Capsule: SOP for Selection of Capsule Size for Formulations – V 2.0

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Capsule: SOP for Selection of Capsule Size for Formulations – V 2.0

Standard Operating Procedure for Selection of Capsule Size for Formulations

Department Capsule Manufacturing
SOP No. SOP/CM/039/2025
Supersedes SOP/CM/039/2022
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 the appropriate capsule size for different formulations. The goal is to ensure that the selected capsule size accommodates the required dose, ensuring both the stability and ease of administration of the final product.

2. Scope

This SOP applies to the selection of capsule sizes during the development and manufacturing of hard gelatin capsules. The size selection process takes into account the weight and volume of the fill material, as well as regulatory requirements.

3. Responsibilities

  • Formulation Development Team: Responsible for providing information regarding the fill material’s properties, including density and required dose, to ensure the correct capsule size is selected.
  • Manufacturing Team: Responsible for producing the capsules according to the selected size and ensuring uniformity in capsule weight and content.
  • Quality Control (QC) Team: Responsible for verifying that the selected capsule size meets the necessary specifications for weight, volume, and other quality attributes.
  • Quality Assurance (QA) Team: Ensures that the size selection process adheres to GMP and regulatory requirements, and reviews the records to confirm compliance.
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4. Accountability

The Capsule Manufacturing Supervisor is accountable for overseeing the selection process and ensuring that the selected capsule size is suitable for the formulation. The QA Manager is responsible for reviewing the process and ensuring compliance with regulatory standards.

5. Procedure

5.1 Initial Considerations for Capsule Size Selection

Before selecting a capsule size, the following factors should be considered:

  1. Fill Material Properties

    1. Determine the density, flowability, and compressibility of the fill material (API, excipients, or granules).
    2. Ensure that the material can be evenly and efficiently encapsulated without causing issues such as clumping or uneven fill distribution.
  2. Required Dose

    1. Consider the dose to be administered. Larger doses may require larger capsule sizes to accommodate the amount of active pharmaceutical ingredient (API) and excipients.
  3. Desired Release Profile

    1. Consider the type of release profile (e.g., immediate, controlled, extended-release) as it may affect the formulation and capsule size selection.

5.2 Capsule Size Chart

The capsule size chart below provides general guidelines for selecting the appropriate size based on the volume and dose requirements:

Capsule Size Approximate Fill Volume (ml) Typical Fill Weight (mg) Recommended Use
Size 000 1.37 900 mg Large doses, typically for powders or granules
Size 00 1.23 600 mg Common for large dose formulations
Size 0 0.91 400 mg Common for moderate dose formulations
Size 1 0.68 300 mg Moderate to small dose formulations
Size 2 0.37 200 mg Small dose formulations, used for pediatric doses
Size 3 0.30 150 mg Small doses, typically for children or elderly patients
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5.3 Calculating the Appropriate Capsule Size

To calculate the appropriate capsule size for a given formulation, follow these steps:

  1. Determine the Dose per Capsule

    1. Calculate the total dose required for a single capsule. This includes both the API and excipients.
  2. Calculate the Volume of the Fill Material

    1. Determine the volume of the fill material by using its bulk density. The formula is:
    2. Volume = Mass / Density
    3. Ensure the calculated volume fits within the target capsule size based on the volume chart.
  3. Select the Capsule Size

    1. Select the smallest capsule size that can accommodate the required dose and volume of the fill material, while ensuring optimal encapsulation efficiency and ease of swallowing.

5.4 Adjustments for Difficult Fill Materials

If the fill material is difficult to encapsulate (e.g., it has poor flowability or compressibility), consider the following adjustments:

  1. Use of Excipient Modifications

    1. Modify the excipient blend to improve flowability and compressibility, such as adding glidants or binders.
  2. Smaller Fill Quantities

    1. If the dose is too high for the selected capsule size, consider splitting the dose into two smaller capsules or adjusting the formulation.
  3. Capsule Type

    1. If the standard hard gelatin capsule is unsuitable, consider using alternative capsule types, such as soft gelatin capsules or liquid-filled capsules, to accommodate challenging formulations.

5.5 Documentation and Record-Keeping

Document all capsule size selection processes and decisions as follows:

  1. Capsule Size Selection Report

    1. Document the rationale behind the selected capsule size, including the calculation of volume and dose, and any adjustments made during the process.
  2. Batch Records

    1. Ensure that the selected capsule size is recorded in the batch records for reference during production and quality control.
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6. Abbreviations

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

7. Documents

  1. Capsule Size Selection Report Template (Annexure-1)
  2. Capsule Size Chart (Annexure-2)

8. References

  • USP <711> – Dissolution Testing
  • FDA Guidance for Industry: Stability Testing of Drug Products
  • International Conference on Harmonization (ICH) Guidelines for Pharmaceutical 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: Capsule Size Selection Report Template

Material Capsule Size Required Volume Calculated Dose Reason for Size Selection
API A Size 0 1.2 ml 300 mg Selected for optimal dose delivery and efficient encapsulation

Annexure-2: Capsule Size Chart

Capsule Size Volume (ml) Fill Weight (mg)
Size 000 1.37 900 mg
Size 00 1.23 600 mg

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 capsule size chart Standardization QA Head
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