relevance to gastrointestinal physiology, and method robustness.

2. Scope

This SOP applies to all dissolution method development activities conducted in the Analytical Method Development (AMD) department for tablets, capsules, and similar dosage forms intended for oral administration.

3. Responsibilities

• Analytical Scientist: Conducts solubility and discriminatory media studies.
• Formulation Scientist: Provides formulation details, drug properties, and excipient profiles.
• Reviewer: Evaluates justification of media selection and ensures regulatory compliance.
• Head – AMD: Approves the finalized dissolution media and method development protocol.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring the scientific appropriateness and regulatory alignment of the dissolution media selected during method development and validation.

5. Procedure

5.1 Initial Data Collection

1. Obtain the following:
   • Drug substance pKa, solubility data (aqueous and pH range)
   • BCS classification and log P value
   • Dose strength and dosage form design
2. Review relevant pharmacopeial monographs and prior art.
3. Record details in Annexure-1: Preformulation Data Sheet.

5.2 Solubility Screening

1. Conduct preliminary solubility screening in:
   • Purified water
   • 0.1N HCl
   • Simulated gastric fluid (SGF) and simulated intestinal fluid (SIF)
   • Buffers: pH 1.2, 4.5, 6.8, 7.4
   • Media with surfactants (e.g., 0.5% SLS, 1% Tween 80) if required
2. Equilibrate drug with 250 mL of medium at 37 ± 0.5°C for 24 hours under agitation.
3. Filter, dilute, and analyze using UV or HPLC.
4. Document in Annexure-2: Solubility Screening Log.

5.3 Sink Condition Evaluation

1. Define sink condition: at least three times the highest dose of drug should dissolve in selected volume (typically 900 mL).
2. Calculate solubility/dose ratio and determine if sink conditions are met.
3. If not met, explore options:
   • Change buffer pH or type
   • Add surfactant
   • Use biorelevant media (FaSSIF, FeSSIF)
4. Document sink status in Annexure-3: Sink Condition Evaluation Form.

5.4 Media Discriminatory Power Assessment

1. Run comparative dissolution studies using selected media on:
   • Innovator/reference product (if available)
   • In-house formulations with known variation in critical attributes (e.g., hardness, coating thickness)
2. Select medium that distinguishes minor formulation differences.
3. Document comparative profiles in Annexure-4: Media Discrimination Report.

5.5 Regulatory and Safety Considerations

1. Ensure selected medium is:
   • Pharmacopeial or justified with scientific rationale
   • Non-toxic and non-reactive with API
   • Stable under test conditions
2. If non-compendial media is selected, provide robust justification including physiological relevance, literature references, and discrimination data.
3. Document rationale in Annexure-5: Media Justification Summary.

5.6 Finalization and Approval

1. Compile all annexures and finalize the selected dissolution medium.
2. Record the following:
   • Media composition and pH
   • Volume (typically 500 mL to 1000 mL)
   • Stirring rate and temperature
   • Apparatus type (to be finalized separately)
3. Submit for review and approval by Head – AMD.

6. Abbreviations

• FTIR: Fourier Transform Infrared
• SGF: Simulated Gastric Fluid
• SIF: Simulated Intestinal Fluid
• SLS: Sodium Lauryl Sulfate
• BCS: Biopharmaceutical Classification System
• SOP: Standard Operating Procedure

7. Documents

1. Preformulation Data Sheet – Annexure-1
2. Solubility Screening Log – Annexure-2
3. Sink Condition Evaluation Form – Annexure-3
4. Media Discrimination Report – Annexure-4
5. Media Justification Summary – Annexure-5

8. References

• ICH Q6A – Specifications: Test Procedures and Acceptance Criteria
• FDA Dissolution Testing of Immediate Release Solid Oral Dosage Forms (1997)
• USP <711> – Dissolution
• WHO Technical Report Series 929, Annex 7

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Preformulation Data Sheet

API Name	Example Drug A
pKa	5.8
Log P	2.1
BCS Class	II
Dose	100 mg

Annexure-2: Solubility Screening Log

Medium	pH	Solubility (mg/mL)	Sink Achieved?
0.1N HCl	1.2	4.5	Yes
pH 6.8 buffer	6.8	0.9	No

Annexure-3: Sink Condition Evaluation Form

Medium	Dose (mg)	Volume (mL)	Saturation Solubility	Sink Ratio	Status
0.1N HCl	100	900	4.5 mg/mL	40.5	Sink

Annexure-4: Media Discrimination Report

Media	Batch A (%)	Batch B (%)	Difference	Conclusion
0.1N HCl	85	72	13	Discriminatory

Annexure-5: Media Justification Summary

0.1N HCl was selected based on adequate solubility, sink condition compliance, and discriminatory power between formulation variants. It also mimics gastric conditions, supporting biorelevance.

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Complete format update and annexure expansion for regulatory alignment	Annual SOP Review