Frequently Asked Questions on Dissolution
Q. What is dissolution testing, and why is it important?
Dissolution testing is a critical quality control measure in pharmaceutical manufacturing that evaluates how quickly an active pharmaceutical ingredient (API) releases from its dosage form. It ensures product efficacy, consistency, and patient safety.
Q. What are the stages of dissolution testing?
Dissolution testing occurs in three stages:
- S1 Stage (6 units): All 6 dosage units must meet or exceed the specified Q value (typically 75-80%). If not, proceed to S2.
- S2 Stage (12 units total, including S1 units): The average dissolution must be at least Q, and no unit can be below Q-15%. If criteria are not met, proceed to S3.
- S3 Stage (24 units total, including S1 and S2 units): The average dissolution must be at least Q, no more than 2 units can be below Q-15%, and no unit can be below Q-25%.
Q. What steps should be taken when there is a failure at the S1 stage?
- Initial Assessment: Document failure details and quarantine the batch.
- Escalate to S2 Testing: Test 6 additional units under the same conditions.
- Preliminary Investigation: Identify potential causes such as formulation, manufacturing, or analytical errors.
- Risk Assessment: Evaluate the potential impact on quality and safety.
Q. What actions are necessary when there is a failure at the S2 stage?
- Extended Batch Quarantine: Prevent distribution and assess related batches.
- Formal Investigation Launch: Assemble a multidisciplinary team to investigate.
- Expanded Testing: Perform additional tests like disintegration and content uniformity.
- S3 Testing Preparation: Ensure optimal testing conditions and review validation methods.
Q. What happens if a batch fails at the S3 stage?
- Batch Rejection: Document rejection and update inventory systems.
- Root Cause Analysis: Use tools like fishbone diagrams and FMEA to identify issues.
- Regulatory Notification: Report the issue as required by regulatory agencies.
- Corrective and Preventive Actions (CAPA): Implement process improvements.
- Process Review: Evaluate and enhance manufacturing and quality control methods.
Q. Can you provide an example of an S2 stage failure?
- Scenario: A batch of Metoprolol XL 100mg tablets (Batch B2023-045) failed S1 due to two units releasing less than 80% of the API.
- S2 Results: The average dissolution of 12 units was 76%, with three units below Q-15% (65%), leading to S3 testing.
- Investigation Findings: The issue was traced to variability in hydroxypropyl methylcellulose (HPMC) viscosity from a new supplier.
- Resolution: The batch was rejected, supplier qualification procedures were improved, and viscosity specifications were tightened.
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