Amorphous Enzalutamide – Non-isothermal recrystallization kinetics and thermal stability

Influence of particle size and manufacturing conditions on the recrystallization of amorphous Enzalutamide

“…The present study will continue the research presented in (Romanová et al, 2018), exploring the influence of different preparation routes (hot melt extrusion to different temperatures + spray drying) on the thermal stability and crystal growth processes in the amorphous Enzalutamide. The study aims to quantify the influence of particle size, storage temperature and storage conditions on the recrystallization kinetics.…”

“…As is well known, crystallization of organic glasses starts from surface (which is also true for Enzalutamide, as will be demonstrated later). In our preceding work on Enzalutamide (Romanová et al, 2018) it was shown that the presence of mechanically induced defects (Svoboda and Brandová, 2017;Brandová et al, 2018) plays major role in the crystallization process. In case of the lowest size (20 -50 µm) material, an excessive amount of mechanical defects and fractures apparently occurs on the surface of the particles.…”

“…2A and 2B (1 and 5 w.%). The mixtures were prepared from the original R1 crystalline Enzalutamide material (used for the preparation of the amorphous batches) and the fully amorphous material as prepared previously (Romanová et al, 2018). Whereas the LN 2 -cooled and spray-dried materials appear to be amorphous, the air-cooled batch of Enzalutamide seems to contain a low amount of crystals (well below 1 wt.%).…”

“…A considerable number of the recrystallization studies is nowadays being performed by using the non-isothermal differential scanning calorimetry (DSC). But only recently, see (Romanová et al, 2018), very few satisfactory predictions towards the below-T g crystal growth could be made based on the DSC data. It was shown in that paper (the study was performed for Enzalutamide) that by considering the temperature-based evolution of the above-T g non-isothermal recrystallization kinetics a correct prediction of the degree of amorphous-to-crystalline conversion can be made for the temperatures (storage) below the glass transition temperature.…”

Influence of DSC thermal lag on evaluation of crystallization kinetics

“…(dα•dt -1 increasing with ΔT pred due to the decreasing apparent E, which is a general consequence of larger temperature lags at higher q + ) but also the utmost importance of the predictions being made based on the correct set of the kinetic calculations. In case of the lowtemperature predictions the most relevant experimental measurements are those performed at low q + [30,31], which are often missing in literature; it is also important to bear in mind that E is by far the most crucial parameter in this regard, i.e. although the DSC data obtained at lower q + are usually of insufficient quality for high-r 2 description, they are still valuable for calculation of E.…”