X-ray powder diffractometry in combination with principal component analysis – A tool for monitoring solid state changes

In this study a combined approach of analysing structural changes and elucidating the kinetics of the phase transformations by X-ray powder diffractometry (XRPD) and Raman spectroscopy with principal component analysis (PCA) during ball-milling was investigated. The effect of thermal and mechanical stress on three crystalline forms of piroxicam (PRX) was investigated with particular interest in preparation of amorphous form. Quench cooling of a melt, and ball-milling at room and low temperature were used for amorphisation. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were used for explaining the thermal behaviour of the samples. Partial amorphisation, the formation of anhydrous PRX form III (PRXAH III) and its transformation to anhydrous PRX form I (PRXAH I) were detected during ball-milling of anhydrous PRX forms at room temperature. However, ball-milling of PRX monohydrate (PRXMH) induced partial dehydration and amorphisation of the material. Ball-milling at low temperature produced amorphous PRX from PRXAH forms and only partially amorphous PRX from PRXMH, presumably due to the plasticising effect of the less bound water of crystallisation.

Graphical abstractBall-milling at low temperature was identified as the only suitable technique for preparing chemically pure amorphous piroxicam (PRX) from anhydrous PRX forms I and II. X-ray diffraction patterns and Raman spectra were subjected to principal component analysis (PCA) allowing efficient monitoring of phase transformations upon milling.Figure optionsDownload full-size imageDownload as PowerPoint slide