Effect of sample preparation method on quantification of polymorphs using PXRD

Abstract

The purpose of this study was to improve the sensitivity and accuracy of quantitative analysis of polymorphic mixtures. Various techniques such as hand grinding and mixing (in mortar and pestle), air jet milling and ball milling for micronization of particle and mixing were used to prepare binary mixtures. Using these techniques, mixtures of form I and form II of clopidogrel bisulphate were prepared in various proportions from 0–5% w/w of form I in form II and subjected to x-ray powder diffraction analysis. In order to obtain good resolution in minimum time, step time and step size were varied to optimize scan rate. Among the six combinations, step size of 0.05° with step time of 5 s demonstrated identification of maximum characteristic peaks of form I in form II. Data obtained from samples prepared using both grinding and mixing in ball mill showed good analytical sensitivity and accuracy compared to other methods. Powder x-ray diffraction method was reproducible, precise with LOD of 0.29% and LOQ of 0.91%. Validation results showed excellent correlation between actual and predicted concentration with R² > 0.9999.

Keywords::

• Clopidogrel bisulphate
• polymorphism
• preferred orientation
• quantitative analysis of polymorphs
• sample preparation method

Acknowledgements

Sarsvatkumar Patel would like to acknowledge DST, India for providing the young scientist award.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.