Standard Operating Procedure for Prevention of Aeration During Mixing in Elixir Manufacturing
| Department | Elixir Department |
|---|---|
| SOP No. | SOP/ELX/067/2025 |
| Supersedes | SOP/ELX/067/2022 |
| 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 the procedure for preventing aeration during the mixing of elixir formulations, ensuring product clarity, stability, and prevention of oxidative degradation.
2. Scope
This SOP applies to all elixir formulations mixed using mechanical or magnetic stirrers in the Elixir Department, especially those containing alcohol, volatile agents, or oxidation-sensitive APIs.
3. Responsibilities
- Production Operator:
- Set and monitor agitation speed to minimize vortex formation.
- Ensure proper flow direction and baffling to reduce air entrapment.
- Production Supervisor:
- Verify mixing parameters and ensure SOP compliance.
- QA Officer:
- Inspect batches for signs of aeration and confirm corrective actions if needed.
4. Accountability
The Production Head is accountable for ensuring that aeration control is implemented during mixing operations and deviations are addressed as per CAPA.
5. Procedure
5.1 Equipment Setup
- Ensure use of a mixing tank
with bottom entry agitator or deflector baffles if available.
Verify that impeller type (e.g., marine propeller, anchor blade) is suitable for low shear mixing.
Ensure the tank is filled to at least 60% of its working volume before starting agitation to avoid vortex formation.
5.2 Agitation Control
- Start mixing at low RPM (e.g., 40–60 RPM).
- Avoid rapid changes in agitation speed that could pull air into the solution.
- Gradually increase speed if necessary, but do not exceed 100 RPM unless validated for the product.
5.3 Ingredient Addition Technique
- Add ingredients close to the tank wall instead of directly into the vortex.
- Use submerged addition where feasible—add materials using dip tubes or bottom entry ports to reduce splashing and air incorporation.
5.4 Observation and Inspection
- Visually check the batch for signs of foam or bubbles during and after mixing.
- If bubbles are observed:
- Reduce agitation speed immediately.
- Allow the solution to stand until air escapes naturally.
- In critical cases, apply vacuum de-aeration (if validated).
5.5 Documentation
- Record mixing speed, duration, temperature, and aeration observations in the Mixing Control Log (Annexure-1).
- If de-aeration was required, document in the De-Aeration Log (Annexure-2).
6. Abbreviations
- SOP: Standard Operating Procedure
- QA: Quality Assurance
- CAPA: Corrective and Preventive Action
- RPM: Revolutions Per Minute
7. Documents
- Mixing Control Log (Annexure-1)
- De-Aeration Log (Annexure-2)
- BMR – Mixing Section
8. References
- ICH Q8(R2) – Pharmaceutical Development
- WHO GMP Guidelines – Liquid Dosage Manufacturing
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Mixing Control Log
| Date | Batch No. | RPM | Duration (min) | Aeration Observed | Operator | Verified By |
|---|---|---|---|---|---|---|
| 11/04/2025 | ELX-1012 | 60 | 30 | No | Rajesh Kumar | Sunita Reddy |
Annexure-2: De-Aeration Log
| Date | Batch No. | Method Used | Duration | Remarks | Approved By |
|---|---|---|---|---|---|
| 11/04/2025 | ELX-1012 | Natural Standing | 10 min | Minor foam resolved | 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 | Included De-Aeration Log and Preventive Steps | GMP Enhancement | QA Head |