WHO, and USP regulatory standards.

2. Scope

This SOP is applicable to all dissolution methods developed within the Analytical Method Development (AMD) department, specifically for oral solid dosage forms requiring in vitro drug release evaluation.

3. Responsibilities

• Analytical Chemist: Performs solubility studies and sink condition assessments.
• Group Leader: Reviews and approves the experimental design and results.
• QA Executive: Ensures compliance of sink condition verification process with applicable standards.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring the use of validated dissolution media that fulfill sink condition requirements.

5. Procedure

5.1 Definition of Sink Condition

1. Sink condition exists when the dissolution medium can dissolve at least three times the highest dose strength of the drug substance.
2. Solubility must be determined at the specified test temperature (usually 37 ± 0.5°C).

5.2 Solubility Determination

1. Weigh excess quantity of drug substance (~5–10 times the amount required to achieve expected sink concentration).
2. Add to 250 mL of proposed dissolution media (e.g., 0.1N HCl, pH 4.5 acetate buffer, pH 6.8 phosphate buffer).
3. Agitate using a shaker water bath or magnetic stirrer at 37 ± 0.5°C for 24 hours.
4. Filter the supernatant through a 0.45 µm membrane filter.
5. Dilute appropriately and analyze using a validated method (e.g., UV/HPLC).

5.3 Sink Condition Calculation

1. Calculate the maximum theoretical dose concentration (mg/mL) for the highest strength of the drug.
2. Determine the saturation solubility of the drug (mg/mL) in the selected media.
3. Calculate the sink ratio:
   
   Sink Ratio = Saturation Solubility / Maximum Dose Concentration
4. Acceptance Criteria:
   • Sink condition is met if Sink Ratio ≥ 3

5.4 Alternate Strategies if Sink Not Achieved

1. Modify the dissolution media by:
   • Adding surfactants (e.g., 0.1%–1% Sodium Lauryl Sulfate)
   • Altering pH to enhance solubility
   • Using biorelevant media (FaSSIF/FeSSIF)
2. Repeat the procedure to confirm improved solubility and recalculate sink ratio.

5.5 Documentation

1. Record raw data and calculations in Annexure-1: Sink Condition Verification Worksheet.
2. Summarize media screening results and final media selection in Annexure-2.
3. Attach analytical chromatograms or spectrophotometric results as Annexure-3.

6. Abbreviations

• SOP: Standard Operating Procedure
• AMD: Analytical Method Development
• UV: Ultraviolet Spectroscopy
• HPLC: High Performance Liquid Chromatography
• FaSSIF: Fasted State Simulated Intestinal Fluid
• FeSSIF: Fed State Simulated Intestinal Fluid

7. Documents

1. Sink Condition Verification Worksheet – Annexure-1
2. Media Suitability Summary – Annexure-2
3. Solubility Testing Data/Graphs – Annexure-3

8. References

• ICH Q6A: Specifications – Test Procedures and Acceptance Criteria
• USP General Chapter <711>: Dissolution
• FDA Guidance for Industry: Dissolution Testing

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Ravi Nair	Alka Thakur	Sunita Reddy
Designation	Method Development Analyst	QA Reviewer	Head – AMD
Department	Analytical Method Development	QA	Analytical Method Development

11. Annexures

Annexure-1: Sink Condition Verification Worksheet

Drug	Strength (mg)	Volume (mL)	Max Dose Conc. (mg/mL)	Solubility (mg/mL)	Sink Ratio	Status
Metoprolol	100	900	0.111	0.456	4.1	Pass

Annexure-2: Media Suitability Summary

Media	pH	Solubility (mg/mL)	Sink Achieved?	Remarks
Phosphate Buffer	6.8	0.456	Yes	Suitable for basic drugs
Water + 0.5% SLS	Neutral	1.120	Yes	Used for poorly soluble drugs

Annexure-3: Solubility Testing Data

Analytical data files stored under folder path: AMD/SINK/216/2025. Spectral files archived and cross-referenced with sample ID in validation protocol.

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
21/05/2025	2.0	Updated with solubility testing conditions and digital annexure storage	Annual Review	Sunita Reddy
25/05/2022	1.0	Initial Release	New SOP	QA Head