Capsule: SOP for Selecting Plasticizers for Soft Gelatin Capsule Shells – V 2.0

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Capsule: SOP for Selecting Plasticizers for Soft Gelatin Capsule Shells – V 2.0

Standard Operating Procedure for Selecting Plasticizers for Soft Gelatin Capsule Shells

Department Capsule Manufacturing
SOP No. SOP/CM/033/2025
Supersedes SOP/CM/033/2022
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 selecting plasticizers for soft gelatin capsule shells, ensuring that the selected plasticizer enhances the flexibility, stability, and overall quality of the capsule shells.

2. Scope

This SOP applies to the selection of plasticizers used in the formulation of soft gelatin capsules. It covers the criteria for plasticizer selection, testing, and evaluation to ensure that the final capsule meets quality, regulatory, and performance requirements.

3. Responsibilities

  • Formulation Development Team: Responsible for identifying the appropriate plasticizer based on formulation requirements, ensuring compatibility with gelatin and other excipients, and testing the physical properties of the resulting capsule shell.
  • Quality Control (QC) Team: Responsible for testing the physical properties of the soft gelatin capsules and ensuring that the selected plasticizer results in a product that meets the required specifications for flexibility, stability, and dissolution.
  • Quality Assurance (QA) Team: Ensures compliance with this SOP, reviews the selection process, and approves the final formulation.
  • Regulatory Affairs: Ensures that the selected plasticizers comply with regulatory guidelines and can be included in the final product for market approval.

4. Accountability

The Formulation Development Supervisor is accountable for selecting the appropriate plasticizer based on the desired capsule shell characteristics. The QC Manager is responsible for testing the final product to ensure that the capsule meets the required physical properties and performance standards.

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5. Procedure

5.1 Criteria for Plasticizer Selection

Define the criteria for selecting a plasticizer for soft gelatin capsule shells:

  1. Compatibility with Gelatin

    1. Ensure that the plasticizer is compatible with gelatin, both chemically and physically, and does not interfere with the dissolution or bioavailability of the capsule contents.
  2. Plasticizer Effectiveness

    1. Select a plasticizer that effectively reduces the brittleness of the gelatin shell and increases its flexibility, making it easier to handle and less prone to cracking during storage and transport.
  3. Regulatory Compliance

    1. Ensure that the selected plasticizer complies with applicable regulations and standards (e.g., FDA, EMA) for use in pharmaceutical dosage forms.
  4. Stability

    1. Choose a plasticizer that does not compromise the long-term stability of the capsule shell, especially under varying temperature and humidity conditions.
  5. Viscosity Control

    1. The selected plasticizer should help maintain the desired viscosity of the gelatin solution during capsule manufacturing.

5.2 Types of Plasticizers

Review the different types of plasticizers that are commonly used in soft gelatin capsule formulations:

  1. Glycerin

    1. Glycerin is a widely used plasticizer for soft gelatin capsules that enhances flexibility without affecting capsule dissolution. It is commonly used for aqueous-based formulations.
  2. Sorbitol

    1. Sorbitol is another common plasticizer that provides similar benefits as glycerin, with the added advantage of being less hygroscopic. It is also widely used for soft gelatin capsule formulations.
  3. Propylene Glycol

    1. Propylene glycol is effective for improving the flexibility and plasticity of gelatin shells, and it is particularly useful in formulations requiring reduced moisture content.
  4. Phthalates

    1. Phthalates, such as dioctyl phthalate (DOP), are used for soft gelatin capsules requiring enhanced flexibility, though they are less commonly used today due to regulatory concerns regarding their safety.
  5. Triacetin

    1. Triacetin is a plasticizer commonly used for soft gelatin capsules that require high plasticity and flexibility while maintaining stability under high humidity conditions.
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5.3 Selection Process

Follow the procedure to select the appropriate plasticizer for soft gelatin capsules:

  1. Formulation Evaluation

    1. Review the formulation’s requirements, including capsule shell strength, dissolution profile, and storage conditions.
    2. Based on the compatibility and desired properties, shortlist potential plasticizers for the formulation.
  2. Plasticizer Testing

    1. Test the shortlisted plasticizers for their impact on the physical properties of gelatin, including viscosity, flexibility, and gel strength.
    2. Prepare gelatin formulations using different plasticizers and perform rheological tests to measure the impact on viscosity and flexibility.
  3. Stability Testing

    1. Test the stability of the gelatin formulations containing different plasticizers under accelerated stability conditions (e.g., high temperature and humidity) to ensure that the formulation will remain stable over time.
  4. Regulatory Review

    1. Ensure that the selected plasticizer complies with relevant regulations (e.g., FDA, EMA) for use in pharmaceutical capsules and that it is included in the approved excipient list for capsule production.

5.4 Documentation and Record-Keeping

Ensure thorough documentation of the plasticizer selection process:

  1. Selection Report

    1. Document the evaluation process, including the criteria for selecting the plasticizer, testing methods, and results from rheological and stability tests.
    2. Ensure that the selection of the plasticizer is justified based on the data gathered during testing and that the final choice is approved by the Formulation Development and QA teams.
  2. Test Results

    1. Document the results of all physical and stability tests on the gelatin formulations, including viscosity, flexibility, and dissolution profiles.
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5.5 Adjustments Based on Plasticizer Performance

If the selected plasticizer does not provide the desired results, adjustments may be required:

  1. Adjusting Plasticizer Concentration

    1. If the gelatin formulation is too rigid or brittle, consider increasing the concentration of the plasticizer or switching to a more effective plasticizer.
  2. Switching Plasticizers

    1. If the selected plasticizer does not meet the desired specifications for flexibility or stability, consider switching to a different plasticizer and repeating the evaluation and testing process.

6. Abbreviations

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

7. Documents

  1. Plasticizer Selection Report (Annexure-1)
  2. Gelatin Formulation Testing Data (Annexure-2)

8. References

  • USP <701> – Gelatin for Pharmaceutical Use
  • FDA Guidance for Industry: Capsule Dosage Forms
  • EMA Guidelines for Excipients in Medicinal Products

9. SOP Version

Version: 2.0

10. Approval Section

Prepared By Checked By Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Plasticizer Selection Report

Date Plasticizer Gelatin Batch Testing Results Action
03/02/2025 Glycerin Batch A Pass Approved for formulation

Annexure-2: Gelatin Formulation Testing Data

Date Test Result Plasticizer
02/02/2025 Viscosity 2000 cP Glycerin

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 plasticizer selection process Standardization QA Head
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