FDA guidance.

2. Scope

This SOP is applicable to all solid oral dosage forms developed and tested within the Analytical Method Development (AMD) department that require a dissolution method capable of detecting meaningful product changes.

3. Responsibilities

• Analytical Scientist: Conducts pre-formulation experiments and method development studies.
• Formulation Scientist: Provides variant batches for discrimination testing.
• Group Leader: Reviews the discriminatory power of the method and supervises optimization.
• QA Executive: Verifies protocol adherence and approves final method parameters.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring that discriminatory dissolution methods are developed and validated before their application in formulation optimization and stability studies.

5. Procedure

5.1 Pre-requisites

1. Obtain the following:
   • Innovator product profile (if applicable)
   • Batches with formulation/process variability (e.g., hardness, binder content)
   • Validated assay method for quantitation

5.2 Initial Method Screening

1. Screen media options:
   • 0.1N HCl
   • Acetate buffer (pH 4.5)
   • Phosphate buffer (pH 6.8)
   • Water or surfactant-containing media (e.g., 0.5% SLS)
2. Select appropriate dissolution apparatus:
   • USP Apparatus I (Basket) or Apparatus II (Paddle)
3. Optimize:
   • Volume (500 mL, 900 mL, etc.)
   • RPM (typically 50–100)
   • Sampling points (5, 10, 15, 30, 45, 60 min)

5.3 Discriminatory Power Evaluation

1. Perform dissolution runs on:
   • Reference/target batch
   • Formulation variant (e.g., lower binder)
   • Process variant (e.g., over-lubricated)
2. Compare profiles using:
   • Mean % release
   • Similarity factor (f2) – f2 < 50 indicates discrimination
   • Variance and time-point comparison
3. Ensure method captures small but meaningful differences in formulation/process.

5.4 Method Optimization and Finalization

1. Refine selected conditions to ensure robustness.
2. Confirm sink conditions and filter compatibility.
3. Conduct repeatability (6 units) and intermediate precision (2 analysts or days).
4. Document all details in Annexure-1 and discrimination results in Annexure-2.

6. Abbreviations

• SOP: Standard Operating Procedure
• RPM: Revolutions Per Minute
• SLS: Sodium Lauryl Sulfate
• f2: Similarity Factor
• ICH: International Council for Harmonisation

7. Documents

1. Dissolution Method Development Worksheet – Annexure-1
2. Discrimination Evaluation Summary – Annexure-2
3. Media Compatibility and Sink Condition Log – Annexure-3

8. References

• ICH Q6A: Specifications – Test Procedures and Acceptance Criteria
• WHO TRS 992 – Annex 3: Dissolution Test Guidance
• FDA Guidance: Dissolution Testing of Immediate Release Solid Oral Dosage Forms

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Tanvi Patel	Rahul Mehta	Sunita Reddy
Designation	Method Development Scientist	QA Reviewer	Head – AMD
Department	Analytical Method Development	QA	Analytical Method Development

11. Annexures

Annexure-1: Dissolution Method Development Worksheet

Media	Apparatus	Volume (mL)	RPM	Time Points (min)	Filter Type
Phosphate Buffer pH 6.8	Apparatus II	900	75	5, 10, 20, 30	0.45 µm Nylon

Annexure-2: Discrimination Evaluation Summary

Batch Type	Mean % Release @ 30 min	f2 vs. Reference	Conclusion
Reference	95.2%	—	—
Binder-Reduced	88.4%	42	Discriminatory
Over-Lubricated	81.1%	36	Discriminatory

Annexure-3: Media Compatibility and Sink Condition Log

Media	Drug Solubility	Sink Achieved?	Remarks
0.1N HCl	5 mg/mL	Yes	Preferred for acid-labile APIs
Water + 0.5% SLS	8 mg/mL	Yes	Used for poorly soluble drug

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
21/05/2025	2.0	Added f2 comparison and annexure tables	Annual SOP Review	Sunita Reddy
04/05/2022	1.0	Initial SOP Release	New Document	QA Head