Standard Operating Procedure for X-Ray Powder Diffraction for API Analysis in Tablets

Department	Quality Control
SOP No.	SOP/TAB/105/2025
Supersedes	SOP/TAB/105/2022
Page No.	Page 1 of 7
Issue Date	01/03/2026
Effective Date	06/03/2026
Review Date	01/03/2027

1. Purpose

To define the procedure for performing X-ray powder diffraction (XRD) analysis for the identification and characterization of the active pharmaceutical ingredient (API) in tablet formulations.

2. Scope

This SOP applies to the use of XRD for the analysis of tablet formulations to verify the presence and purity of the API and identify crystalline forms that may affect bioavailability.

3. Responsibilities

• Quality Control (QC): Responsible for performing XRD analysis on tablet samples, interpreting the results, and ensuring that the API meets the required specifications for crystalline form and purity.
• Quality Assurance (QA): Ensures that the XRD analysis is performed according to this SOP and reviews the results for regulatory compliance and product quality.
• Laboratory Personnel: Responsible for operating the XRD instrument, preparing samples, and maintaining the XRD equipment according to established guidelines.

4. Accountability

The QC Manager is accountable for ensuring the proper execution of the XRD analysis procedure, including sample preparation and result interpretation. The QA Manager is responsible for reviewing and approving the final results.

5. Procedure

5.1 Sample Preparation

1. Weigh a representative sample of the tablet (usually 1–2 g) from the batch for XRD analysis.
2. Ensure that the sample is free from contamination and physically homogeneous.
3. Crush the tablets into a fine powder to improve the resolution and accuracy of the XRD results. Use a mortar and pestle or mechanical grinder as appropriate.
4. Transfer the prepared powder into an appropriate sample holder, ensuring that the powder is evenly distributed and packed to avoid air gaps.

5.2 Instrument Calibration

1. Ensure that the X-ray diffraction (XRD) instrument is properly calibrated before use. Calibration should be performed using a standard reference material with known diffraction patterns.
2. Check the alignment of the XRD instrument, including the X-ray source, detector, and sample holder.
3. Verify that the instrument’s settings (e.g., scanning range, step size, scan speed) are correctly configured according to the SOP or test specifications.

5.3 Performing XRD Analysis

1. Place the sample holder with the prepared tablet powder into the XRD instrument’s sample chamber.
2. Set the desired scan parameters, such as the 2θ range (typically between 5° and 40°), scan speed (0.1°/min to 1°/min), and step size (0.01°–0.02°).
3. Start the analysis and allow the scan to complete. The instrument will generate a diffraction pattern corresponding to the crystallography of the API and excipients in the sample.

5.4 Data Interpretation

1. Review the resulting XRD diffraction pattern and compare it to reference patterns for the API to verify the crystalline form of the active ingredient.
2. Analyze the peaks, identifying the diffraction angles (2θ) and intensities. The presence of sharp, defined peaks typically indicates crystalline material, while broad peaks suggest amorphous forms.
3. If necessary, perform a quantitative analysis of the crystalline phases in the sample by comparing peak intensities to known standards or using quantitative XRD methods.
4. Document the XRD pattern and identify any deviations from the expected crystalline form, including the presence of polymorphic forms that may affect the drug’s stability or bioavailability.

5.5 Acceptance Criteria

1. Ensure that the diffraction pattern matches the expected pattern for the specified crystalline form of the API in the tablets. The pattern should show consistent peak positions and relative intensities as per the reference material.
2. If discrepancies are identified, investigate the cause and document findings in the deviation report (Annexure-1).
3. For regulatory compliance, the crystalline form should be confirmed as suitable for the intended therapeutic application and meet any specific regulatory requirements for polymorphic content.

5.6 Documentation and Record-Keeping

1. Record all XRD analysis results, including the diffraction patterns, data interpretation, and comparison with reference standards, in the batch record (Annexure-2).
2. Ensure that all records are signed, dated, and stored according to the company’s record retention policy for future audits and inspections.
3. Maintain raw data, including XRD spectra and calibration data, for regulatory compliance and reference purposes.

5.7 Post-Test Actions

1. Clean the XRD equipment and sample holder according to the cleaning SOP to avoid contamination between tests.
2. Ensure that any used materials or reagents are disposed of according to the company’s waste disposal procedures.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• API: Active Pharmaceutical Ingredient
• XRD: X-Ray Diffraction
• 2θ: Diffraction Angle

7. Documents

1. Batch Record (Annexure-2)
2. Deviation Report (Annexure-1)

8. References

• USP <811> – X-Ray Diffraction for Pharmaceutical Analysis
• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• European Pharmacopoeia (EP) – X-Ray Diffraction Specifications

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Deviation Report

Deviation Date	Batch Number	Deviation Description	Corrective Action	Responsible Person
15/12/2025	Batch 001	API polymorphic form identified	Reformulated to use stable polymorph	Jane Doe

Annexure-2: Batch Record

Batch Number	API Identified	2θ Angle	Peak Intensity	Result
Batch 001	API X	12.5°	2500 cps	Pass

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
01/01/2024	1.0	Initial Version	New SOP Creation	QA Head
01/02/2025	2.0	Updated Instrument Calibration Guidelines	Improved XRD method accuracy	QA Head