standards.

5. Procedure

5.1 Sample Preparation

1. Weigh approximately 50-100 g of granules for bulk density testing, ensuring a homogeneous sample.
2. Transfer the granules into a clean, dry graduated cylinder or container with known volume (typically 100 mL or 250 mL).
3. Ensure there is no moisture or dust contamination in the sample container.

5.2 Performing the Bulk Density Test

1. Tap the graduated cylinder gently on a flat surface or use a tapping apparatus for consistent tapping (e.g., 100 taps) to settle the granules.
2. Record the final volume of the granules after tapping, ensuring it is stable and consistent.
3. Calculate the bulk density using the following formula:
   • Bulk Density (g/mL) = Mass of the sample (g) / Volume of the granules (mL)

5.3 Repeat Testing

1. Repeat the bulk density testing for a minimum of three different samples from the same batch to ensure reproducibility of the results.
2. Ensure that all samples are tested under the same conditions and using the same volume measurement method.

5.4 Data Analysis and Calculation

1. Calculate the average bulk density from the three measurements and report the final value.
2. If any measurement deviates significantly (more than ±5%) from the others, investigate and perform re-testing.

5.5 Acceptance Criteria

1. The bulk density of the granules should fall within the predefined limits based on the formulation’s requirements (e.g., 0.5–1.0 g/mL for most tablet formulations).
2. If the bulk density falls outside the acceptable range, investigate potential causes such as particle size distribution, moisture content, or compaction issues in the granulation process.
3. Document any deviations and corrective actions taken (Annexure-1).

5.6 Documentation and Record-Keeping

1. Record all bulk density test results, including the mass, volume measurements, and final bulk density calculations, 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 weighing logs and any additional testing results, for regulatory compliance and future reference.

5.7 Post-Test Actions

1. Clean the graduated cylinders or containers used for bulk density testing to remove any residual granules or powder.
2. Dispose of used samples, solvents, and reagents according to the company’s waste disposal procedures.
3. Ensure that laboratory instruments are maintained and calibrated according to the instrument SOP.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• g/mL: Grams per Milliliter

7. Documents

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

8. References

• USP <616> – Granulation and Powder Flowability
• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• European Pharmacopoeia (EP) – Specifications for Granule 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: Deviation Report

Deviation Date	Batch Number	Deviation Description	Corrective Action	Responsible Person
15/12/2025	Batch 001	Bulk density outside acceptable range	Adjusted granulation process and re-tested	John Doe

Annexure-2: Batch Record

Batch Number	Sample Weight (g)	Volume (mL)	Bulk Density (g/mL)	Result
Batch 001	100 g	150 mL	0.67 g/mL	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 Acceptance Criteria	Improved granule flowability requirements	QA Head