and meet regulatory expectations.

2. Scope

This SOP applies to all modified release oral solid dosage forms developed and tested within the Analytical Method Development (AMD) department for routine quality control, stability, and bioequivalence support studies.

3. Responsibilities

• Analytical Scientist: Conducts method screening, optimization, and validation studies.
• Formulation Scientist: Provides batch data and formulation insights for development.
• Group Leader: Reviews design and discrimination capacity of the method.
• QA Executive: Ensures protocol compliance and method suitability.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring that dissolution methods for modified release formulations are appropriately developed, validated, and documented.

5. Procedure

5.1 Understanding the Formulation

1. Review product design and release mechanisms:
   • Matrix, coated, osmotic pump, or multiparticulate system
   • Target release profile and dosage interval (e.g., 12hr, 24hr)

5.2 Media and Apparatus Selection

1. Select dissolution media based on pKa, solubility, and GI physiology:
   • pH 1.2, 4.5, and 6.8 buffers
   • Enzymes or surfactants if required (e.g., 0.1% SLS)
2. Choose suitable apparatus:
   • USP Apparatus I (Basket) or II (Paddle)
   • USP Apparatus III or IV for complex delivery systems (optional)

5.3 Time Point and Duration Optimization

1. Select multiple time points (minimum 6) across entire release period (e.g., 1, 2, 4, 6, 8, 12, 24 hours).
2. Ensure sampling reflects both lag phase (if applicable) and plateau phase.
3. Set sampling intervals according to expected release kinetics (zero-order, first-order, Higuchi, etc.).

5.4 Discriminatory Method Verification

1. Test method on:
   • Reference batch
   • Formulation/process variants (e.g., different granule sizes, coating levels)
2. Evaluate using:
   • f2 similarity factor (target: < 50 for discriminatory batches)
   • Release rate shifts at key time points

5.5 Filter and Sink Condition Confirmation

1. Ensure sink condition (dissolved amount ≤ 30% of drug solubility in media).
2. Verify filter compatibility through recovery studies using spiked solution.

5.6 Documentation and Validation Readiness

1. Compile results in Annexure-1: Method Development Sheet.
2. Prepare preliminary method SOP and draft validation protocol.
3. Submit for internal review and QA assessment.

6. Abbreviations

• SOP: Standard Operating Procedure
• QA: Quality Assurance
• GI: Gastrointestinal
• SLS: Sodium Lauryl Sulfate
• f2: Similarity Factor

7. Documents

1. Modified Release Dissolution Development Log – Annexure-1
2. Discriminatory Evaluation Summary – Annexure-2
3. Media Compatibility and Sink Condition Checklist – Annexure-3

8. References

• ICH Q6A: Specifications – Test Procedures and Acceptance Criteria
• FDA Guidance: Dissolution Testing for Modified Release Products
• WHO TRS 992 – Annex 3: Multisource Dissolution Testing

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Deepika Sinha	Karan Bhagat	Sunita Reddy
Designation	Analytical Scientist	QA Reviewer	Head – AMD
Department	Analytical Method Development	QA	Analytical Method Development

11. Annexures

Annexure-1: Modified Release Dissolution Development Log

Media	pH	Volume	Apparatus	RPM	Time Points
Phosphate Buffer	6.8	900 mL	USP II	50	1, 2, 4, 6, 8, 12 hrs

Annexure-2: Discriminatory Evaluation Summary

Batch	Release @ 6hr	Release @ 12hr	f2 vs. Reference	Status
Reference	65.2%	97.1%	–	Baseline
Over-coated	48.9%	88.4%	41	Discriminatory

Annexure-3: Media Compatibility and Sink Condition Checklist

Media	Drug Solubility	Required for Sink?	Sink Achieved?
pH 6.8 Buffer	6.5 mg/mL	Yes	Yes
pH 1.2 + 0.1% SLS	12 mg/mL	Yes	Yes

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
21/05/2025	2.0	Added Annexures and optimization details	Annual SOP Review	Sunita Reddy
11/04/2022	1.0	Initial Issue	New SOP	QA Head