Elixir Department: SOP for Solubility Testing at Intermediate Stages – V 2.0

Standard Operating Procedure for Solubility Testing at Intermediate Stages in Elixir Manufacturing

Department	Elixir Department
SOP No.	SOP/ELX/197/2025
Supersedes	SOP/ELX/197/2022
Page No.	Page 1 of 8
Issue Date	11/04/2025
Effective Date	15/04/2025
Review Date	11/04/2026

1. Purpose

To define a standardized procedure for performing solubility testing of active ingredients and excipients at intermediate stages of elixir manufacturing to ensure complete dissolution and avoid precipitation during further processing.

2. Scope

This SOP applies to all elixir batches that require confirmation of solubility of active ingredients and selected excipients after their addition during processing, and prior to bulk completion.

3. Responsibilities

Production Operator:
- Collect samples for solubility testing as per stage-wise instructions.
QC Analyst:
- Perform solubility checks using visual inspection, centrifugation, or filtration, and document findings.
QA Officer:
- Ensure compliance with sampling and testing procedures and review results.

4. Accountability

The Production Head is accountable for correct sampling. QC Head is responsible for test accuracy. QA is accountable for documentation and compliance verification.

5. Procedure

5.1 Sampling

for Solubility Testing

Sample after complete addition and mixing of the API or excipient in the manufacturing tank.
Collect 50 mL of the sample in a clean, dry, transparent glass vial.
Label with product name, batch number, stage, date, and “Solubility Sample.”
Transport the sample to the QC lab immediately to avoid temperature-induced solubility shifts.

5.2 Testing Procedure

Visual Inspection: Hold the vial against white and black backgrounds and observe for undissolved particles, turbidity, or haze.
Filtration Method:
- Filter 10 mL of the sample through a 0.45 µm filter paper.
- Check for residue on the filter. No visible residue indicates complete solubility.
Centrifugation Method:
- Centrifuge 10 mL of the sample at 3000 rpm for 10 minutes.
- Check for sediment or phase separation.

5.3 Acceptance Criteria

The solution must appear clear or as per product specifications.
No visible undissolved particles, sediments, or phase separation should be observed.
If undissolved matter is present, notify Production and QA for reprocessing or mixing extension.

5.4 Corrective Actions for Non-Conformance

Hold the batch and inform QA.
Repeat mixing and re-test solubility.
If solubility is not achieved after reprocessing, escalate to product development and initiate deviation handling.

5.5 Documentation

Record test results in the Solubility Testing Logbook (Annexure-1).
Include batch details, test method used, observation, interpretation, and analyst initials.
Attach supporting evidence such as filter papers (if applicable) to the batch documentation file.

6. Abbreviations

SOP: Standard Operating Procedure
QC: Quality Control
QA: Quality Assurance
API: Active Pharmaceutical Ingredient
RPM: Revolutions Per Minute

7. Documents

Solubility Testing Logbook (Annexure-1)
Batch Manufacturing Record (BMR)
Analytical Method Sheet

8. References

ICH Q6A – Specifications: Test Procedures and Acceptance Criteria
WHO TRS 986 – GMP for Pharmaceuticals
21 CFR Part 211 – Subpart I: Laboratory Controls

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Solubility Testing Logbook

Date	Batch No.	Stage	Test Method	Observation	Result	Analyst	QA Verified
11/04/2025	ELX-0425-016	Post-API Addition	Filtration	No Residue on Filter	Pass	Rajesh Kumar	Sunita Reddy

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
01/01/2024	1.0	Initial Release	New SOP	QA Head
11/04/2025	2.0	Added centrifugation method and corrective action flow	Process Enhancement	QA Head