Procedure for Particle Size Reduction in Ointment Manufacturing

Department	Production/Quality Assurance (QA)/Research and Development (R&D)
SOP No.	SOP/Ointment/026
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 process for reducing the particle size of active pharmaceutical ingredients (APIs) and excipients in ointment manufacturing. Proper particle size reduction enhances uniformity, improves stability, and ensures better product efficacy.

2. Scope

This SOP applies to all personnel involved in the particle size reduction process using mills, homogenizers, or other mechanical size reduction equipment.

3. Responsibilities

• Production Supervisor: Ensures the particle size reduction process follows defined parameters.
• Machine Operator: Operates and monitors the milling or homogenization equipment.
• Quality Assurance (QA) Personnel: Verifies uniformity and compliance with specifications.
• R&D Scientist: Defines particle size requirements for different formulations.

4. Accountability

The Production and QA Managers are accountable for ensuring that particle size reduction is conducted as per GMP guidelines and documented properly.

5. Procedure

5.1 Pre-Processing Checks

• Ensure the milling/homogenization equipment is clean and calibrated.
• Verify that the raw materials are within the required moisture and temperature specifications.
• Confirm the target particle size distribution from the Batch Manufacturing Record (BMR).

5.2 Selection of Size Reduction Method

• Ball Milling: Used for reducing coarse particles.
• Jet Milling: Used for finer particle reduction without heat generation.
• High-Shear Homogenization: Used for reducing particle size in liquid formulations.

5.3 Particle Size Reduction Process

• Feed the materials into the milling/homogenization system.
• Set the milling parameters such as speed, pressure, and time as per formulation requirements.
• Monitor the equipment for uniform particle size reduction.

5.4 Sampling and In-Process Quality Control

• Take a sample at predefined intervals.
• Check for particle size distribution using a particle size analyzer.
• Verify that the particle size is within the acceptable range (e.g., 10-50 microns).

5.5 Final Verification

• Inspect for agglomerates or oversized particles.
• Compare results with standard specifications before proceeding to mixing.

5.6 Documentation and Approval

• Record all process parameters in the Particle Size Reduction Log.
• QA must verify and approve the reduced particle batch before further processing.
• Label the processed material as “Ready for Use.”

6. Abbreviations

• GMP – Good Manufacturing Practices
• QA – Quality Assurance
• R&D – Research and Development
• BMR – Batch Manufacturing Record

7. Documents

• Particle Size Reduction 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: Particle Size Reduction Log

Date	Batch Number	Reduction Method	Initial Size (µm)	Final Size (µm)	Verified By
01/02/2025	SOP/Ointment/001	Jet Milling	100	30	QA Officer
02/02/2025	SOP/Ointment/002	Ball Milling	200	50	QA Officer

Annexure-2: In-Process Quality Control Report

Date	Batch Number	Test Parameter	Specification	Result	Final Status
01/02/2025	SOP/Ointment/001	Particle Size Distribution	10-50 µm	30 µm	Pass
02/02/2025	SOP/Ointment/002	Agglomerate Content	<1%	0.5%	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