Capsule: SOP for Encapsulation of Liquid APIs in Soft Gelatin Capsules – V 2.0

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Capsule: SOP for Encapsulation of Liquid APIs in Soft Gelatin Capsules – V 2.0

Standard Operating Procedure for Encapsulation of Liquid APIs in Soft Gelatin Capsules

Department Capsule Manufacturing
SOP No. SOP/CM/075/2025
Supersedes SOP/CM/075/2022
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 a standard procedure for the encapsulation of liquid active pharmaceutical ingredients (APIs) in soft gelatin capsules. The goal is to ensure the accurate filling of capsules with liquid APIs while maintaining consistency, quality, and compliance with regulatory requirements.

2. Scope

This SOP applies to the encapsulation of liquid APIs into soft gelatin capsules. It includes the preparation of liquid formulations, encapsulation process, quality control measures, and documentation associated with the production of soft gelatin capsules containing liquid APIs.

3. Responsibilities

  • Manufacturing Team: Responsible for carrying out the encapsulation of liquid APIs according to this SOP. They must ensure the process is performed accurately and consistently during each batch.
  • Quality Control (QC) Team: Responsible for testing the encapsulated capsules for API content uniformity, weight uniformity, and integrity. Ensures the liquid encapsulation process meets the defined specifications.
  • Quality Assurance (QA) Team: Ensures that the encapsulation process complies with regulatory guidelines and internal quality standards. Reviews records and verifies compliance with this SOP.
  • Formulation Team: Provides the liquid API formulation and ensures that it is stable and suitable for encapsulation.

4. Accountability

The Capsule Manufacturing Supervisor is accountable for ensuring that the liquid encapsulation process is performed correctly and in accordance with this SOP. The QA Manager is responsible for ensuring that the process is validated, and that quality standards are met during production.

5. Procedure

5.1 Preparation of Liquid API Formulation

Before encapsulation, ensure the following preparations are completed:

  1. Verify Raw Materials

    1. Ensure that all raw materials, including APIs, excipients, and solvents, are approved by the QC department and meet the required specifications. Check expiration dates and ensure proper storage of the materials.
  2. Preparation of Liquid Formulation

    1. Prepare the liquid formulation according to the approved batch formula. Ensure the correct proportion of API and excipients. Use a suitable solvent if required to dissolve or disperse the API.
    2. Ensure the formulation is mixed thoroughly to achieve homogeneity. The liquid should be clear, free from particulate matter, and within the required viscosity range.
  3. Viscosity Control

    1. Check the viscosity of the liquid formulation to ensure it is within the specified range for soft gelatin capsule filling. Use a viscometer to measure the viscosity.
  4. Temperature Control

    1. Ensure the liquid formulation is at the appropriate temperature for encapsulation. Monitor the temperature using a thermometer to prevent degradation of the API or excipients.
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5.2 Encapsulation of Liquid API into Soft Gelatin Capsules

Follow these steps for the encapsulation process:

  1. Capsule Preparation

    1. Select the appropriate size and type of soft gelatin capsule for the liquid fill. Ensure that the capsules are free from any defects, such as cracks or holes, before starting the filling process.
    2. Ensure the capsule filling equipment is clean and calibrated. The capsule machine should be capable of accurately filling liquid into soft capsules.
  2. Filling Process

    1. Load the liquid formulation into the capsule filling machine. Adjust the machine settings, such as fill volume and speed, to ensure accurate dosing of the liquid API into each capsule.
    2. Begin the filling process, carefully monitoring the equipment to ensure that the liquid is dispensed accurately into each capsule. The capsules should be filled to the specified weight or volume as per the formulation requirements.
  3. Sealing the Capsules

    1. After the capsules are filled, ensure that the capsules are properly sealed. Use a sealing method such as banding, soft-heat sealing, or other suitable techniques to prevent leakage of the liquid.
    2. Inspect the capsules for any signs of leakage, deformation, or improper sealing. Segregate any defective capsules for further action or rework.
  4. Post-Encapsulation Inspection

    1. Inspect the filled and sealed soft gelatin capsules visually for any irregularities, including leakage, deformation, or improper sealing. Ensure that the capsules meet all appearance specifications.
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5.3 Quality Control Testing

After encapsulation, perform the following quality control tests:

  1. Content Uniformity

    1. Test the content uniformity of the capsules by sampling and analyzing a representative number of capsules. Ensure that each capsule contains the correct amount of API as per the approved formulation.
  2. Capsule Weight Uniformity

    1. Weigh a sample of capsules and check for uniformity. The weight of each capsule should be within the acceptable range specified for the batch.
  3. Dissolution Test

    1. Perform a dissolution test on a sample of capsules to verify the release profile of the liquid API. Ensure that the dissolution rate is consistent with the required release characteristics.
  4. Visual Inspection

    1. Perform a final visual inspection to ensure that the capsules meet all physical requirements, including size, shape, and appearance. Any defective capsules should be segregated for rework or disposal.

5.4 Post-Encapsulation Actions

After the encapsulation and testing, perform the following actions:

  1. Segregation of Defective Capsules

    1. Immediately segregate any defective capsules identified during the quality control checks. Record the defects and determine whether the capsules can be reworked or should be discarded.
  2. Documentation

    1. Document all details of the encapsulation process, including batch number, formulation details, machine settings, weight and content uniformity results, dissolution results, and any deviations or corrective actions taken during the process.
    2. Ensure that all documents are signed off and stored according to the company’s record-keeping policy.
  3. Transfer to Packaging

    1. Once all quality control tests have been completed and capsules have passed inspection, transfer the capsules to the packaging area. Ensure that the capsules are stored under appropriate conditions to maintain their integrity before packaging.

5.5 Equipment Cleaning and Maintenance

After the encapsulation process, clean and maintain the equipment:

  1. Cleaning

    1. Clean all equipment used in the encapsulation process, including the capsule filling machine, sealing equipment, and any other tools, to remove any residual materials.
    2. Use approved cleaning agents and follow the manufacturer’s cleaning instructions to avoid contamination of the next batch.
  2. Inspection and Maintenance

    1. Inspect the equipment for wear and tear. Ensure that all components are functioning properly and are free from any material build-up that could affect future batches.
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6. Abbreviations

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

7. Documents

  1. Batch Production Record (BPR) (Annexure-1)
  2. Deviation Report (Annexure-2)
  3. Inspection and Testing Log (Annexure-3)
  4. Equipment Maintenance Log (Annexure-4)

8. References

  • USP <1163> – Pharmaceutical Dosage Forms: Capsules
  • FDA Guidelines for Capsule Manufacturing
  • International Conference on Harmonization (ICH) Guidelines for Pharmaceutical Manufacturing

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 Production Record (BPR)

Batch ID Encapsulation Date Liquid API Formulation Encapsulation Parameters Operator Name
Batch 001 01/02/2025 Liquid API Blend Speed: 80 rpm, Fill Volume: 0.5 mL John Doe

Annexure-2: Deviation Report

Deviation ID Description Corrective Action Taken Operator Name
DEV-001 Capsules overfilled Adjusted capsule filling settings John Doe

Annexure-3: Inspection and Testing Log

Batch ID Test Type Result Operator Name
Batch 001 Weight Uniformity Pass John Doe
Batch 001 Content Uniformity Pass Jane Smith

Annexure-4: Equipment Maintenance Log

Equipment ID Maintenance Date Tasks Performed Technician Name
Filling Machine 1 01/02/2025 Calibrated and cleaned 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 encapsulation process Standardization QA Head
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