reproducible dissolution profiling.

2. Scope

This procedure applies to all oral solid dosage forms (tablets, capsules, granules) evaluated within the Analytical Method Development (AMD) department for new and generic drug development programs.

3. Responsibilities

• Analytical Scientist: Executes solubility and sink studies, performs calculations, and recommends media suitability.
• Reviewer: Verifies results and interpretations and confirms alignment with regulatory definitions.
• QA Officer: Ensures the study is adequately documented for regulatory submission.
• Head – AMD: Approves the use of selected dissolution media based on sink condition data.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring that all sink condition evaluations are conducted as per ICH, WHO, and FDA guidelines, and that appropriate decisions are made regarding dissolution media selection.

5. Procedure

5.1 Definition of Sink Condition

1. Sink condition exists when the volume of the dissolution medium can dissolve at least three times the amount of drug substance in the dosage form.
2. This ensures a constant concentration gradient and prevents saturation of the medium.
3. The formula is: Sink Ratio = Solubility in Medium (mg/mL) / Required Concentration (mg/mL)
4. If Sink Ratio ≥ 3, sink conditions are considered achieved.

5.2 Solubility Determination

1. Prepare a series of media based on preliminary selection:
   • Purified water
   • 0.1N HCl
   • pH 4.5 acetate buffer
   • pH 6.8 phosphate buffer
   • 0.5% SLS in water (for poorly soluble APIs)
2. Add excess API (approx. 5–10 times dose equivalent) into 100 mL of each medium.
3. Shake at 100 rpm in a water bath shaker at 37 ± 0.5°C for 24 hours.
4. Filter using 0.45 µm membrane filter, dilute appropriately, and analyze by validated UV or HPLC method.
5. Record results in Annexure-1: Solubility Data Sheet.

5.3 Dose/Solubility Ratio Calculation

1. Determine the drug strength (e.g., 100 mg per tablet) and solubility value (mg/mL).
2. Calculate required volume to dissolve one dose: Dose (mg) ÷ Solubility (mg/mL).
3. Determine if the standard dissolution volume (e.g., 900 mL) exceeds three times this value.
4. Document calculation in Annexure-2: Sink Ratio Evaluation Form.

5.4 Interpretation of Results

1. If sink condition is achieved in a compendial medium, proceed with method development using that medium.
2. If sink condition is not achieved:
   • Consider addition of surfactant
   • Change pH or buffer strength
   • Explore use of biorelevant media (FaSSIF/FeSSIF)
3. Document all justification and supporting data in Annexure-3: Sink Condition Justification Log.

5.5 Documentation and Finalization

1. Compile all solubility, calculation, and decision logs.
2. Include in the method development report and submit to QA and Regulatory Affairs for filing support.
3. Approved dissolution medium and sink condition rationale must be archived as per data retention policy.

6. Abbreviations

• API: Active Pharmaceutical Ingredient
• SLS: Sodium Lauryl Sulfate
• FaSSIF: Fasted-State Simulated Intestinal Fluid
• FeSSIF: Fed-State Simulated Intestinal Fluid
• HPLC: High Performance Liquid Chromatography
• SOP: Standard Operating Procedure

7. Documents

1. Solubility Data Sheet – Annexure-1
2. Sink Ratio Evaluation Form – Annexure-2
3. Sink Condition Justification Log – Annexure-3

8. References

• ICH Q6A – Specifications: Test Procedures and Acceptance Criteria
• USP <711> – Dissolution
• FDA Dissolution Testing of Immediate Release Solid Oral Dosage Forms (1997)
• 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: Solubility Data Sheet

Medium	pH	Solubility (mg/mL)	Temperature (°C)	Result
0.1N HCl	1.2	5.4	37	Pass
pH 6.8 buffer	6.8	1.1	37	Fail

Annexure-2: Sink Ratio Evaluation Form

Dose Strength (mg)	Solubility (mg/mL)	Required Volume (mL)	Dissolution Volume (mL)	Sink Ratio	Status
100	5.4	18.52	900	48.6	Sink Achieved

Annexure-3: Sink Condition Justification Log

In pH 6.8 buffer, sink condition not achieved (Sink Ratio = 1.2). Media modified to include 0.5% SLS. New solubility = 6.2 mg/mL. Sink condition achieved (Sink Ratio = 55.3). Justification: surfactant addition supported by BCS Class II profile and FDA recommendations.

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Expanded annexures and added solubility testing detail	Annual SOP Review