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