Capsule: SOP for Mixing and Blending of APIs and Excipients – V 2.0

Auditor

2 weeks ago

Standard Operating Procedure for Mixing and Blending of APIs and Excipients

Department	Capsule Manufacturing
SOP No.	SOP/CM/052/2025
Supersedes	SOP/CM/052/2022
Page No.	Page 1 of 6
Issue Date	01/02/2025
Effective Date	05/02/2025
Review Date	01/02/2026

1. Purpose

The purpose of this SOP is to outline the procedure for mixing and blending Active Pharmaceutical Ingredients (APIs) with excipients in capsule formulation. Proper mixing and blending are crucial to ensure uniformity, consistency, and the desired efficacy of the final product.

2. Scope

This SOP applies to the mixing and blending process of APIs and excipients used in the formulation of capsule products. It covers the selection of materials, equipment, blending process, and quality control checks to ensure the homogeneous distribution of ingredients.

3. Responsibilities

Formulation Development Team: Responsible for selecting the APIs and excipients, and designing the formulation with the appropriate ratios for the blending process.
Manufacturing Team: Responsible for ensuring that the mixing and blending process is carried out as per the SOP, with the correct equipment and environmental conditions.
Quality Control (QC) Team: Responsible for testing the blended materials to ensure uniformity, consistency, and compliance with specifications, such as content uniformity and moisture content.
Quality Assurance (QA) Team: Ensures that the process follows GMP standards, reviews the documentation, and verifies compliance with regulatory guidelines.

4. Accountability

The Capsule Manufacturing Supervisor is accountable for ensuring the mixing and blending process is carried out according to this SOP. The QA Manager is responsible for ensuring that all quality checks and documentation are completed and compliant with regulatory standards.

5. Procedure

5.1 Selection of Raw Materials

Before starting the mixing and blending process, ensure the following steps are taken:

API Selection
1. Ensure that the active pharmaceutical ingredient (API) is sourced from an approved supplier and is of the correct quality and batch for use in the formulation.
2. Verify that the API meets the required specifications for potency, purity, and other physical characteristics.
Excipient Selection
1. Select excipients based on the formulation requirements, such as binders, fillers, disintegrants, lubricants, and colorants.
2. Ensure excipients are compatible with the API and comply with quality standards.
Weighing of Ingredients
1. Weigh the API and excipients according to the formulation specifications. Use a calibrated balance to ensure accuracy in measurement.
2. Document the batch number and weight of each ingredient for traceability.

5.2 Mixing and Blending Process

The following steps should be followed during the mixing and blending process:

Preparing Equipment
1. Ensure that all mixing equipment, such as blenders or ribbon blenders, is clean and properly calibrated before use.
2. Verify that the equipment is free from any contaminants or residues from previous batches.
Initial Blending
1. Begin by blending the excipients together in the designated mixing equipment. This ensures that the excipients are thoroughly combined before adding the API.
2. Blend for the specified time to achieve a uniform mixture of excipients.
Adding API
1. Slowly add the API to the blended excipients, ensuring even distribution throughout the excipient mix. Use the appropriate mixing speed and duration to prevent API degradation or loss.
2. Monitor the blending process to ensure that the API is evenly distributed and no lumps or agglomerates are formed.
Secondary Blending
1. Blend the mixture for an additional period to ensure the uniformity of the final blend. Periodically check the consistency of the mixture and adjust blending time if necessary.

5.3 Quality Control Checks

Once the mixing and blending process is complete, perform the following quality control checks:

Homogeneity Test
1. Conduct a sample from the blend and test for homogeneity. The API should be evenly distributed across the excipients. Perform a content uniformity test to check for variation in the API content across different parts of the blend.
Moisture Content Test
1. Test the moisture content of the blend to ensure it is within the acceptable range. Excess moisture may affect the flowability of the blend and cause caking or difficulty in capsule filling.
Particle Size Distribution
1. Check the particle size distribution of the blend, especially if fine powders or granules are used. Ensure that the blend has the desired flowability and can be effectively encapsulated.

5.4 Documentation and Record-Keeping

Ensure proper documentation of the entire mixing and blending process:

Batch Records
1. Document the complete batch record for each mixing and blending run, including details of the ingredients, equipment used, mixing time, and any observations made during the process.
Test Results
1. Record the results of all quality control tests performed, including homogeneity, moisture content, and particle size distribution.
Deviation Reports
1. If any deviations occur during the blending process, document them in a deviation report and provide details on the corrective actions taken.

5.5 Storage of Blended Materials

If the blend is not used immediately for capsule filling, store it under appropriate conditions:

Container and Storage
1. Store the blended material in clean, airtight containers to prevent contamination and moisture uptake.
2. Label the containers with the batch number, date of blending, and storage conditions.
Temperature Control
1. Store the blended material in a controlled environment, maintaining a temperature range of 20°C to 25°C. If necessary, store in a climate-controlled room to maintain blend quality.

6. Abbreviations

SOP: Standard Operating Procedure
API: Active Pharmaceutical Ingredient
GMP: Good Manufacturing Practice
QC: Quality Control
QA: Quality Assurance

7. Documents

Mixing and Blending Batch Record (Annexure-1)
Quality Control Test Report (Annexure-2)
Deviation Report (Annexure-3)

8. References

USP <601> – Capsules
FDA Guidelines for Pharmaceutical Manufacturing
International Conference on Harmonization (ICH) Guidelines for Pharmaceutical Product Development

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 and Blending Batch Record

Batch ID	API	Excipients	Weighed Amount	Blending Time	Remarks
Batch 001	Vitamin C	Magnesium Stearate, Lactose	100 g	20 minutes	No deviation

Annexure-2: Quality Control Test Report

Test Type	Result	Specification	Remarks
Homogeneity	Pass	Uniform distribution	Meets standards

Annexure-3: Deviation Report

Deviation ID	Description	Corrective Action	Action Taken By
DR-001	Excess moisture in blend	Drying blend for 30 minutes	Manufacturing Supervisor

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	Added deviation management	Standardization	QA Head