SOP for pH Method Development of Pharmaceutical Formulations in AMD Laboratory

Department	Analytical Method Development
SOP No.	SOP/AMD/043/2025
Supersedes	SOP/AMD/043/2022
Page No.	Page 1 of 14
Issue Date	19/05/2025
Effective Date	20/05/2025
Review Date	19/05/2026

1. Purpose

This SOP describes the process for developing and validating robust pH measurement methods for pharmaceutical formulations. The procedure ensures accurate and reproducible pH readings that reflect formulation stability, performance, and regulatory expectations.

2. Scope

This SOP is applicable to all oral, parenteral, topical, ophthalmic, and other dosage forms developed in the AMD laboratory where pH measurement is critical for product characterization, compatibility, or stability testing.

3. Responsibilities

• Formulation Scientist: Provides formulation composition and trial samples.
• Analytical Scientist: Conducts pH method development and records all experiments and observations.
• QA: Reviews and approves validation documentation.
• Head – AMD: Ensures pH method is fit-for-purpose and included in development reports.

4. Accountability

The Head of AMD is accountable for ensuring that all pH methods developed for formulations are scientifically justified, reproducible, and meet global regulatory standards for analytical method validation.

5. Procedure

5.1 Pre-Development Strategy

1. Understand dosage form type (solution, suspension, emulsion, gel, ointment).
2. Identify critical formulation components affecting pH (buffer, preservatives, excipients).
3. Select pH range based on:
   • Formulation stability and performance
   • Pharmacopoeial monographs
   • Target therapeutic window (e.g., ophthalmic pH 6.5–7.5)
4. Record the strategy in Annexure-1: Formulation pH Development Plan.

5.2 Sample Preparation

1. Use formulation batch as-is, or dilute with water/buffer (e.g., 1:10 dilution for creams or suspensions).
2. For emulsions, allow phase separation or centrifugation if needed.
3. Ensure uniformity before sampling using gentle stirring.

5.3 pH Measurement

1. Calibrate pH meter with at least 2 standard buffers before use (4.01, 7.00, 9.21).
2. Document calibration in Annexure-2: pH Meter Calibration Log.
3. Transfer 50 mL of formulation or sample solution into a clean beaker.
4. Immerse electrode completely and swirl gently.
5. Wait for reading to stabilize (generally within 60 seconds).
6. Record pH value and temperature of measurement (e.g., 25°C ± 2°C).
7. Rinse electrode with deionized water after each reading.

5.4 Method Optimization

1. Test pH response across multiple formulation batches to confirm reproducibility.
2. Assess impact of temperature (20–30°C) and dilution factor on pH.
3. Determine method response under light agitation or stirring (for semi-solids).
4. Document trials in Annexure-3: pH Optimization Worksheet for Formulations.

5.5 Method Validation Parameters

1. Linearity: Not applicable for pH, but confirm consistency across pH 2–10 range with known standards.
2. Precision: Repeatability (6 readings) and intermediate precision (2 analysts, different instruments).
3. Robustness: Vary electrode type, temperature, and assess pH variation.
4. Accuracy: Compare pH with pharmacopoeial range or known validated method.
5. Document results in Annexure-4: pH Method Validation Report.

5.6 Method Finalization and Approval

1. Consolidate and draft method SOP with:
   • Sample volume and preparation
   • Buffer system (if any)
   • pH range and acceptance limits
   • Cleaning and calibration instructions
2. Submit to QA for review and include approved method in product development dossier.

6. Abbreviations

• AMD: Analytical Method Development
• QA: Quality Assurance
• SOP: Standard Operating Procedure
• API: Active Pharmaceutical Ingredient

7. Documents

1. Formulation pH Development Plan – Annexure-1
2. pH Meter Calibration Log – Annexure-2
3. pH Optimization Worksheet for Formulations – Annexure-3
4. pH Method Validation Report – Annexure-4

8. References

• USP <791> – pH
• ICH Q2(R1) – Validation of Analytical Procedures
• WHO Technical Report Series 1019
• 21 CFR Part 211 – Laboratory Controls

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Formulation pH Development Plan

Formulation	Matrix	Target pH Range	Prepared By
Ophthalmic Gel	Carbomer-Based	6.8–7.2	Meenal Patil

Annexure-2: pH Meter Calibration Log

Date	Buffer Used	Observed Reading	Calibrated By
03/05/2025	pH 4.01	4.00	Rajesh Kumar
03/05/2025	pH 7.00	7.02	Rajesh Kumar

Annexure-3: pH Optimization Worksheet for Formulations

Formulation	Temperature (°C)	pH	Remarks
Oral Suspension	25	4.5	Stable reading
Oral Suspension	30	4.4	Acceptable deviation

Annexure-4: pH Method Validation Report

Validation Parameter	Acceptance Criteria	Results	Status
Precision	RSD ≤ 1.0%	0.38%	Pass
Robustness	pH variation ≤ ±0.1	±0.08	Pass

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Updated to include validation parameters and buffer compatibility	ICH Q2 alignment