Rietveld refinement in the routine quantitative analysis of famotidine polymorphs

Area of Science:

• Analytical Chemistry
• Materials Science
• Pharmaceutical Analysis

Background:

• Famotidine exists in multiple polymorphic forms, impacting drug efficacy and stability.
• Accurate quantification of these forms is crucial for pharmaceutical quality control.
• Existing methods like Raman spectroscopy have limitations in certain applications.

Purpose of the Study:

• To develop and validate a precise X-ray powder diffraction (XRPD) method for quantitative determination of famotidine polymorphic forms.
• To compare the performance of the developed XRPD method with the established Raman spectroscopy method.
• To optimize XRPD parameters for routine, high-throughput analysis.

Main Methods:

• Development of an X-ray powder diffraction method utilizing focused beam transmission geometry.
• Implementation of a straightforward transmission foil sample preparation technique.
• Application of Rietveld refinement for quantitative analysis of famotidine polymorphic forms in binary mixtures.

Main Results:

• The developed XRPD method demonstrated high accuracy, precision, and reliability for quantitative determination of famotidine polymorphic forms.
• The XRPD method slightly outperformed the previously established Raman method in terms of accuracy and reliability.
• Focused beam transmission geometry effectively minimized preferred orientation effects.
• Transmission foil sample preparation enabled efficient, high-throughput measurements.

Conclusions:

• The optimized XRPD method provides a robust and reliable approach for quantifying famotidine polymorphic forms.
• This method offers advantages over existing techniques, particularly in handling preferred orientation and enabling high-throughput analysis.
• The developed XRPD method is suitable for routine application in pharmaceutical quality control.