XRD Phase Qualification and Quantification According to USP <941> and Ph. Eur.2.9.33
Quantification and qualification in X-ray diffraction (XRD) are key processes for ensuring the quality of pharmaceutical products, as outlined by USP <941>. Qualification involves identifying and confirming crystalline phases such as polymorphs in a sample by comparing the diffraction pattern with reference patterns. Quantification measures phase concentrations using a calibration curve developed from known concentrations and a standard. Both processes are critical for verifying polymorphs and concentration in pharmaceutical materials, ensuring regulatory compliance, and supporting product consistency and quality.
Introduction
Phase qualification and quantification are critical analytical processes used to determine the phases and the relative amounts of crystalline phases in a material. According to the United States Pharmacopeia (USP) <941> and Ph. Eur. 2.9.33, this ensures the quality, consistency, and efficacy of pharmaceutical substances by analyzing their solid-state properties. USP <941> and Ph.Eur.2.9.33 focus on the application of X‑ray powder diffraction (XRPD) as the primary technique for phase quantification. XRPD measures the diffraction pattern produced when a crystalline material is exposed to X-ray radiation, which is unique to specific phases of a substance. This method is particularly valuable for distinguishing between polymorphic forms, hydrates, solvates, and amorphous phases, all of which can significantly impact a drug's solubility, stability, and bioavailability.
The identification of the phase composition of an unknown sample using XRPD typically involves visual or computer-assisted comparison of a segment of its powder diffraction pattern with the experimental or calculated pattern of a reference material. Ideally, these reference patterns are obtained from well-characterized, single-phase specimens. This method enables the identification of a crystalline substance by analyzing its 2θ diffraction angles or d-spacings, along with their relative intensities. Typical 2θ deviations observed in this kind of investigations are around 0.2°. Quantitative phase analysis can be performed using integrated intensities, peak heights of multiple individual diffraction lines, or the full diffraction pattern. These values are then compared to the corresponding data from reference materials to determine phase composition (1,2)
References
- United States Pharmacopeia <941> Characterization of Crystalline and Partially Crystalline Solids by X-Ray Powder Diffraction (XRPD)
- European Pharmacopeia 2.9.33 Characterization of Crystalline and Partially Crystalline Solids by X-Ray Powder Diffraction (XRPD)
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