Constant rate thermal analysis study of a trihydrate calcium atorvastatin and effect of grinding on its thermal stability

Abstract

The pathways of dehydration reaction of both calcium atorvastatin trihydrate (CAT) and grinded CAT were investigated using CRTA technique under controlled residual water vapor pressure of 5 hPa using complementary analysis techniques, namely TG, DSC and XRD. The results show that the studied sample is a pure atorvastatin in its trihydrated form and that, under CRTA conditions, it dehydrates in three separated steps between 261 and 393 K, each corresponds to the loss of one water molecule. On the other hand, the grinded CAT dehydrates in one step. From the duration of the CRTA experiment and the X-ray diffraction technique, we have showed that the grinding partially dehydrates CAT, to obtain calcium atorvastatin 1.5 H2O, while decreasing its crystallinity. Also, examination by X-ray diffraction technique of the CRTA final products of both, CAT and grinded CAT, showed that the anhydrous phase of CAT is crystallized, whereas the one of the grinded CAT is amorphous. The apparent activation energies corresponding to the dehydration steps of intact CAT (39 kJ mol-1 and 34 kJ mol-1) and grinded CAT (126 kJ mol-1 and 289 kJ mol-1) were obtained by means of two CRTA curves realized at two different reaction rates without any hypothesis on the kinetic model of the reaction.