Procedure for Compatibility Testing of Ingredients in Ointments
| Department | Research and Development (R&D)/Quality Control |
|---|---|
| SOP No. | FD-014 |
| 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 establish a systematic approach for evaluating the compatibility of ingredients in ointment formulations. This ensures the stability, efficacy, and safety of the final product.
2. Scope
This SOP applies to all active pharmaceutical ingredients (APIs), excipients, preservatives, and stabilizers used in ointment formulations. It includes procedures for physical, chemical, and thermal compatibility testing.
3. Responsibilities
- Formulation Scientist: Conducts compatibility studies and analyzes results.
- Analytical Chemist: Performs analytical tests on ingredient mixtures.
- Quality Control (QC) Analyst: Verifies test results and ensures compliance with specifications.
- Quality Assurance (QA) Personnel: Reviews and approves compatibility test reports.
- R&D Head: Approves final formulation based on compatibility findings.
4. Accountability
The R&D and QC Managers are accountable for ensuring that all compatibility testing is conducted per regulatory and quality standards.
5. Procedure
5.1 Selection of Ingredients for Compatibility Testing
- Select the API and all excipients to be tested.
- Ensure each ingredient is sourced from approved vendors.
- Document the physical and chemical properties of each component.
5.2 Preparation of Ingredient Mixtures
- Prepare binary and multiple-component mixtures of
API and excipients.
Ensure uniform blending using a mortar and pestle or mechanical mixer.
Divide samples for different storage conditions.
5.3 Physical Compatibility Testing
- Observe color, texture, and phase separation under normal storage conditions.
- Monitor for crystal formation, precipitation, or sedimentation.
- Record any physical changes in the Compatibility Testing Log.
5.4 Chemical Compatibility Testing
- Analyze samples using FTIR spectroscopy to detect interactions.
- Conduct High-Performance Liquid Chromatography (HPLC) tests for degradation products.
- Measure pH changes over time.
- Compare results with reference spectra and specifications.
5.5 Thermal Compatibility Testing
- Store samples at different conditions:
- 25°C ± 2°C / 60% RH
- 40°C ± 2°C / 75% RH
- Refrigerated conditions (2-8°C)
- Monitor samples for physical and chemical changes at weekly intervals.
- Document findings in the Stability Testing Report.
5.6 Data Analysis and Interpretation
- Compare test results against standard limits.
- Identify any ingredient incompatibilities.
- Recommend alternative excipients if necessary.
5.7 Documentation and Reporting
- Record all observations in the Compatibility Testing Log.
- Prepare a Compatibility Testing Report summarizing results and recommendations.
- Obtain approval from QA before finalizing the formulation.
6. Abbreviations
- API – Active Pharmaceutical Ingredient
- QC – Quality Control
- QA – Quality Assurance
- HPLC – High-Performance Liquid Chromatography
- FTIR – Fourier Transform Infrared Spectroscopy
- RH – Relative Humidity
7. Documents
- Compatibility Testing Log (Annexure-1)
- Compatibility Testing Report (Annexure-2)
8. References
- ICH Q1A (R2) Stability Testing Guidelines
- USP <1058> Analytical Instrument Qualification
- 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: Compatibility Testing Log
| Date | Batch Number | Ingredient Combination | Observed Changes | Verified By |
|---|---|---|---|---|
| 01/02/2025 | CT-001 | API + Emulsifier | No Change | QA Officer |
| 02/02/2025 | CT-002 | API + Preservative | Color Change | QA Officer |
Annexure-2: Compatibility Testing Report
| Date | Batch Number | Compatibility Parameter | Specification | Result | Final Status |
|---|---|---|---|---|---|
| 01/02/2025 | CT-001 | Viscosity | 1000-2000 cP | 1500 cP | Pass |
| 02/02/2025 | CT-002 | pH | 5.5-7.5 | 8.0 | Fail |
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 |