Standard Operating Procedure for Optimization of Capsule Fill Volume

Department	Capsule Manufacturing
SOP No.	SOP/CM/028/2025
Supersedes	SOP/CM/028/2022
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 establish the procedure for optimizing the fill volume in capsule manufacturing, ensuring accurate and consistent dosage while minimizing material waste and production errors.

2. Scope

This SOP applies to all capsule formulations produced within the manufacturing facility. It covers the processes involved in optimizing capsule fill volume, including equipment calibration, formulation adjustments, and quality control testing.

3. Responsibilities

• Formulation Development Team: Responsible for designing formulations with the correct fill volume and ensuring that the formulation is compatible with the capsule shell and manufacturing process.
• Manufacturing Team: Responsible for performing capsule filling, ensuring accurate volume measurements, and adhering to the prescribed process parameters.
• Quality Control (QC) Team: Responsible for testing the filled capsules to ensure uniformity, content accuracy, and compliance with specified fill volume standards.
• Quality Assurance (QA) Team: Oversees compliance with this SOP, ensuring that the fill volume optimization process meets regulatory and quality standards.

4. Accountability

The Capsule Manufacturing Supervisor is accountable for ensuring that the fill volume is optimized throughout the manufacturing process. The QA Manager is responsible for ensuring that the SOP is followed and that any deviations are documented and addressed.

5. Procedure

5.1 Define Desired Capsule Fill Volume

Establish the required fill volume for each capsule formulation:

1. Capsule Size and API Dose
   1. Determine the appropriate capsule size based on the required dose of the active pharmaceutical ingredient (API) and the selected excipients.
   2. Ensure that the capsule size accommodates the required dose while considering the volume of excipients, fillers, and other formulation components.
2. Formulation Type
   1. Identify the formulation type (e.g., powder blend, granules, pellets) and calculate the appropriate fill volume based on the formulation density and capsule size.

5.2 Adjust Formulation for Optimal Fill Volume

Optimize the formulation to achieve the desired fill volume and ensure proper filling:

1. Excipients Selection
   1. Choose excipients that help achieve the required bulk density for the capsule fill, ensuring the powder blend or granules flow properly into the capsule shell.
   2. Adjust excipient concentrations to achieve the desired fill volume while maintaining the stability and functionality of the API.
2. Granulation and Mixing
   1. If necessary, adjust the granulation process (wet or dry) to improve the uniformity and flowability of the formulation, which aids in achieving an even fill volume during capsule filling.
   2. Ensure that the blend is homogeneous, with no segregation of components, to achieve accurate fill volumes during production.

5.3 Capsule Filling Process

Conduct the capsule filling process using calibrated equipment and optimized parameters:

1. Equipment Calibration
   1. Calibrate filling machines, including automatic capsule filling machines and manual filling equipment, to ensure accuracy in filling volume.
   2. Verify that the equipment is adjusted to the correct fill volume setting, based on the formulation’s characteristics and required capsule weight.
2. Filling Procedure
   1. Ensure the capsule shells are appropriately positioned and aligned on the filling machine.
   2. Load the powder or granules into the filling machine hopper and begin the filling process, carefully monitoring the fill volume for consistency.
   3. Regularly inspect the filled capsules to ensure that the correct fill volume is achieved and that no capsules are overfilled or underfilled.

5.4 Testing and Verification of Fill Volume

Test the filled capsules to ensure consistency and accuracy of the fill volume:

1. Weight Uniformity Test
   1. Weigh a sample of capsules from each batch and calculate the average weight and standard deviation.
   2. Ensure that the weight variation is within the permissible limits specified by regulatory authorities (e.g., USP or EP standards).
2. Content Uniformity Test
   1. Test the content uniformity of a sample of capsules to ensure that the API is distributed uniformly across the batch.
   2. Ensure that each capsule contains the correct amount of API, within the specified range of the label claim.
3. Dissolution Testing
   1. Perform dissolution tests to evaluate the release profile of the API and ensure the capsules dissolve within the desired time frame.
   2. Verify that the capsule fill does not hinder API dissolution and that the release rate meets the desired specifications.

5.5 Adjusting the Fill Volume

If the fill volume is not within the desired range, adjust the formulation or equipment settings as follows:

1. Formulation Adjustments
   1. Adjust the excipient concentrations or switch to a different excipient to improve the powder flowability or bulk density, ensuring the desired fill volume is achieved.
   2. Reformulate the blend to achieve a uniform and consistent density, optimizing the fill volume during the next filling cycle.
2. Equipment Adjustments
   1. Adjust the filling machine settings, such as the fill weight, hopper speed, and tamping pressure, to improve fill volume accuracy.
   2. Calibrate the equipment again if the fill volume discrepancies persist, ensuring that the filling machine is consistently dispensing the correct amount of material.

5.6 Documentation and Record-Keeping

Document all activities related to capsule fill volume optimization:

1. Fill Volume Records
   1. Document the results of the weight uniformity, content uniformity, and dissolution tests, including all calculations and observations.
   2. Ensure that the records are signed off by the relevant personnel, including the formulation development team and QC team.
2. Batch Records
   1. Document the batch production records, including the excipient quantities, API batch, equipment settings, and process parameters used for each production cycle.
   2. Ensure that all records are securely stored for future reference and regulatory compliance purposes.

6. Abbreviations

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

7. Documents

1. Capsule Fill Volume Report (Annexure-1)
2. Batch Production Record (Annexure-2)
3. Quality Control Testing Data (Annexure-3)

8. References

• USP <711> – Dissolution Testing
• ICH Q1A (R2) – Stability Testing of New Drug Substances and Products
• FDA Guidance for Industry: Capsule Filling

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Capsule Fill Volume Report

Date	Batch Number	Capsule Size	Weight Uniformity	Content Uniformity
03/02/2025	Batch-123	Size 1	Pass	Pass

Annexure-2: Batch Production Record

Date	Batch Number	Capsule Shell Type	Filling Equipment
03/02/2025	Batch-123	Gelatin	Filling Machine 1

Annexure-3: Quality Control Testing Data

Date	Test Type	Result	Action Taken
04/02/2025	Weight Uniformity	Pass	Proceed to next phase

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 fill volume optimization procedure	Standardization and clarity	QA Head