Procedure for Mixing Active Ingredients in Ointment Base
| Department | Production/Quality Assurance (QA)/Research and Development (R&D) |
|---|---|
| SOP No. | SOP/Ointment/024 |
| 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 establish a standardized method for the uniform mixing of active ingredients into the ointment base. Proper mixing ensures even distribution of active pharmaceutical ingredients (APIs), stability, and efficacy of the final product.
2. Scope
This SOP applies to all personnel responsible for blending APIs with the base in the ointment manufacturing process.
3. Responsibilities
- Production Supervisor: Ensures proper execution of the mixing process.
- Machine Operator: Operates and monitors the mixing equipment.
- Quality Assurance (QA) Personnel: Verifies uniformity and process compliance.
- R&D Scientist: Provides guidance on mixing parameters during formulation development.
4. Accountability
The Production and QA Managers are accountable for ensuring that the mixing process is conducted as per GMP guidelines and documented correctly.
5. Procedure
5.1 Pre-Mixing Preparations
- Ensure the mixing vessel and all equipment are clean and sanitized.
- Check that all required ingredients are weighed accurately as per the Batch Manufacturing Record (BMR).
- Verify the temperature and viscosity of the melted base before incorporating active ingredients.
5.2 Addition of Active Ingredients
- Slowly add the active ingredient(s)
into the pre-heated ointment base.
Ensure uniform dispersion by adding in increments while mixing continuously.
Use a homogenizer if required to ensure fine particle distribution.
5.3 Mixing Parameters
- Maintain a controlled mixing speed to avoid air entrapment.
- Monitor temperature and adjust as required to prevent degradation.
- Continue mixing for the time specified in the formulation protocol.
- Perform a visual inspection to check for consistency.
5.4 Homogenization (If Required)
- If further homogenization is needed, pass the mixture through a homogenizer.
- Ensure particle size reduction to achieve a smooth consistency.
- Document homogenization settings (speed, pressure, time).
5.5 In-Process Quality Control Checks
- Take a representative sample and check for uniformity.
- Perform pH and viscosity measurements.
- Ensure compliance with batch specifications before proceeding to cooling.
5.6 Cooling and Holding
- Gradually reduce the temperature while maintaining gentle mixing.
- Prevent crystallization or separation by following controlled cooling parameters.
- Hold the mixture at the specified temperature before transfer to filling equipment.
5.7 Documentation and Approval
- Record all mixing parameters in the Mixing Log.
- QA must verify the mixed batch before filling.
- Label the final bulk mixture as “Ready for Filling.”
6. Abbreviations
- BMR – Batch Manufacturing Record
- API – Active Pharmaceutical Ingredient
- QA – Quality Assurance
- GMP – Good Manufacturing Practices
7. Documents
- Mixing Log (Annexure-1)
- In-Process Quality Control Report (Annexure-2)
8. References
- WHO GMP Guidelines for Pharmaceutical Manufacturing
- 21 CFR Part 211 – Current Good Manufacturing Practices
- Equipment Manufacturer Guidelines
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 Log
| Date | Batch Number | Active Ingredient | Mixing Speed (RPM) | Temperature (°C) | Time (Min) | Verified By |
|---|---|---|---|---|---|---|
| 01/02/2025 | SOP/Ointment/001 | API-A | 500 | 65°C | 30 | QA Officer |
| 02/02/2025 | SOP/Ointment/002 | API-B | 600 | 70°C | 40 | QA Officer |
Annexure-2: In-Process Quality Control Report
| Date | Batch Number | Test Parameter | Specification | Result | Final Status |
|---|---|---|---|---|---|
| 01/02/2025 | SOP/Ointment/001 | Viscosity | 1000-2000 cP | 1500 cP | Pass |
| 02/02/2025 | SOP/Ointment/002 | pH | 5.5-7.0 | 6.2 | Pass |
12. Revision History:
| Revision Date | Revision No. | Details of Revision | Reason for Revision | Approved By |
|---|---|---|---|---|
| 01/01/2024 | 1.0 | Initial Version | New SOP | QA Head |
| 01/02/2025 | 2.0 | Updated SOP Format | Standardization of Document | QA Head |