Transmission powder X-ray diffraction technique for precise identification and quantification of drug polymorphs - a...

Area of Science:

• Solid-state chemistry
• Pharmaceutical analysis
• Crystallography

Background:

• Polymorphism in active pharmaceutical ingredients (APIs) significantly impacts drug efficacy and safety.
• Accurate identification and quantification of polymorphic forms are crucial for pharmaceutical development and quality control.
• Powder X-ray diffraction (PXRD) is a primary technique for characterizing solid-state forms.

Purpose of the Study:

• To compare the effectiveness of capillary transmission, foil transmission, and Bragg-Brentano reflection geometries in PXRD for phase identification and quantification.
• To evaluate these geometries using metformin embonate (ME) polymorphic forms as a model system.
• To determine the optimal PXRD geometry for accurate analysis of APIs.

Main Methods:

• PXRD analysis of metformin embonate (ME) forms I and II using three geometries: capillary transmission, foil transmission, and Bragg-Brentano reflection.
• Assessment of diffraction pattern quality, peak symmetry, and resolution.
• Rietveld refinement to evaluate data quality and perform quantitative analysis on polymorph mixtures.

Main Results:

• Foil and capillary transmission geometries produced symmetric, well-resolved diffraction peaks, superior to the broader, merged peaks from reflection geometry.
• Capillary transmission yielded the best profile fit (lowest Rwp and GOF), followed by foil transmission and then reflection.
• Foil transmission demonstrated excellent linearity for quantitative analysis of ME polymorph mixtures, outperforming reflection geometry, especially for heterogeneous samples with preferred orientation.

Conclusions:

• Foil transmission geometry offers a balanced approach, combining advantages of transmission and reflection methods while mitigating challenges like sample preparation and preferred orientation.
• This study establishes foil transmission as a highly effective method for polymorphic identification and quantification of APIs, surpassing traditional reflection methods in certain scenarios.
• The findings provide valuable insights for optimizing PXRD methods in the pharmaceutical industry for robust polymorph analysis.