|---|---|
| 01/02/2025 | OINT-001 | 4.2 | Triethanolamine | 5.5 | QA Officer |
| 02/02/2025 | OINT-002 | 7.8 | Citric Acid | 6.8 | QA Officer |
Annexure-2: pH Adjustment Report
| Date | Batch Number | Initial pH | Target pH | Final pH | Final Status |
|---|---|---|---|---|---|
| 01/02/2025 | OINT-001 | 4.2 | 5.5-7.0 | 5.5 | Pass |
| 02/02/2025 | OINT-002 | 7.8 | 5.5-7.0 | 6.8 | Pass |
12. Revision History:
| Revision Date | Revision No. | Details of Revision | Reason for Revision | Approved By |
|---|---|---|---|---|
| 01/01/2024 | 1.0 | Initial Version | New SOP | QA Head |
| 01/02/2025 | 2.0 | Updated SOP Format | Standardization of Document | QA Head |