Standard Operating Procedure for Granule Bulk Density Determination
| Department | Tablet |
|---|---|
| SOP No. | SOP/TAB/028/2025 |
| Supersedes | SOP/TAB/028/2022 |
| Page No. | Page 1 of 6 |
| Issue Date | 28/06/2025 |
| Effective Date | 03/07/2025 |
| Review Date | 28/06/2026 |
1. Purpose
This SOP defines the procedure for determining the bulk density of granules, which is an important parameter for ensuring uniformity in tablet formulations. The bulk density of granules impacts the flowability, compressibility, and final tablet weight, all critical factors in tablet production.
2. Scope
This SOP applies to the determination of bulk density for granules used in tablet manufacturing. It covers the equipment setup, granule sample preparation, and the measurement procedure to accurately determine bulk density.
3. Responsibilities
- Granulation Personnel: Responsible for preparing the granule sample, performing the bulk density determination, and documenting the results.
- Quality Control (QC): Ensures that the bulk density measurements are taken according to this SOP and that the results are within the specified range.
- Quality Assurance (QA): Reviews the bulk density determination results to ensure compliance with the product specifications and regulatory requirements.
4. Accountability
The Production Manager is accountable for ensuring the bulk density determination process is conducted as per this SOP. The QA Manager is responsible for reviewing the results and ensuring all required records are maintained.
5. Procedure
5.1 Preparation for Bulk Density Measurement
- Ensure that all equipment, including a 100 mL graduated cylinder, balance, and spatula, is clean and calibrated as per the equipment calibration SOP.
- Prepare the granule sample to be used for the bulk density measurement. The sample should be free of lumps or clumps, and the granules should be properly mixed.
- Weigh an empty graduated cylinder to the nearest gram and record the weight in the batch record (Annexure-1).
- Fill the graduated cylinder with the granules, ensuring the granules are added in a consistent manner (without tapping or compressing) to avoid altering their bulk density.
- Record the volume occupied by the granules in the graduated cylinder.
5.2 Bulk Density Measurement
- Weigh the cylinder filled with granules to the nearest gram and record the total weight in the batch record (Annexure-1).
- Determine the bulk density using the following formula:
Bulk Density (g/mL) = Weight of Granules (g) / Volume of Granules (mL)
- Repeat the measurement for at least three different samples to ensure accuracy and calculate the average bulk density of the granules.
- Ensure that the bulk density of the granules falls within the acceptable range specified for the formulation (typically 0.4 g/mL to 0.6 g/mL for most tablet granulations).
5.3 Documentation and Record-Keeping
- Document the weight of the empty cylinder, the weight of the filled cylinder, and the calculated bulk density in the batch record (Annexure-1).
- Record any deviations from the specified bulk density range and the actions taken to address them.
- Ensure that the records are reviewed and signed off by the responsible personnel and that the bulk density data is stored for future reference and audit purposes.
5.4 Equipment Cleaning
- After completing the bulk density determination, clean all equipment thoroughly to prevent contamination during subsequent measurements. Follow the equipment cleaning SOP to ensure proper cleaning of the graduated cylinder and balance.
- Document the cleaning activities in the cleaning log (Annexure-2), ensuring compliance with regulatory standards.
5.5 Frequency of Bulk Density Determination
- Bulk density should be determined for every new batch of granules before the granulation process moves forward. If significant changes in the formulation or process are made, the bulk density should be re-measured to ensure it meets the required specifications.
6. Abbreviations
- SOP: Standard Operating Procedure
- GMP: Good Manufacturing Practice
- QC: Quality Control
- QA: Quality Assurance
- API: Active Pharmaceutical Ingredient
7. Documents
- Batch Record (Annexure-1)
- Cleaning Log (Annexure-2)
8. References
- 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
- EU GMP Guidelines Part I – Basic Requirements for Medicinal Products
- ICH Q7 – Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Batch Record
| Batch Number | Granule Type | Weight of Empty Cylinder (g) | Weight of Filled Cylinder (g) | Bulk Density (g/mL) | Remarks |
|---|---|---|---|---|---|
| Batch 001 | Granule A | 100.0 | 150.5 | 0.52 | Within specifications |
| Batch 002 | Granule B | 100.0 | 151.0 | 0.53 | Within specifications |
Annexure-2: Cleaning Log
| Cleaning Date | Equipment | Cleaning Type | Performed By | Remarks |
|---|---|---|---|---|
| 01/06/2025 | Graduated Cylinder | Routine Cleaning | John Doe | Performed as per SOP |
| 02/06/2025 | Balance | Routine Cleaning | Jane Smith | No issues found |
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 Granule Sample Preparation Method | Granulation Process Optimization | QA Head |