Standard Operating Procedure for Conducting Rheological Studies on Gelatin

Department	Capsule Manufacturing
SOP No.	SOP/CM/032/2025
Supersedes	SOP/CM/032/2022
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 rheological studies on gelatin to determine its flow properties, which are critical for capsule shell formulation, texture, and performance during manufacturing.

2. Scope

This SOP applies to the rheological testing of gelatin used in capsule shell preparation. It includes the procedures for measuring the viscosity, shear stress, and other rheological properties of gelatin formulations.

3. Responsibilities

• Formulation Development Team: Responsible for preparing the gelatin formulations and defining the required rheological properties for capsule shell production.
• Quality Control (QC) Team: Responsible for conducting rheological tests, ensuring that gelatin meets the required specifications for consistency and performance.
• Quality Assurance (QA) Team: Ensures that the rheological studies comply with this SOP, reviews test results, and approves the formulation for further processing.
• Manufacturing Team: Responsible for ensuring that gelatin formulations with the correct rheological properties are used during capsule production.

4. Accountability

The Capsule Manufacturing Supervisor is accountable for ensuring that rheological studies are conducted as per this SOP and that the gelatin formulation used in capsule production meets the required specifications. The QC Manager is responsible for overseeing the testing and ensuring the data’s accuracy and compliance with specifications.

5. Procedure

5.1 Preparation of Gelatin Samples

Prepare the gelatin formulation samples before conducting the rheological study:

1. Gelatin Preparation
   1. Weigh the appropriate quantity of gelatin powder based on the formulation requirements for the capsule shell.
   2. Dissolve the gelatin in the required amount of water, following the prescribed temperature and mixing conditions.
   3. Ensure that the gelatin is fully dissolved to avoid any inconsistencies in rheological testing.
2. Additional Ingredients
   1. If necessary, add other excipients such as plasticizers, colorants, or preservatives to the gelatin solution as per the formulation specifications.
   2. Mix the ingredients thoroughly to ensure uniformity before testing.

5.2 Rheological Testing Setup

Set up the equipment and test parameters for the rheological study:

1. Equipment Selection
   1. Select an appropriate rheometer (e.g., rotational viscometer or cone-and-plate viscometer) for testing the gelatin’s rheological properties.
   2. Ensure the rheometer is calibrated and in good working condition before use.
2. Test Parameters
   1. Define the shear rate range (e.g., 0.1 to 100 s⁻¹) and temperature (e.g., 25°C) for testing the gelatin’s viscosity.
   2. Set the temperature controller if applicable, to maintain a constant temperature during the study.

5.3 Conducting Rheological Tests

Perform the rheological tests to measure the flow properties of the gelatin formulation:

1. Viscosity Test
   1. Place the gelatin sample into the rheometer and initiate the test, measuring the shear viscosity at various shear rates (e.g., 0.1, 1, 10, 100 s⁻¹).
   2. Record the viscosity readings at each shear rate to determine the flow behavior of the gelatin (e.g., Newtonian, shear-thinning, shear-thickening).
2. Shear Stress Measurement
   1. Measure the shear stress required to achieve a specific shear rate, which is crucial in determining the material’s behavior under different stress conditions.
   2. Monitor the shear stress values and plot them to visualize the gelatin’s yield stress and plastic behavior, if applicable.
3. Thixotropy Test
   1. If applicable, perform a thixotropy test by measuring the recovery of viscosity after shear stress is removed to evaluate the gelatin’s structural recovery.

5.4 Data Analysis and Interpretation

Analyze the rheological data and interpret the results based on the required gelatin properties for capsule shell formation:

1. Flow Behavior
   1. Determine the flow behavior index (n) from the viscosity-shear rate data to assess whether the gelatin exhibits Newtonian, shear-thinning, or shear-thickening behavior.
   2. For capsule shell formation, shear-thinning behavior is typically desired to facilitate smooth filling and molding.
2. Viscosity and Shear Stress
   1. Analyze the viscosity values at different shear rates to determine the gelatin’s suitability for capsule production.
   2. Ensure that the shear stress measurements are within acceptable limits for the chosen encapsulation equipment and processing conditions.
3. Thixotropy Behavior
   1. Evaluate the recovery time and consistency of the gelatin after shear stress is removed. This property is crucial for the stability and handling of the capsule shell material.

5.5 Adjustments Based on Rheological Results

If the rheological properties of the gelatin do not meet the required specifications for capsule shell production, adjustments may be necessary:

1. Formulation Adjustments
   1. If the viscosity is too high or too low, adjust the excipient concentrations (e.g., plasticizer content) to modify the gelatin’s flow properties.
   2. Consider adjusting the gelatin concentration or using different grades of gelatin to achieve the desired rheological behavior.
2. Processing Adjustments
   1. If the gelatin exhibits poor thixotropy, adjust the mixing or temperature conditions to improve its shear-thinning behavior and handling properties.

5.6 Documentation and Record-Keeping

Ensure that all rheological testing is thoroughly documented and reviewed:

1. Test Records
   1. Document all rheological test results, including viscosity, shear stress, and thixotropy data, along with the conditions under which the tests were conducted (e.g., shear rate, temperature).
   2. Ensure that the records are signed by the testing personnel and reviewed by the QC Manager.
2. Report Preparation
   1. Prepare a summary report with an analysis of the rheological properties and their implications for capsule shell formulation.
   2. Ensure that any deviations from the expected results are documented and corrective actions are proposed.

6. Abbreviations

• SOP: Standard Operating Procedure
• QC: Quality Control
• QA: Quality Assurance
• GMP: Good Manufacturing Practice
• API: Active Pharmaceutical Ingredient
• viscosity: Resistance to flow
• shear stress: Force per unit area applied to a material

7. Documents

1. Rheological Test Report (Annexure-1)
2. Batch Record (Annexure-2)

8. References

• USP <601> – Gelatin for Pharmaceutical Use
• FDA Guidance for Industry: Gelatin in Capsule Formulations
• ISO 1101 – Rheological Methods

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Rheological Test Report

Date	Gelatin Batch	Viscosity	Shear Stress	Thixotropy
02/02/2025	Batch A	2000 cP	5 Pa	Pass

Annexure-2: Batch Record

Date	Batch Number	Gelatin Concentration	Temperature
02/02/2025	Batch A	30%	40°C

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 rheological testing procedure	Standardization	QA Head