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