Standard Operating Procedure for Particle Morphology Analysis in Sustained Release Tablets

Department	Quality Control
SOP No.	SOP/TAB/113/2025
Supersedes	SOP/TAB/113/2022
Page No.	Page 1 of 6
Issue Date	01/03/2026
Effective Date	06/03/2026
Review Date	01/03/2027

1. Purpose

To define the procedure for performing particle morphology analysis of granules and tablets in sustained release formulations, ensuring the uniformity and consistency of particle size, shape, and surface characteristics for optimal performance.

2. Scope

This SOP applies to the analysis of particle morphology in sustained release tablets. The procedure is intended for assessing the particle size, shape, and surface morphology using microscopy techniques, such as Scanning Electron Microscopy (SEM) or Optical Microscopy.

3. Responsibilities

• Quality Control (QC): Responsible for performing particle morphology analysis and ensuring that the results meet the required specifications for sustained release tablet formulations.
• Quality Assurance (QA): Ensures that the analysis is conducted following this SOP and reviews the results to ensure compliance with quality standards and regulatory requirements.
• Laboratory Personnel: Responsible for preparing the samples, operating the microscope or SEM, and recording the results accurately.

4. Accountability

The QC Manager is accountable for ensuring that particle morphology analysis is performed accurately and in compliance with regulatory requirements. The QA Manager is responsible for reviewing and approving the analysis results and ensuring that the formulation meets the product’s specifications.

5. Procedure

5.1 Sample Preparation

1. Obtain a representative sample of the granules or tablets from the batch to be tested.
2. If testing granules, use a suitable amount (e.g., 100 mg) of granules to assess particle morphology.
3. If testing tablets, prepare a small section or crush the tablet to obtain a representative portion for analysis.
4. Ensure that the sample is free from contaminants such as moisture, dust, or foreign particles that could interfere with the analysis.

5.2 Microscopy Technique Selection

1. Choose the appropriate microscopy technique based on the sample and required level of detail. Common techniques include:
   • Optical Microscopy: For visual inspection of general particle shape and size distribution.
   • Scanning Electron Microscopy (SEM): For high-resolution analysis of particle surface morphology, porosity, and surface texture.
2. Ensure that the selected technique is calibrated and ready for use.

5.3 Performing the Particle Morphology Analysis

1. For optical microscopy:
   • Place the prepared sample on a clean microscope slide.
   • Use a suitable magnification (e.g., 10x to 100x) to examine the particle size and shape.
   • Document the observations and photograph representative particles for record-keeping.
2. For SEM:
   • Place the sample on the SEM stage and coat it with a conductive layer (e.g., gold or carbon) if necessary.
   • Set the appropriate voltage and magnification (e.g., 500x to 5000x) based on the analysis requirements.
   • Record the micrographs of the particles, paying attention to surface texture, shape, and size distribution.

5.4 Data Analysis

1. Measure and analyze the particle size, shape, and surface characteristics from the images or micrographs obtained from the microscopy analysis.
2. Calculate the average particle size, particle size distribution, and other relevant morphological parameters (e.g., aspect ratio, circularity) for granules or tablets.
3. Compare the morphology data with the established specifications for the formulation. Ensure that the particles meet the required criteria for sustained release performance (e.g., uniformity in size and surface area).

5.5 Acceptance Criteria

1. The particles should meet predefined specifications for size, shape, and surface morphology. Acceptable criteria may include:
   • Uniformity in particle size distribution (e.g., 90% of particles within ±10% of the mean diameter).
   • Appropriate shape (e.g., spherical or irregular) for optimal flow and compression in tablet manufacturing.
   • Surface characteristics suitable for sustained release, such as sufficient porosity for drug release.
2. If the particle morphology does not meet the required criteria, investigate potential causes and document findings in a deviation report (Annexure-1).
3. Perform corrective actions, such as adjusting the granulation process or modifying the formulation, and re-test as necessary.

5.6 Documentation and Record-Keeping

1. Document all particle morphology analysis results, including images, particle size measurements, and morphological characteristics, in the batch record (Annexure-2).
2. Ensure that all records are signed, dated, and stored according to the company’s record retention policy for future audits and inspections.
3. Maintain raw data, including SEM micrographs, optical microscopy images, and any relevant calculations, for regulatory compliance and future reference.

5.7 Post-Test Actions

1. Clean the microscopy equipment (e.g., SEM, optical microscope) after each use to remove any sample residue and prevent cross-contamination.
2. Dispose of any used samples, reagents, or solvents according to the company’s waste disposal procedures.
3. Ensure that the equipment used for particle morphology analysis is maintained, calibrated, and serviced according to the manufacturer’s guidelines and company SOPs.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• SEM: Scanning Electron Microscopy
• API: Active Pharmaceutical Ingredient

7. Documents

1. Batch Record (Annexure-2)
2. Deviation Report (Annexure-1)

8. References

• USP <711> – Dissolution Testing of Tablets
• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• European Pharmacopoeia (EP) – Specifications for Particle Size Testing and Morphology

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Deviation Report

Deviation Date	Batch Number	Deviation Description	Corrective Action	Responsible Person
15/12/2025	Batch 001	Inconsistent particle size distribution	Adjusted granulation process and re-tested	Jane Smith

Annexure-2: Batch Record

Batch Number	Sample Weight (g)	Particle Size (µm)	Shape (Visual)	Surface Texture (SEM)	Result
Batch 001	100 g	250-500 µm	Irregular	Smooth	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 Testing Conditions	Improved morphology analysis method	QA Head