Procedure for Preventing Air Entrapment During Mixing
| Department | Manufacturing/Production/Quality Assurance (QA)/Quality Control (QC)/Research and Development (R&D) |
|---|---|
| SOP No. | SOP/Ointment/196 |
| 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 define a systematic process for preventing air entrapment during the mixing of ointments. Air entrapment can lead to product instability, batch inconsistency, and reduced efficacy of the final formulation.
2. Scope
This SOP applies to all personnel involved in the handling, mixing, and quality control of ointment formulations in the Manufacturing, Production, Quality Assurance (QA), Quality Control (QC), and Research and Development (R&D) departments.
3. Responsibilities
- Production Supervisor: Ensures adherence to anti-air entrapment procedures.
- Process Operator: Monitors and controls mixing conditions to minimize air incorporation.
- QA Officer: Verifies that mixing conditions meet process control guidelines.
- QC Analyst: Conducts visual and microscopic analysis to detect air pockets.
- Maintenance Engineer: Ensures vacuum systems and degassing equipment are functioning properly.
4. Accountability
The Production Manager is accountable for ensuring that all air entrapment prevention procedures comply with GMP, FDA, ICH, WHO, and company policies.
5. Procedure
5.1 Identifying Causes of Air Entrapment
- Common causes of air entrapment in ointment mixing:
- High-speed mixing without controlled vacuum application.
- Rapid ingredient addition leading
to turbulence.
Improper positioning of mixing blades or agitators.
Insufficient deaeration time before filling.
Document identified risks in the **Air Entrapment Risk Assessment Log (Annexure-1).**
5.2 Process Optimization to Minimize Air Entrapment
- Adjust **mixing speeds based on batch size and viscosity**:
- Initial blending: **50-100 RPM**
- Homogenization: **200-400 RPM under vacuum**
- Final blending: **30-60 RPM with slow agitation**
- Introduce ingredients slowly to prevent excessive turbulence.
- Use **vacuum mixing (negative pressure -0.8 bar) whenever possible.**
- Document optimized conditions in the **Process Optimization Log (Annexure-2).**
5.3 Deaeration Techniques
- Use vacuum degassing systems to remove trapped air after mixing.
- Ensure the product is **held under vacuum for 5-10 minutes** before filling.
- Minimize manual interventions that may introduce air into the batch.
- Record all deaeration process parameters in the **Deaeration Log (Annexure-3).**
5.4 Post-Mixing Quality Control
- Conduct **visual inspection** for air pockets or foaming.
- Use **microscopic analysis** to confirm uniform consistency.
- Verify bulk density and viscosity before proceeding to filling.
- Record all test results in the **Quality Control Testing Log (Annexure-4).**
6. Abbreviations
- GMP – Good Manufacturing Practices
- QA – Quality Assurance
- QC – Quality Control
- ICH – International Council for Harmonisation
- FDA – Food and Drug Administration
7. Documents
- Air Entrapment Risk Assessment Log (Annexure-1)
- Process Optimization Log (Annexure-2)
- Deaeration Log (Annexure-3)
- Quality Control Testing Log (Annexure-4)
8. References
- ICH Q8 – Pharmaceutical Development Guidelines
- FDA Guidance on Mixing and Homogenization
- WHO Guidelines on Manufacturing Process Control
9. SOP Version
Version 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Air Entrapment Risk Assessment Log
| Date | Batch No. | Identified Risk | Preventive Action | QA Approval |
|---|---|---|---|---|
| 03/02/2025 | OINT-5001 | High-speed agitation | Reduced RPM | Approved |
Annexure-2: Process Optimization Log
| Date | Batch No. | Process Adjustment | Outcome | QA Approval |
|---|---|---|---|---|
| 03/02/2025 | OINT-5001 | Vacuum applied | Entrapment reduced | Approved |
Annexure-3: Deaeration Log
| Date | Batch No. | Vacuum Applied (bar) | Deaeration Time (min) | QA Approval |
|---|---|---|---|---|
| 04/02/2025 | OINT-6001 | -0.8 | 10 | Approved |
Annexure-4: Quality Control Testing Log
| Date | Batch No. | Air Pockets Detected | Bulk Density (g/mL) | QA Approval |
|---|---|---|---|---|
| 04/02/2025 | OINT-6001 | No | 1.02 | Approved |
12. Revision History
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 03/02/2025 | 2.0 | Expanded Air Entrapment Prevention Measures | Regulatory Compliance | QA Head |
| 01/01/2024 | 1.0 | Initial SOP | New SOP Implementation | QA Head |