Capsule: SOP for Designing Extended-Release Capsule Formulations – V 2.0

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Capsule: SOP for Designing Extended-Release Capsule Formulations – V 2.0

Standard Operating Procedure for Designing Extended-Release Capsule Formulations

Department Capsule Manufacturing
SOP No. SOP/CM/043/2025
Supersedes SOP/CM/043/2022
Page No. Page 1 of 7
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 designing extended-release (ER) capsule formulations. The aim is to develop capsules that provide a controlled release of the active pharmaceutical ingredient (API) over an extended period, ensuring that the drug is released gradually and consistently for optimal therapeutic effects.

2. Scope

This SOP applies to the design and development of extended-release capsule formulations in pharmaceutical manufacturing. It includes the selection of excipients, design of the release profile, and optimization of the formulation process.

3. Responsibilities

  • Formulation Development Team: Responsible for designing the extended-release formulation, selecting excipients, and conducting initial trials to achieve the desired release profile.
  • Manufacturing Team: Responsible for producing the extended-release capsules according to the formulated design and maintaining equipment during the process.
  • Quality Control (QC) Team: Responsible for testing the extended-release capsules, including conducting dissolution tests and verifying that the capsules meet the required release profile.
  • Quality Assurance (QA) Team: Ensures that the design and development process adheres to GMP standards and regulatory requirements.

4. Accountability

The Capsule Manufacturing Supervisor is accountable for ensuring that the extended-release capsule formulation is developed and produced as per this SOP. The QA Manager is responsible for ensuring that the formulation complies with regulatory guidelines and quality standards.

5. Procedure

5.1 Formulation Design for Extended-Release Capsules

Before starting the formulation process, consider the following steps:

  1. Define Release Profile

    1. Determine the desired release profile for the API, which may include immediate release, delayed release, or sustained release characteristics. For extended-release capsules, aim for a gradual release over a specified period (e.g., 12 or 24 hours).
  2. Selection of Excipients

    1. Select excipients that help in controlling the release rate of the API. Common excipients include hydrophilic polymers (e.g., HPMC), lipophilic agents (e.g., beeswax), or matrix systems that facilitate sustained release.
    2. Ensure the excipients are compatible with the active ingredient and do not affect its stability, bioavailability, or release profile.
  3. Consideration of API Properties

    1. Assess the solubility and dissolution characteristics of the API. The solubility of the drug can influence the selection of release-modifying excipients.
    2. If the API has poor solubility, consider using solubility enhancers or modifying the formulation to enhance its dissolution rate.
  4. Coating Material Selection

    1. Choose an appropriate coating material if required, such as enteric coatings or sustained-release coatings, depending on the desired release profile.
    2. The coating should not interfere with the drug’s absorption but rather control the release over time.
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5.2 Process Design and Optimization

Optimize the process to ensure uniformity and stability in the extended-release formulation:

  1. Granulation and Matrix Formation

    1. Formulate the extended-release matrix by mixing the API with excipients, followed by granulation to ensure uniform distribution of the API in the formulation.
    2. Optimize the granulation process by adjusting binder concentration, granulation time, and drying conditions to achieve the desired consistency and release rate.
  2. Encapsulation

    1. Encapsulate the formulated mixture into hard gelatin capsules or soft gel capsules, depending on the intended release mechanism and product characteristics.
    2. Ensure uniform filling of capsules to maintain consistent dosage and release profile across all units.
  3. Coating (if applicable)

    1. If coating is required, apply an extended-release coating to the capsule surface to regulate the release rate. Use fluidized bed coating or similar techniques to achieve uniform coating thickness.
    2. Monitor the drying process to ensure the integrity of the coating and prevent premature release or material degradation.
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5.3 Testing Extended-Release Capsules

After the encapsulation process, perform the following tests to ensure the capsules meet the desired extended-release specifications:

  1. Dissolution Testing

    1. Conduct dissolution testing in accordance with USP or other applicable pharmacopeial standards. Perform tests at various time points to verify that the drug is released at the desired rate over time.
    2. Ensure that the dissolution profile of the capsule matches the targeted release profile (e.g., a controlled release over 12-24 hours).
  2. Uniformity of Dosage Units

    1. Ensure that each capsule contains the correct amount of active ingredient and that the fill weight is consistent across all units.
  3. Stability Testing

    1. Conduct stability studies to assess the extended-release formulation’s performance under long-term storage conditions (e.g., temperature, humidity) and to ensure that the release profile remains consistent over time.

5.4 Adjustments Based on Testing Results

If the extended-release capsules do not meet the desired specifications, make the following adjustments:

  1. Adjust Excipients

    1. If the release rate is too fast or too slow, modify the excipient composition, such as increasing the concentration of hydrophilic polymers for slower release or using a different matrix material.
  2. Modify Process Parameters

    1. Adjust process parameters such as granulation time, coating thickness, or drying conditions to optimize the release rate and ensure uniformity.
  3. Reformulate if Necessary

    1. If significant issues arise, consider reformulating the capsule, such as changing the API’s form (e.g., salt form) or altering the encapsulation or coating process.

5.5 Documentation and Record-Keeping

Document all steps and decisions made during the formulation development and manufacturing process:

  1. Formulation Records

    1. Document all materials used in the formulation, including the type and quantity of excipients, API, and any additives.
  2. Batch Records

    1. Record all batch details, including process parameters, equipment settings, and adjustments made during the process.
  3. Testing Records

    1. Record all results from dissolution, dosage uniformity, and stability testing, ensuring that the data is accurate and traceable.
  4. Trial Reports

    1. Prepare a detailed trial report summarizing the results of the development trials, including any modifications made to the formulation or process.
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6. Abbreviations

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

7. Documents

  1. Extended-Release Capsule Formulation Record (Annexure-1)
  2. Extended-Release Capsule Process Record (Annexure-2)
  3. Extended-Release Capsule Test Results (Annexure-3)

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: Extended-Release Capsule Formulation Record

Material Weight Function
Hydroxypropyl Methylcellulose 200 mg Extended-release control

Annexure-2: Extended-Release Capsule Process Record

Batch ID Process Parameters Coating Time Coating Speed
Batch 001 Speed: 100 rpm 30 minutes 15 rpm

Annexure-3: Extended-Release Capsule Test Results

Test Type Test Result Specification Remarks
Dissolution Pass 90% release in 12 hours Meets dissolution requirements

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 formulation and process parameters Standardization QA Head
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