Standard Operating Procedure for Blending Process for Uniform Distribution of Excipients

Department	Tablet
SOP No.	SOP/TAB/016/2025
Supersedes	SOP/TAB/016/2022
Page No.	Page 1 of 8
Issue Date	29/04/2025
Effective Date	04/05/2025
Review Date	29/04/2026

1. Purpose

This SOP defines the process for blending excipients in tablet manufacturing to ensure uniform distribution and homogeneity of the powder mixture before compression.

2. Scope

This SOP applies to the blending of excipients for tablet manufacturing, covering the equipment setup, blending process, and quality control checks during and after blending.

3. Responsibilities

• Manufacturing Personnel: Responsible for operating the blending equipment, ensuring uniformity in the blend, and following the specified parameters.
• Quality Control (QC): Ensures the homogeneity of the blend through sampling and testing, and ensures compliance with specifications.
• Quality Assurance (QA): Ensures that the blending process follows the SOP and meets regulatory and quality standards, reviewing records for compliance.

4. Accountability

The Production Manager is accountable for the blending process, ensuring that all excipients are uniformly blended. The QA Manager is responsible for ensuring that the blending process meets the required standards.

5. Procedure

5.1 Blending Equipment Setup

1. Ensure that the blender (e.g., V-Blender, Double Cone Blender) is clean and free of any residual material from previous batches.
2. Verify that the equipment is calibrated and functioning properly, including the motor speed and blending time controls.
3. Check that all required excipients, including active pharmaceutical ingredients (APIs) and fillers, are available and within their specified limits for use.
4. Ensure that all excipients are sifted or sieved to remove any lumps or large particles before starting the blending process.

5.2 Loading Excipients into the Blender

1. Measure the required amount of excipients according to the batch size and formulation specifications.
2. Ensure that the materials are loaded into the blender evenly to avoid overloading or uneven blending.
3. Use proper handling techniques to prevent contamination or spillage of excipients during loading.
4. Verify that the excipient batch numbers, expiry dates, and Certificates of Analysis (CoA) are correct and within the specified limits.

5.3 Blending Process

1. Start the blender and set the parameters (e.g., blending speed, time) according to the product specifications for uniform mixing.
2. Monitor the blending process to ensure that the mixture is homogenous and that no segregation of excipients occurs during blending.
3. Ensure that the blender is operating within the specified speed and time limits, preventing under or over-mixing.
4. Allow the blend to mix for the required amount of time as specified in the formulation guide, typically 10-20 minutes.
5. If necessary, stop the blending process periodically to check for uniformity and ensure no clumping or uneven blending of materials.

5.4 In-Process Quality Control

1. Take samples at regular intervals during the blending process to check for uniformity and consistency in the blend.
2. Conduct testing to check for uniformity of distribution, such as content uniformity testing or drug uniformity sampling, to ensure that active ingredients are evenly distributed.
3. Check for any lumps or foreign particles in the blend, and if present, correct the process by adjusting the blending speed or time.
4. Record results of all in-process quality checks, including sample test results, in the batch record (Annexure-1).

5.5 Completion of Blending Process

1. After the blending process is complete, stop the blender and verify that the blend meets the required homogeneity criteria.
2. Inspect the blend visually for any discrepancies, such as color or particle size variation, and ensure that no segregation has occurred.
3. Ensure that the blend is free from any contamination or foreign particles.
4. Record the final weight of the blend to ensure it meets the batch specifications.

5.6 Transfer to the Next Process

1. Once the blend has passed the required quality checks, transfer the material to the next stage of the tablet manufacturing process, such as tablet compression or encapsulation.
2. Ensure that the blend is transferred in clean, properly labeled containers to prevent contamination and ensure traceability.
3. Record the transfer details in the batch record to maintain proper documentation of the manufacturing process.

5.7 Equipment Shutdown and Cleaning

1. Once the blending process is completed, turn off the equipment and proceed with cleaning according to the equipment cleaning SOP.
2. Ensure that all components of the blender that came into contact with the excipients (e.g., blender drum, mixing blades) are thoroughly cleaned to prevent cross-contamination between batches.
3. Document the cleaning process and ensure that all cleaning steps are properly recorded in the cleaning log (Annexure-2).

5.8 Documentation and Record-Keeping

1. Document the entire blending process, including blending time, speed, excipient details, sample test results, and any deviations from the standard process in the batch record.
2. Ensure that all records are reviewed, signed off, and stored for regulatory compliance and future reference.
3. Ensure that any deviations or corrective actions taken during the blending process are documented and reviewed by QA.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• CoA: Certificate of Analysis

7. Documents

1. Batch Record (Annexure-1)
2. Equipment Cleaning Log (Annexure-2)

8. References

• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• EU GMP Guidelines Part I – Basic Requirements for Medicinal Products
• ICH Q7 – Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Batch Record

Batch Number	Excipients Used	Blend Time	Blend Speed	Uniformity Test Results	Remarks
Batch 001	Cellulose, Lactose	15 min	45 RPM	Pass	Within specifications
Batch 002	Starch, Magnesium Stearate	20 min	40 RPM	Pass	Minor variation, resolved

Annexure-2: Equipment Cleaning Log

Equipment	Cleaning Date	Cleaning Method	Personnel
V-Blender	28/04/2025	Washing with detergent and rinsing with water	John Doe
V-Blender	29/04/2025	Washing with detergent and rinsing with water	Jane Smith

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
01/01/2024	1.0	Initial Version	New SOP Creation	QA Head
01/02/2025	2.0	Updated Blending Parameters	Optimization of Blend Uniformity Process	QA Head