performance prediction.

2. Scope

This procedure applies to all solid oral dosage forms tested in the Analytical Method Development (AMD) department for dissolution profiling, including immediate-release and modified-release formulations.

3. Responsibilities

• Analytical Scientist: Conducts visual and microscopic assessment of de-aggregation during dissolution testing.
• Formulation Scientist: Provides details on excipient blend, granule hardness, and coating composition that may affect disintegration.
• Group Leader: Reviews evaluation results and recommends media or method adjustments if needed.
• QA Executive: Ensures compliance with protocol and approves final assessment reports.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring de-aggregation is appropriately assessed and documented during dissolution method development and validation.

5. Procedure

5.1 Selection of Samples and Dissolution Conditions

1. Select representative lots of tablets or capsules (minimum 6 units).
2. Conduct testing under proposed dissolution conditions:
   • Apparatus (e.g., USP I or II)
   • Media (e.g., 900 mL, 0.1N HCl, pH 6.8 buffer)
   • Temperature: 37 ± 0.5°C
   • RPM: 50–100 (as per method)

5.2 Visual and Physical Monitoring

1. Observe each dosage form during dissolution at defined time points:
   • Initial wetting
   • Disintegration pattern
   • Swelling, floating, gelling behavior
2. Record observations using Annexure-1: De-aggregation Observation Log.

5.3 Filter Analysis

1. At key time points, withdraw samples and filter through pre-weighed 0.45 µm filters.
2. Weigh retained particles to assess incomplete de-aggregation (Annexure-2).
3. Optionally, perform microscopic examination of residue for excipient agglomerates.

5.4 Method Optimization if De-aggregation Fails

1. Adjust one or more of the following parameters:
   • Media volume and type (increase to 1000–1500 mL or add surfactant)
   • Apparatus type (change from paddle to basket or reciprocating cylinder)
   • RPM adjustment to enhance agitation
2. Repeat observation and filter analysis post-adjustment.

5.5 Documentation

1. Summarize findings in Annexure-3: De-aggregation Evaluation Report.
2. Attach photographic or video evidence if available.
3. Ensure QA review and approval of the report before method finalization.

6. Abbreviations

• SOP: Standard Operating Procedure
• AMD: Analytical Method Development
• RPM: Revolutions Per Minute
• USP: United States Pharmacopeia

7. Documents

1. De-aggregation Observation Log – Annexure-1
2. Filter Residue Weighing Log – Annexure-2
3. Evaluation Summary Report – Annexure-3

8. References

• USP General Chapter <1092> – The Dissolution Procedure: Development and Validation
• FDA Dissolution Testing Guidance
• ICH Q6A – Specifications

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Ankita Sharma	Ravi Shankar	Sunita Reddy
Designation	Research Scientist	QA Reviewer	Head – AMD
Department	Analytical Method Development	QA	Analytical Method Development

11. Annexures

Annexure-1: De-aggregation Observation Log

Unit No.	Time Point (min)	Observation	Notes
1	10	Partial disintegration, fragments visible	Coating delayed swelling

Annexure-2: Filter Residue Weighing Log

Time (min)	Filter ID	Initial Wt (mg)	Final Wt (mg)	Residue (mg)
30	FR-217-05	102.3	104.8	2.5

Annexure-3: De-aggregation Evaluation Summary

All units showed complete disintegration within 30 min. Residual particles were < 3 mg, confirming adequate de-aggregation. No method modification required. Photographic records stored in: AMD/DEAGG/217/2025

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
21/05/2025	2.0	Included filter quantification and digital image documentation	Annual Review	Sunita Reddy
14/04/2022	1.0	Initial Issue	New SOP	QA Head