Effect of Co‐Grinding on Crystallinity of Clopidogrel Bisulfate

Abstract

A high energy input during pharmaceutical formulation is capable of decreasing the crystallinity of compounds in the product. The presence of the amorphous form can cause serious problems at any stage of the formulation. Crystallinity changes of a model powder mixture containing clopidogrel bisulfate (CLP) and a colloidal silicon dioxide as additive were investigated during a long-time co-grinding process. The crystallinity of CLP was reduced sigmoidally by co-grinding with longer co-grinding time. X-ray powder diffraction and differential scanning calorimetry examinations confirmed that the product had become totally amorphous after four hours of grinding. Thermogravimetric results proved that no major mass reduction happened and FT-IR changes referred to formulation of a secondary bond between the components.

Monitoring the recrystallisation of amorphous xylitol using Raman spectroscopy and wide-angle X-ray scattering

“…Takeuchi et al (2005) also reported increased stability of solid dispersions containing amorphous indomethacin and silica particles. Mártha et al (2014) studied co-grinding of clopidogrel and silicon dioxide, and found that hydrogen bonding between silanol groups on the surface of silicon dioxide particles and the drug molecule resulted in a more stable amorphous structure. Hydrogen bonding similar to that between hydroxyl groups on the carrier surface and drug molecules could explain the decrease in crystallization rate in the bulk of the xylitol-silica dispersion in the present study, considering the molecular structure of xylitol (Watanabe et al, 2001;Takeuchi et al, 2005;Xu et al, 2013;Mártha et al, 2014).…”