formulation robustness and supports dissolution method validation during product development and post-approval changes.

2. Scope

This SOP is applicable to the Analytical Method Development and Quality Control departments performing correlation studies between tablet hardness and dissolution behavior for tablets under development or commercial batches.

3. Responsibilities

• Formulation Scientist: Provides tablets of varying hardness for evaluation.
• Analytical Scientist: Develops and validates method, performs testing, and analyzes data.
• QA Executive: Reviews results and ensures documentation compliance.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring compliance with ICH, FDA, and internal procedures for dissolution studies related to formulation and process optimization.

5. Procedure

5.1 Tablet Hardness Testing

1. Use a calibrated tablet hardness tester (e.g., Monsanto or Pfizer type).
2. Collect 30 tablets from batch; divide into 3 groups of 10 each:
   • Group A: Low hardness (e.g., 3–5 kp)
   • Group B: Medium hardness (target, e.g., 6–8 kp)
   • Group C: High hardness (e.g., 9–12 kp)
3. Document individual hardness readings in Annexure-1.

5.2 Dissolution Testing

1. Use USP Apparatus II (Paddle) with 900 mL media (e.g., pH 6.8 buffer) at 37 ± 0.5°C and 50–75 rpm.
2. Conduct dissolution runs separately for each group.
3. Withdraw samples at 5, 10, 15, 30, and 45 minutes.
4. Filter samples and analyze by UV or HPLC based on established assay method.

5.3 Data Analysis

1. Calculate % drug release at each time point for all 3 hardness groups.
2. Plot dissolution profiles and compare using f₂ similarity factor if applicable.
3. Analyze correlation between hardness and % release using linear regression.

5.4 Acceptance Criteria

• Tablet hardness should not significantly impact dissolution rate for robust formulations.
• f₂ value between profiles of groups B and C should be ≥50.
• API release for all hardness groups should meet Q value criteria (e.g., NLT 80% in 45 minutes).

5.5 Validation Parameters

1. Specificity: No interference at detection wavelength or retention time.
2. Precision: RSD ≤ 2% within each group.
3. Robustness: Evaluate at ±5 rpm and ±0.1 pH for dissolution media.

6. Abbreviations

• USP: United States Pharmacopeia
• f₂: Similarity factor
• kp: Kilopond (unit of hardness)
• RSD: Relative Standard Deviation

7. Documents

1. Tablet Hardness and Grouping Log – Annexure-1
2. Dissolution Result Table – Annexure-2
3. Statistical and Graphical Analysis – Annexure-3

8. References

• USP <701>: Disintegration
• USP <711>: Dissolution
• ICH Q6A: Specifications – Test Procedures and Acceptance Criteria

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Abhishek Rawat	Sneha Dixit	Sunita Reddy
Designation	Analytical Scientist	QA Reviewer	Head – AMD
Department	Analytical Method Development	QA	Analytical Method Development

11. Annexures

Annexure-1: Tablet Hardness and Grouping Log

Tablet No.	Hardness (kp)	Group
1	5.2	A
2	6.8	B
3	10.1	C

Annexure-2: Dissolution Result Table

Time (min)	Group A (%)	Group B (%)	Group C (%)
15	64%	58%	49%
30	85%	81%	72%
45	96%	94%	89%

Annexure-3: Statistical and Graphical Analysis

Regression analysis shows a negative correlation between hardness and dissolution rate (R² = 0.91). f₂ value between Groups B and C = 65, indicating acceptable similarity.

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
21/05/2025	2.0	Added statistical comparison and f2 threshold interpretation	Annual Review	Sunita Reddy
25/10/2022	1.0	Initial SOP Release	New SOP	QA Head