ensure method robustness, consistent drug release, and compliance with ICH, WHO, and USP guidelines.

2. Scope

This SOP applies to all dissolution media developed and used in the Analytical Method Development (AMD) department for oral solid dosage forms requiring buffer-based media.

3. Responsibilities

• Analytical Chemist: Prepares, evaluates, and documents buffer media pH and capacity results.
• Formulation Scientist: Provides drug solubility, pKa, and expected GI site of absorption.
• Group Leader: Reviews selection rationale and buffer capacity profiles.
• QA Executive: Verifies compliance of buffer systems with internal and regulatory expectations.

4. Accountability

The Head of Analytical Method Development is accountable for approving the use of selected pH conditions and buffer systems in dissolution methods prior to validation or regulatory submission.

5. Procedure

5.1 Selection of pH for Dissolution Media

1. Choose media based on drug pKa, solubility profile, and site of absorption:
   • pH 1.2 (gastric), pH 4.5 (upper intestine), pH 6.8 (lower intestine)
   • Use biorelevant media (e.g., FaSSIF, FeSSIF) if required for BCS Class II/IV drugs
2. Document rationale for pH selection based on drug properties and physiological conditions (Annexure-1).

5.2 Preparation of Buffer Media

1. Prepare buffer systems using standard reagents:
   • pH 4.5: Acetate buffer
   • pH 6.8: Phosphate buffer
   • pH 7.5–8.0: Tris buffer (if needed)
2. Verify final pH using calibrated pH meter and adjust ±0.05 with HCl or NaOH.

5.3 Evaluation of Buffer Capacity

1. Perform buffer capacity testing for each prepared media as follows:
   • Take 50 mL of buffer media in a beaker
   • Add 0.1 mL increments of 0.1N HCl or 0.1N NaOH
   • Record pH after each addition until ±1.0 pH unit change is observed
2. Plot pH vs. volume of acid/base added to determine buffering range and capacity.
3. Ensure buffer capacity is within acceptable range (0.01–0.05 mmol/mL/pH unit) for dissolution relevance.

5.4 Finalization and Documentation

1. Finalize selected buffer pH and strength (e.g., 50 mM, 100 mM) based on solubility and stability data.
2. Document pH selection, buffer strength, and capacity results in Annexure-2 and Annexure-3.
3. Store prepared media in amber carboys labeled with pH, strength, and expiry.

6. Abbreviations

• SOP: Standard Operating Procedure
• pKa: Acid dissociation constant
• GI: Gastrointestinal
• BCS: Biopharmaceutics Classification System
• FaSSIF: Fasted State Simulated Intestinal Fluid
• FeSSIF: Fed State Simulated Intestinal Fluid

7. Documents

1. Media pH Selection Justification – Annexure-1
2. Buffer Capacity Evaluation Log – Annexure-2
3. Buffer Titration Graphs – Annexure-3

8. References

• USP General Chapters <711> and <1092>
• FDA Dissolution Testing of Immediate Release Solid Oral Dosage Forms
• WHO TRS 992 – Annex 3

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Manisha Tiwari	Arvind Chauhan	Sunita Reddy
Designation	Scientific Officer	QA Reviewer	Head – AMD
Department	Analytical Method Development	QA	Analytical Method Development

11. Annexures

Annexure-1: Media pH Selection Justification

Drug	pKa	Target Site	Selected pH	Justification
Ciprofloxacin	6.1	Small Intestine	6.8	Solubility and absorption optimized

Annexure-2: Buffer Capacity Evaluation Log

Media	pH Range	Base/Acid Added	Buffer Capacity (mmol/mL/pH)
Phosphate Buffer	6.5–7.5	0.8 mL NaOH	0.031

Annexure-3: Buffer Titration Graph Summary

Graphs archived in AMD/BUFFER/GRAPH/215/2025 and digitally signed by QA.

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
21/05/2025	2.0	Included buffer capacity quantification and digital annexure archiving	Annual Review	Sunita Reddy
18/05/2022	1.0	Initial Release	New SOP	QA Head