Standard Operating Procedure for End-Point Determination in Granulation Process
| Department | Tablet |
|---|---|
| SOP No. | SOP/TAB/023/2025 |
| Supersedes | SOP/TAB/023/2022 |
| Page No. | Page 1 of 7 |
| Issue Date | 03/06/2025 |
| Effective Date | 08/06/2025 |
| Review Date | 03/06/2026 |
1. Purpose
This SOP defines the procedures for determining the end-point in the granulation process, ensuring that granules achieve the desired physical properties, such as size, moisture content, and flowability, before moving to the next stage of tablet manufacturing.
2. Scope
This SOP applies to the granulation process during tablet manufacturing, including wet and dry granulation methods. It covers techniques for determining the end-point of granulation based on granule quality parameters.
3. Responsibilities
- Granulation Personnel: Responsible for monitoring and adjusting the granulation process, ensuring that granules meet the required specifications before the process is considered complete.
- Quality Control (QC): Conducts testing and verifies that the granulation process has achieved the desired characteristics, including moisture content, particle size distribution, and flowability.
- Quality Assurance (QA): Ensures that the granulation process complies with this SOP, and reviews process records to confirm that all parameters are within acceptable limits.
4. Accountability
The Production Manager is accountable for ensuring that the granulation process is completed per this SOP, while the QA Manager is responsible for ensuring compliance and reviewing the final granulation results.
5. Procedure
5.1 Granulation Preparation
- Ensure that all raw materials for granulation are weighed accurately and meet the required specifications.
- Prepare the granulation equipment, including the granulator, mixer, and drying units, ensuring they are clean and properly calibrated.
- Verify that the binder solution and excipients are mixed to the correct consistency before being introduced into the granulation process.
5.2 Monitoring Granule Formation
- During the granulation process, monitor the mixing time and granulation conditions (e.g., temperature, humidity) to ensure that the granules form consistently.
- Take random samples of granules at regular intervals and check their size, appearance, and moisture content using standard operating procedures for sampling.
- If the granules appear too wet or sticky, adjust the binder addition or reduce the mixing time to achieve the desired consistency.
5.3 Determining End-Point Based on Granule Size
- Use a sieve or particle size analyzer to measure the granule size at various intervals during the process.
- Ensure that the granules fall within the specified size range as defined by the product formula, typically 0.2mm to 1.5mm, depending on the tablet specifications.
- If the granule size is smaller or larger than the required range, adjust the process parameters (e.g., binder addition, mixing speed) to ensure consistency.
- Once the granules meet the desired size distribution, consider the granulation process to be nearing completion.
5.4 Moisture Content Determination
- Test the moisture content of granules using a moisture analyzer or Karl Fischer titration at specified intervals during granulation.
- Ensure that the moisture content falls within the acceptable range (typically between 1% to 5% for most formulations), depending on the type of granulation.
- Adjust the drying conditions if the moisture content exceeds the acceptable limits. If the granules are too dry, consider adding more binder solution to achieve the proper consistency.
- Once the desired moisture content is reached, stop the granulation process and proceed to the next step in the tablet manufacturing process.
5.5 Flowability and Uniformity Check
- Measure the flowability of the granules by performing a simple flow test, such as the Carr Index or the angle of repose test, to ensure that the granules will flow properly during compression.
- Check the uniformity of the granules by sampling from different points in the batch. Ensure that there is no segregation of fine and coarse particles.
- If flowability is poor, adjust the granulation process by adding more excipients, such as lubricants or flow aids, to improve flow properties.
5.6 Final Granulation Inspection and Documentation
- After confirming that all parameters are within specification, proceed with the final inspection of the granules, ensuring that they meet all quality requirements.
- Ensure that the granules are free of lumps, clumps, or excessive moisture, which could affect the tablet compression process.
- Document all the observations, test results, and adjustments made during the granulation process in the batch record (Annexure-1).
5.7 Equipment Shutdown and Cleaning
- After completing the granulation process, shut down the equipment following the standard operating procedure for equipment shutdown and cleaning.
- Ensure that all equipment, including mixers, granulators, and sieves, is thoroughly cleaned to prevent cross-contamination with subsequent batches.
5.8 Documentation and Record-Keeping
- Ensure that all granulation records, including granule size, moisture content, flowability, and any corrective actions taken, are documented in the batch record.
- Review the batch record and ensure that all required tests and inspections have been performed before moving to the next stage of tablet manufacturing.
- Maintain the batch records for audit purposes and ensure compliance with regulatory guidelines.
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)
- Granule Size and Moisture 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 Size (mm) | Moisture Content (%) | Flowability Test | Remarks |
|---|---|---|---|---|
| Batch 001 | 0.5 – 1.0 | 3.5% | Good Flow | Within specifications |
| Batch 002 | 0.6 – 1.2 | 4.2% | Fair Flow | Adjustment made |
Annexure-2: Granule Size and Moisture Log
| Batch Number | Tablet Type | Granule Size | Moisture Content (%) | Remarks |
|---|---|---|---|---|
| Batch 001 | Tablet A | 0.5 mm | 3.5% | Within specifications |
| Batch 002 | Tablet B | 0.7 mm | 4.0% | Adjusted moisture level |
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 Granulation Monitoring Parameters | Process Optimization | QA Head |