to formulation and development personnel involved in screening APIs for chemical, physical, and microbiological compatibility with polymers, gelling agents, preservatives, and other excipients used in semi-solid gel formulations.

3. Responsibilities

• Formulation Scientist: To conduct compatibility studies and record data.
• Analytical Chemist: To analyze test samples for degradation, pH, viscosity, and appearance.
• R&D Manager: To review and approve compatibility results and decide on go/no-go for formulation.

4. Accountability

The Head – R&D shall be accountable for the implementation and effectiveness of this SOP.

5. Procedure

5.1 API and Excipient Selection

1. Prepare a list of target APIs with known properties (e.g., solubility, pKa, molecular weight, etc.).
2. Shortlist gel excipients and bases from previous formulation experience or supplier data.
3. Review available compatibility data from literature and databases.

5.2 Preparation of Binary Mixtures

1. Mix API with each excipient in 1:1 ratio by weight.
2. Blend uniformly using a mortar and pestle or V-blender.
3. Store each mixture in closed, labeled containers.

5.3 Storage Conditions

1. Keep samples at three conditions for 14 days:
   • Room Temperature (25°C ± 2°C, 60% RH)
   • Accelerated (40°C ± 2°C, 75% RH)
   • Refrigerated (5°C ± 3°C)

5.4 Evaluation Parameters

1. Appearance: Observe visually for discoloration, phase separation, or crystal formation.
2. pH: Measure using calibrated pH meter.
3. Viscosity: Use Brookfield viscometer.
4. Assay: Conduct chemical analysis using validated HPLC or UV method.
5. FTIR Analysis: Detect chemical interactions using Fourier-Transform Infrared Spectroscopy.

5.5 Acceptance Criteria

• No significant change in appearance, odor, or viscosity.
• pH change not more than ±0.5 units.
• API assay within 95–105% of label claim.
• No new peaks or shifts in FTIR spectra suggestive of incompatibility.

5.6 Documentation

1. Use Compatibility Evaluation Form (Annexure-1) to document observations and test results.
2. Summarize data in API Compatibility Summary Report (Annexure-2).

5.7 Decision Making

1. If results meet all acceptance criteria, the API-excipient combination may proceed to prototype formulation.
2. If results fail criteria, re-screen with alternative excipients or modify concentration.

6. Abbreviations

• API: Active Pharmaceutical Ingredient
• SOP: Standard Operating Procedure
• FTIR: Fourier-Transform Infrared Spectroscopy
• HPLC: High-Performance Liquid Chromatography

7. Documents

1. API Compatibility Evaluation Form – Annexure-1
2. API Compatibility Summary Report – Annexure-2
3. Raw Data Sheets and FTIR Spectra – Annexure-3

8. References

• ICH Q8(R2): Pharmaceutical Development
• ICH Q1A(R2): Stability Testing of New Drug Substances and Products
• Pharmaceutical Preformulation and Formulation Handbook

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation	Jr. Production Chemist	QA Executive	Head – Manufacturing
Department	Gel Manufacturing	Quality Assurance	Manufacturing

11. Annexures

Annexure-1: API Compatibility Evaluation Form

API	Excipient	Ratio	Condition	Observation	Assay (%)
Drug A	Carbopol 940	1:1	40°C	No change	99.2

Annexure-2: API Compatibility Summary Report

API	Compatible Excipients	Remarks	Recommended for Prototype
Drug A	Carbopol 940, HPMC	Stable and compatible	Yes

Annexure-3: Raw Data Summary

Sample ID	pH	Viscosity (cps)	FTIR Result
A001	6.2	18000	No interaction

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/06/2022	1.0	Initial version	New SOP	Head – R&D
02/06/2025	2.0	Added FTIR & expanded conditions	Process enhancement	Head – R&D