Standard Operating Procedure for Preparing Liquids for Soft Gelatin Capsules

Department	Capsule Manufacturing
SOP No.	SOP/CM/053/2025
Supersedes	SOP/CM/053/2022
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 provide a standard method for preparing liquid formulations for soft gelatin capsules. The process involves preparing active pharmaceutical ingredients (APIs) and excipients in liquid form, ensuring uniformity and stability before encapsulation.

2. Scope

This SOP applies to the preparation of liquid formulations for soft gelatin capsules, including the selection of raw materials, preparation of the liquid mixture, and ensuring that the final product meets the required specifications for filling into soft gelatin capsules.

3. Responsibilities

• Formulation Development Team: Responsible for designing the liquid formulation and ensuring compatibility between the active ingredients and excipients.
• Manufacturing Team: Responsible for preparing the liquid formulation in compliance with this SOP and ensuring all equipment is properly set up and maintained.
• Quality Control (QC) Team: Responsible for testing the liquid formulation to ensure it meets required specifications such as viscosity, stability, and homogeneity.
• Quality Assurance (QA) Team: Ensures that the preparation process follows GMP and regulatory guidelines and reviews all relevant documentation.

4. Accountability

The Capsule Manufacturing Supervisor is accountable for ensuring that the liquid preparation process follows this SOP. The QA Manager is responsible for reviewing and verifying that the process complies with GMP and regulatory standards.

5. Procedure

5.1 Selection of Raw Materials

The selection of raw materials is crucial to ensure that the liquid formulation is stable, effective, and safe for encapsulation:

1. Active Ingredients
   1. Select the active pharmaceutical ingredients (APIs) based on their solubility, stability, and intended therapeutic effect.
   2. Ensure that the APIs meet the required specifications for purity, strength, and safety.
2. Excipients
   1. Select appropriate excipients such as solvents, preservatives, stabilizers, and surfactants to support the formulation and improve the solubility and stability of the API.
   2. Ensure excipients are compatible with the API and do not interfere with the bioavailability or therapeutic effect.
3. Solvent Selection
   1. Choose a suitable solvent (e.g., water, ethanol, propylene glycol) to dissolve or suspend the API.
   2. Ensure the solvent is safe, compatible with other ingredients, and appropriate for the formulation.

5.2 Preparation of Liquid Formulation

Follow these steps to prepare the liquid formulation:

1. Weighing of Ingredients
   1. Weigh the required amount of API and excipients using a calibrated balance. Ensure accuracy in the weighing process to maintain formulation consistency.
2. Dissolving the API
   1. Slowly add the API to the solvent while stirring continuously. If necessary, apply gentle heat to facilitate dissolution. Do not exceed the recommended temperature to avoid degrading the API.
   2. Ensure the API is completely dissolved before proceeding to the next step.
3. Incorporating Excipients
   1. Once the API is dissolved, add the excipients such as stabilizers, plasticizers, and preservatives, ensuring each is fully incorporated into the solution.
   2. Use a mechanical stirrer or homogenizer to mix the excipients thoroughly and ensure uniformity in the solution.
4. Adjusting the Viscosity
   1. Check the viscosity of the liquid formulation using a viscometer. If necessary, adjust the viscosity by adding more solvent or thickeners to achieve the desired consistency for capsule filling.
5. Filtration (Optional)
   1. If the solution is not clear, filter it using an appropriate filtration system to remove any particles or impurities.

5.3 Quality Control Checks

After preparing the liquid formulation, perform the following quality control checks:

1. Homogeneity Test
   1. Take samples from different parts of the prepared liquid and test for uniform distribution of the API. Ensure the solution is homogeneous and does not exhibit any separation over time.
2. Viscosity Test
   1. Test the viscosity of the liquid formulation to ensure it is within the acceptable range for soft gelatin capsule filling. The viscosity should be suitable for the intended encapsulation process.
3. pH Test
   1. Measure the pH of the liquid formulation to ensure it is within the desired range (typically between 4 and 7) to avoid issues with stability or encapsulation.
4. Stability Test
   1. Conduct stability tests to ensure the formulation remains stable under the intended storage conditions, including temperature and humidity over the required shelf life.

5.4 Storage of Liquid Formulation

After the liquid formulation is prepared, store it under the appropriate conditions:

1. Storage Temperature
   1. Store the liquid formulation in a cool, dry place. The recommended temperature is typically between 20°C and 25°C, depending on the nature of the formulation.
2. Container and Sealing
   1. Store the liquid in airtight, clean, and sterile containers to prevent contamination and evaporation. Label the containers with batch numbers and preparation dates for traceability.
3. Use Within Specified Timeframe
   1. Use the liquid formulation within the recommended timeframe, usually within 24 to 48 hours, to ensure its effectiveness and prevent degradation.

5.5 Documentation and Record-Keeping

Ensure proper documentation for the liquid preparation process:

1. Batch Records
   1. Document all details of the liquid formulation process, including the recipe, the amounts of each ingredient used, the preparation date, and any deviations or changes made during the process.
2. Quality Control Records
   1. Maintain records of all quality control tests, including viscosity, pH, stability, and homogeneity tests. Document the results and compare them with the required specifications.
3. Deviation Reports
   1. If deviations occur during the preparation process, document them in a deviation report and outline the corrective actions taken to resolve the issues.

6. Abbreviations

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

7. Documents

1. Liquid Formulation Batch Record (Annexure-1)
2. Quality Control Testing Report (Annexure-2)
3. Deviation Report (Annexure-3)

8. References

• USP <2040> – Soft Gelatin Capsules
• FDA Guidelines for Pharmaceutical Manufacturing
• International Conference on Harmonization (ICH) Guidelines for Pharmaceutical Product 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: Liquid Formulation Batch Record

Batch ID	API	Excipients	Solvent	Preparation Date
Batch 001	Vitamin E	Glycerin, Sorbitol	Water	01/02/2025

Annexure-2: Quality Control Testing Report

Test Type	Result	Specification	Remarks
Viscosity	350 cps	300-400 cps	Meets standards

Annexure-3: Deviation Report

Deviation ID	Description	Corrective Action	Action Taken By
DR-001	Excess viscosity in formulation	Added more solvent to reduce viscosity	Manufacturing Supervisor

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 testing methods	Standardization	QA Head