용해도가 개선된 엔잘루타마이드 고체분산체 함유 정제의 개발

Abstract

The objective of this study was to develop a novel enzalutamide tablet formulation with enhanced solubilityand bioavailability, and inhibited recrystallization. Kollidon VA64 was selected as a soluble polymer for preparingenzalutamide solid dispersions. Solid dispersions with different enzalutamide to Kollidon VA64 weight ratios were preparedvia solvent evaporation method. The enzalutamide solid dispersion consisting of enzalutamide and Kollidon VA64 at aweight ratio of 1:1, exhibited an excellent dissolution rate and potent inhibition of recrystallization. Enzalutamide soliddispersions were characterized by scanning electron microscopy, powder X-ray diffractometry, differential scanningcalorimetry, and in vitro dissolution studies. The 1:1 solid dispersion exhibited excellent productivity, an elevateddissolution rate, and recrystallization inhibition. Therefore, enzalutamide solid dispersion loaded tablets were prepared andtheir dissolution was evaluated compared to a commercial product (Xtandi® soft capsule). The selected tablet formulationcontaining enzalutamide solid dispersion exhibited a higher dissolution rate in pH 1.0 solution than did the Xtandi® softcapsule, and prevented recrystallization of the enzalutamide. This research suggests that enzalutamide-containing soliddispersion tablets could be the most effective method to date for improving the dosing compliance of Xtandi® softcapsules, improving the dissolution rate of enzalutamide, and preventing recrystallization.