Capsule: SOP for Conducting Solubility Studies for Soft Gelatin Capsules – V 2.0

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Capsule: SOP for Conducting Solubility Studies for Soft Gelatin Capsules – V 2.0

Standard Operating Procedure for Conducting Solubility Studies for Soft Gelatin Capsules

Department Capsule Manufacturing
SOP No. SOP/CM/025/2025
Supersedes SOP/CM/025/2022
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 conducting solubility studies for soft gelatin capsules to assess the dissolution behavior and bioavailability of the encapsulated active pharmaceutical ingredient (API).

2. Scope

This SOP applies to the solubility studies conducted on soft gelatin capsules, including the evaluation of solubility in various solvents and conditions to ensure the effective release of the API from the capsule shell.

3. Responsibilities

  • Formulation Development Team: Responsible for conducting the solubility studies, analyzing results, and optimizing capsule formulations based on the findings.
  • Quality Control (QC) Team: Ensures that the solubility testing procedures meet required quality standards and regulatory requirements.
  • Quality Assurance (QA) Team: Oversees compliance with this SOP and ensures proper documentation and review of solubility testing results.
  • Regulatory Affairs: Ensures that solubility studies meet regulatory guidelines and are aligned with the submission requirements for approval.

4. Accountability

The Formulation Development Supervisor is accountable for ensuring the proper conduct of solubility studies, while the QA Manager ensures compliance with the SOP and regulatory requirements.

5. Procedure

5.1 Selection of Solvents for Solubility Testing

Choose appropriate solvents to evaluate the solubility of the API in the soft gelatin capsules:

  1. Solvent Selection Criteria

    1. Choose solvents based on the solubility profile of the API, ensuring that they mimic physiological conditions (e.g., gastric pH, intestinal pH) if necessary.
    2. Common solvents may include water, simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and other biorelevant solvents depending on the formulation’s release profile.
  2. Solvent Preparation

    1. Prepare the selected solvents according to the specified concentrations and pH values required for the study.
    2. Ensure that all solvents are freshly prepared and filtered, if necessary, to eliminate any particulate matter that could interfere with testing.
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5.2 Conducting Solubility Testing

Perform the solubility testing to determine the ability of the API to dissolve in the chosen solvent:

  1. Test Method Selection

    1. Choose an appropriate testing method for solubility based on the characteristics of the API and the intended release mechanism (e.g., equilibrium solubility, time-dependent solubility).
    2. Ensure that the testing method simulates the in vivo conditions as closely as possible for accurate predictions of API bioavailability.
  2. Test Procedure

    1. Weigh a specified amount of the capsule formulation containing the API, and place it into the solvent for solubility testing.
    2. Stir or shake the solution at a controlled temperature to facilitate the dissolution process (usually at 37°C for physiological relevance).
    3. At regular intervals, sample the solution to measure the concentration of the dissolved API using an appropriate analytical method (e.g., UV-Vis, HPLC).
  3. Observation and Documentation

    1. Observe the dissolution process for any changes in appearance, such as incomplete dissolution, precipitate formation, or gelation.
    2. Document the solubility data, including time intervals, API concentrations, and any changes in the appearance of the solution.
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5.3 Analyzing Solubility Data

Evaluate the solubility data to determine the release profile of the API from the soft gelatin capsules:

  1. Solubility Profile Analysis

    1. Plot the concentration of the dissolved API against time to obtain a dissolution curve.
    2. Determine the rate of dissolution and calculate the percentage of API released over the test period.
  2. Interpretation of Results

    1. Compare the solubility data with the desired release profile (e.g., immediate release, controlled release) to assess the capsule formulation’s suitability.
    2. Ensure that the solubility of the API meets the required standards for bioavailability and efficacy.

5.4 Stability Testing of Solubility Results

Conduct stability testing to assess the long-term performance of the capsule formulation:

  1. Accelerated Stability Testing

    1. Subject the capsule formulations to accelerated stability conditions, such as elevated temperature and humidity, to predict their shelf life.
    2. Monitor any changes in the solubility profile and API degradation under these conditions.
  2. Long-Term Stability Testing

    1. Conduct long-term stability testing under normal storage conditions to confirm the solubility and stability of the API over time.
    2. Evaluate whether the capsule retains its solubility and dissolution characteristics throughout its shelf life.

5.5 Documentation and Record-Keeping

Ensure that all solubility testing and analysis are properly documented:

  1. Test Records

    1. Document all details of the solubility studies, including solvents used, test conditions, sampling intervals, and analytical methods employed.
    2. Ensure that the solubility data is accurately recorded and reviewed by the formulation development and QA teams.
  2. Report Preparation

    1. Prepare a comprehensive report that summarizes the solubility testing process, results, and any necessary conclusions or adjustments to the formulation.
    2. Include recommendations for the next steps based on the solubility findings, including formulation optimization or further testing if required.
  3. Record Retention

    1. Ensure that all records related to solubility testing are securely stored for future reference and regulatory compliance.
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6. Abbreviations

  • SOP: Standard Operating Procedure
  • API: Active Pharmaceutical Ingredient
  • HPLC: High-Performance Liquid Chromatography
  • UV-Vis: Ultraviolet-Visible Spectroscopy
  • SGF: Simulated Gastric Fluid
  • SIF: Simulated Intestinal Fluid
  • QC: Quality Control
  • QA: Quality Assurance

7. Documents

  1. Solubility Test Report (Annexure-1)
  2. Stability Test Data (Annexure-2)
  3. API Dissolution Profile (Annexure-3)

8. References

  • USP <711> – Dissolution Testing
  • ICH Q1A (R2) – Stability Testing of New Drug Substances and Products
  • FDA Guidance for Industry: Dissolution Testing

9. SOP Version

Version: 2.0

10. Approval Section

Prepared By Checked By Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Solubility Test Report

Date API Solvent Test Method Solubility
03/02/2025 API-123 SGF UV-Vis 0.5 mg/mL

Annexure-2: Stability Test Data

Date Test Type Result Action Taken
04/02/2025 Accelerated Stability No degradation Proceed with formulation optimization

Annexure-3: API Dissolution Profile

Date Test Type Release Rate Outcome
05/02/2025 Dissolution Test 85% in 30 minutes 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 solubility testing procedures Standardization and clarity QA Head
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