XRPDPolymorphQualityChecker

XRPD Polymorph Quality Checker — Polymorph Control (X-Ray Powder Diffraction)

ℹ️ Utility identifies polymorphic form and assesses crystallinity degree of active pharmaceutical ingredients by XRPD:
• Form Identification: Comparison of characteristic peak positions (2-Theta) with reference pattern
• Crystallinity Degree: Percentage of crystalline phase vs amorphous
• Peak Width (FWHM): Indicator of crystallite size and internal strain
• Detection of other polymorph impurities or amorphous phase

⚠️ CRITICAL: Presence of even trace amounts (1-2%) of metastable polymorph can lead to unpredictable changes in solubility, stability, and bioavailability!
Peak shift may indicate formation of solvates or solid solutions.

Usage:
XRPDPolymorphQualityChecker.exe → demo mode (console output)
XRPDPolymorphQualityChecker.exe input.csv output.json → evaluate your data

Input format:
BatchNumber,ProductName,IdentifiedForm,PeakPos1_2Theta,PeakPos2_2Theta,PeakPos3_2Theta,CrystallinityIndex,FWHM_Degrees

Example:
XRPD-2026-API-001,Ritonavir,Form I,12.5,18.2,24.1,98.5,0.15

— WHY IS THIS NEEDED?
Polymorphism is the ability of a substance to exist in different crystal structures.
Different polymorphs have different physicochemical properties (melting point, solubility, density).
For regulatory authorities (FDA, EMA), strict control of polymorphic form is a mandatory condition for drug registration.

⚠️ CRITICAL:
• Identification: At least 3-5 characteristic peaks must match within ±0.1-0.2° 2-Theta tolerance.
• Amorphous Phase: Appears as a "halo" on diffractogram and reduces peak intensity.
• Quantitative Analysis: Rietveld method or PLS regression is required for accurate determination of % impurity of another polymorph.
• Orientation: Preferred orientation effect can distort peak intensities but not their positions.

Key features:
• Polymorphic form identity check
• Crystal lattice quality control (FWHM)
• Overall crystallinity assessment
• Generation of reports for regulatory dossiers and LIMS LabWare
• Compliance with ICH Q6A and Pharmacopoeia requirements

Critical parameters:
• Peak Positions: Strict match with reference
• Identified Form: Strict compliance (e.g., Form I)
• Crystallinity: ≥ 95% (for highly crystalline forms)
• FWHM: ≤ 0.25° (depends on instrument and substance nature)

💡 Usage tips:
1. Sample Preparation: Avoid strong pressing of sample into holder, as it may cause polymorph transition or preferred orientation.
2. Calibration: Use external standard (e.g., silicon or corundum) for 2-Theta angle calibration.
3. Scan Speed: Slow scanning (e.g., 1-2°/min) improves peak resolution and signal-to-noise ratio.
4. Interpretation: If peaks match in position but differ in intensity, check for texture (orientation).
5. Storage: Some polymorphs are hygroscopic or unstable upon heating. Consider sample storage conditions.

⚠️ Note: XRPD is the "gold standard" for polymorph identification. Unlike DSC, it allows distinguishing forms with close melting points and quantitatively assessing amorphous phase.