Officer: Oversight of documentation, sampling, and in-process quality checks.

QC Analyst: Analyze and verify pH responsiveness and consistency.

4. Accountability

The Head – Manufacturing shall be accountable for the implementation, compliance, and performance of this SOP, ensuring final product readiness for release.

5. Procedure

5.1 Selection of pH-Sensitive Components

1. Select polymer systems that respond to pH, such as Eudragit®, Chitosan, or Carbopol® with appropriate functional groups (e.g., carboxylic acids, amines).
2. Determine the desired pH trigger for drug release (e.g., acidic for stomach, alkaline for intestine).

5.2 Weighing and Dispensing

1. Weigh all raw materials including API, polymers, pH modifiers, and solvents in a designated area.
2. Ensure that all materials are within expiry and meet the specifications as per the MFR.

5.3 Gel Base Preparation

1. Dissolve or disperse the selected polymer in a suitable vehicle (e.g., water or ethanol) using a low-shear stirrer to prevent air entrapment.
2. Allow hydration of the polymer for the time defined in the BMR (e.g., 2–4 hours).
3. Use cooling jacketed mixing vessels if heat is generated during hydration.

5.4 API Incorporation

1. Introduce API under slow stirring to avoid agglomeration or degradation.
2. Use homogenization or ultrasonication where specified for better drug dispersion.

5.5 pH Adjustment

1. Adjust the final pH using triethanolamine (TEA), HCl, or NaOH depending on formulation design.
2. Record final pH using a calibrated digital pH meter, targeting specified range (e.g., 5.5–6.5).

5.6 In-Process Testing

1. Check gel appearance, clarity, and viscosity.
2. Conduct sample drug release studies in media simulating different pH environments (e.g., SGF and SIF).

5.7 Filling and Labeling

1. Fill gels into pre-cleaned laminated tubes using a calibrated semi-automatic filling machine.
2. Label all containers with product name, batch number, mfg. date, exp. date, and storage instructions.

5.8 Documentation and Cleaning

1. Document all activities in the BMR and logbooks.
2. Clean all utensils, equipment, and vessels as per the respective cleaning SOPs.

6. Abbreviations

• API: Active Pharmaceutical Ingredient
• BMR: Batch Manufacturing Record
• QA: Quality Assurance
• QC: Quality Control
• SGF: Simulated Gastric Fluid
• SIF: Simulated Intestinal Fluid

7. Documents

1. Master Formula Record – Annexure-1
2. Weighing Log Sheet – Annexure-2
3. Batch Manufacturing Record – Annexure-3
4. pH Adjustment Log – Annexure-4
5. In-Process Control Sheet – Annexure-5

8. References

• USP General Chapter <711> Dissolution Testing
• ICH Q8(R2) – Pharmaceutical Development
• 21 CFR Part 211 – Current Good Manufacturing Practice

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation	Product Development Chemist	QA Executive	Head – Manufacturing
Department	Gel Manufacturing	Quality Assurance	Manufacturing

11. Annexures

Annexure-1: Master Formula Record

Component	Qty/Batch	Function

Annexure-2: Weighing Log Sheet

Material	Qty	Batch No.	Weighed By

Annexure-3: BMR Format

Stage	Observation	Operator	Date

Annexure-4: pH Adjustment Log

Initial pH	Adjusting Agent	Final pH	Adjusted By

Annexure-5: In-Process Control Sheet

Parameter	Specification	Observed	Remarks
pH	5.5–6.5
Viscosity	As per MFR

Revision History

Revision Date	Revision No.	Description of Change	Reason	Approved By
20/06/2022	1.0	Initial version released	New pH-sensitive product	QA Head
09/06/2025	2.0	Updated to include simulated media testing	Process Enhancement	QA Head