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 establish a systematic procedure for preventing aeration during the mixing of elixir formulations, which can lead to product instability, foaming, oxidation, and dosing inconsistencies.

2. Scope

This SOP applies to all mixing processes involved in elixir manufacturing where aeration control is critical to maintaining product quality and uniformity.

3. Responsibilities

• Manufacturing Operator:
  • Operate mixing equipment in a manner that minimizes air entrapment.
  • Follow mixing speed and agitation sequence as per BMR instructions.
• Production Supervisor:
  • Ensure equipment design and mixing parameters are aeration-safe.
  • Verify agitation speed and impeller settings.
• QA Officer:
  • Monitor visual indicators of aeration (bubbles, foam) during mixing and ensure compliance to SOP.

4. Accountability

The Production Head is accountable for ensuring that all mixing operations are carried out in a manner that avoids aeration and preserves product quality.

5. Procedure

5.1 Equipment and Setup

1. Use bottom-entry or low-shear mixers whenever possible to minimize vortex formation.
2. Ensure impellers are properly positioned and not exposed above the liquid surface.
3. Ensure tanks are filled to at least 70% of their working capacity before initiating high-speed mixing.

5.2 Agitation Control

1. Start mixing at low RPM (e.g., 20–40) and gradually increase if necessary.
2. Avoid vigorous agitation at low liquid volumes to prevent vortexing.
3. Monitor vortex depth visually; it should not exceed 1/4 of liquid depth.
4. If a vortex forms, reduce speed immediately and adjust impeller depth.

5.3 Addition of Ingredients

1. Add powders or concentrates slowly into the vortex area or through a submerged funnel to reduce splashing and air intake.
2. For volatile or foaming agents (e.g., surfactants, ethanol), reduce agitation to minimal levels during addition.
3. Keep vessel covered during addition to reduce air turbulence.

5.4 Visual Inspection

1. Check for presence of bubbles, foam, or milky consistency.
2. If foam is observed:
   • Pause mixing and allow solution to settle.
   • Skim off foam if necessary using sterile utensils.
3. Document findings and corrective actions in the Aeration Control Log (Annexure-1).

5.5 Post-Mixing Measures

1. Allow batch to stand for at least 15 minutes post-mixing before filtration to allow trapped air to escape.
2. Do not proceed to filtration or filling if signs of aeration persist.

6. Abbreviations

• SOP: Standard Operating Procedure
• BMR: Batch Manufacturing Record
• QA: Quality Assurance
• RPM: Revolutions Per Minute

7. Documents

1. Aeration Control Log (Annexure-1)
2. Mixing Parameter Sheet (Annexure-2)
3. Foam Observation Checklist (Annexure-3)

8. References

• WHO GMP Guidelines for Liquid Oral Preparations
• ICH Q8(R2) – Pharmaceutical Development

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Aeration Control Log

Date	Batch No.	Observed Issue	Corrective Action	Operator	Verified By
11/04/2025	ELX-1012	Foam formation	Agitation stopped, foam removed	Rajesh Kumar	Sunita Reddy

Annexure-2: Mixing Parameter Sheet

Batch No.	Start Time	End Time	RPM	Impeller Type	Remarks
ELX-1012	09:00 AM	09:45 AM	60	Anchor	No vortex

Annexure-3: Foam Observation Checklist

Time	Observation	Action Taken	Checked By
09:45 AM	Minimal foam present	Allowed to settle	Sunita Reddy

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
01/01/2024	1.0	Initial SOP Release	New SOP	QA Head
11/04/2025	2.0	Included Vortex Depth Limit and Foam Checklist	Process Optimization	QA Head