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 outline the procedure for selecting plasticizers for soft gelatin capsule shells to achieve the required flexibility, stability, and performance characteristics for the final product.

2. Scope

This SOP applies to the selection and use of plasticizers in the formulation of soft gelatin capsule shells. It includes the criteria for selecting appropriate plasticizers based on the formulation requirements and product specifications.

3. Responsibilities

  • Formulation Development Team: Responsible for selecting the appropriate plasticizer based on the desired properties of the capsule shell, including flexibility, stability, and dissolution profile.
  • Quality Control (QC) Team: Responsible for testing the plasticized gelatin formulation to ensure it meets the required specifications for capsule production.
  • Quality Assurance (QA) Team: Ensures that the plasticizer selection process follows this SOP and that all relevant documentation is reviewed and approved.
  • Manufacturing Team: Responsible for incorporating the selected plasticizer into the gelatin formulation and ensuring consistency during production.

4. Accountability

The Capsule Manufacturing Supervisor is accountable for ensuring the proper selection and use of plasticizers in soft gelatin capsule formulation. The QC Manager ensures that the selected plasticizers are suitable for the formulation and meet the required standards.

5. Procedure

5.1 Criteria for Selecting Plasticizers

Plasticizers are selected based on the following criteria:

  1. Gelatin Compatibility

    1. The plasticizer must be compatible with the gelatin used for capsule shell formation to avoid separation or instability during production.
    2. Ensure that the plasticizer does not negatively affect the gelatin’s ability to form a smooth, uniform capsule shell.
  2. Flexibility and Plasticity

    1. The selected plasticizer should impart the necessary flexibility to the capsule shell, ensuring that the capsules are easy to handle, fill, and seal during the manufacturing process.
    2. The plasticizer should reduce the brittleness of the gelatin shell, especially in conditions of low humidity.
  3. Stability

    1. The plasticizer should not adversely affect the stability of the capsule, particularly over the shelf life of the product. It should be resistant to oxidation and hydrolysis under typical storage conditions.
  4. Regulatory Compliance

    1. The plasticizer must comply with relevant regulatory guidelines (e.g., FDA, USP, EMA) and be listed as acceptable for pharmaceutical use.
    2. Ensure that the plasticizer is on the approved list of excipients for the intended application.
  5. Toxicity Profile

    1. The plasticizer must have a low toxicity profile and should not pose any risk to the end-user, particularly in the case of chronic exposure or ingestion.
  6. Dissolution Properties

    1. The selected plasticizer should not significantly affect the dissolution of the capsule shell or the API’s release from the capsule. The plasticizer should not slow down the dissolution process.
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5.2 Common Plasticizers for Soft Gelatin Capsules

There are several commonly used plasticizers for soft gelatin capsules, which can be selected based on the formulation and desired properties:

  1. Glycerin (Glycerol)

    1. Glycerin is a widely used plasticizer in soft gelatin capsules. It imparts flexibility and has a long history of safe use in pharmaceutical formulations.
    2. Glycerin is particularly effective in gelatin-based capsule formulations and provides the necessary flexibility while maintaining capsule integrity.
  2. Polyethylene Glycol (PEG)

    1. Polyethylene glycol is commonly used as a plasticizer for gelatin capsules to improve elasticity and reduce brittleness.
    2. PEG is available in various molecular weights, with higher molecular weight PEG providing increased flexibility.
  3. Sorbitol

    1. Sorbitol is another plasticizer used in soft gelatin capsules. It improves the capsule’s flexibility and reduces its tendency to become brittle.
    2. Sorbitol is particularly useful in formulations where a high degree of flexibility is required, especially in low-humidity environments.
  4. Propylene Glycol

    1. Propylene glycol is used as a plasticizer to enhance the flexibility and plasticity of the gelatin shell.
    2. It is particularly effective in formulations requiring a longer shelf-life, as it contributes to the stability of the gelatin shell under varying humidity conditions.
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5.3 Incorporating Plasticizer into the Gelatin Formulation

Once the appropriate plasticizer has been selected, it must be incorporated into the gelatin formulation:

  1. Weighing and Mixing

    1. Weigh the plasticizer according to the formulation specifications (usually 10-30% of the weight of the gelatin).
    2. Incorporate the plasticizer into the gelatin solution before encapsulation, ensuring it is thoroughly mixed to achieve uniform distribution.
  2. Homogeneity

    1. Ensure that the mixture of gelatin and plasticizer is homogeneous by using appropriate mixing equipment (e.g., planetary mixers or high-shear mixers).
    2. Monitor the mixture for any phase separation or inconsistencies, which could affect capsule shell formation.

5.4 Testing and Evaluation

After incorporating the plasticizer into the gelatin formulation, the following tests should be conducted:

  1. Viscosity and Flowability

    1. Test the viscosity of the gelatin mixture after adding the plasticizer to ensure it is within the acceptable range for capsule production.
    2. Evaluate the flowability of the gelatin mixture to ensure smooth filling and encapsulation during production.
  2. Capsule Shell Integrity

    1. Evaluate the final capsule shells for flexibility, strength, and elasticity. Capsules should not crack, break, or exhibit signs of brittleness.
    2. Conduct stress testing to evaluate the ability of the capsules to withstand transportation, handling, and storage conditions without compromising their integrity.
  3. Dissolution Testing

    1. Ensure that the dissolution properties of the capsule shell are not adversely affected by the addition of the plasticizer. The capsule should dissolve within the specified time frame under the prescribed conditions.
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5.5 Documentation and Record-Keeping

All procedures and testing related to the selection and incorporation of plasticizers must be documented:

  1. Plasticizer Selection Records

    1. Document the plasticizer selection process, including the rationale for the choice of plasticizer and any relevant test data (e.g., viscosity, dissolution, flexibility).
    2. Ensure that all records are signed by the responsible personnel and stored securely for future reference and regulatory compliance.
  2. Testing and Evaluation Reports

    1. Document the results of all tests, including viscosity, capsule shell integrity, and dissolution, ensuring that the plasticizer meets the required specifications.

6. Abbreviations

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

7. Documents

  1. Plasticizer Selection Report (Annexure-1)
  2. Capsule Shell Integrity Report (Annexure-2)

8. References

  • USP <701> – Gelatin Capsules
  • FDA Guidance for Industry: Excipients in Pharmaceutical Formulations
  • EMA Guideline on Excipients in the Manufacture of Pharmaceutical 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 Used Viscosity Shell Integrity
02/02/2025 Glycerin 2500 cP Pass

Annexure-2: Capsule Shell Integrity Report

Date Batch Number Flexibility Integrity Test Result
02/02/2025 Batch-001 Pass Pass

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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