A comparative study on in vitro and in vivo characteristics of enzalutamide nanocrystals versus amorphous solid dispersions and a better prediction for bioavailability based on 'spring-parachute' model

This study systematically compared enzalutamide (ENZ) nanocrystals and amorphous formulation (Xtandi® Tablets) and proposed an effective method for predicting pharmacokinetic behavior. ENZ nanosuspensions were prepared by anti-solvent precipitation (ENZ/NS-AS) and wet milling (ENZ/NS-WM) under optimal conditions and were solidified by spray drying and further tableting. Spray dried ENZ/NS-WM was confirmed to exist in crystalline state by DSC and PXRD, while spray dried ENZ/NS-AS was amorphous form. The dissolution testing revealed that ENZ/NS-WM tablets exhibited significantly faster dissolution rate than the physical mixture of untreated ENZ and HPMCAS-HG (1:1) prepared by gently grinding with a mortar and pestle for 2 min and were comparable to Xtandi® Tablets. However, the pharmacokinetic study in beagle dogs indicated that ENZ/NS-WM tablets displayed 0.43-fold lower C