Enhanced bioavailability of process-induced fast-dissolving @entity5018 cogranulated with XXXX .

@entity658 @entity11151 @entity5018 @entity12690 @entity6741 @entity19987 @entity35
The objectives of this study were to evaluate the bioavailability of cogranulated and oven-dried @entity5018 ( @entity12690 ) and @entity11151 ( @entity19987 ), in comparison to a physical mixture, and to examine the effect of endogenous bile on the bioavailability of the drug. In vitro dissolution studies were performed using USP type 2 apparatus. The granules and physical mixture were administered perorally in a crossover fashion, to male @entity35 bile duct-nonligated @entity35 . The granules were also perorally administered to bile duct-ligated @entity35 . Blood samples were taken at different time intervals and the plasma analyzed for @entity12690 . Dissolution of granules was faster than the physical mixture due to faster @entity12690 - @entity19987 complex formation in solution from the former than the latter. The in vivo study showed that C(max), AUC(0-8), and the absolute bioavailability for the granules (49.0 microg/mL, 57.0 h x microg/mL and 80.6%, respectively) were almost one and half times that of the physical mixture (32.2 microg/mL, 38.4 h x microg/mL and 53.1%, respectively). However, in bile duct-ligated @entity35 , lower C(max) and AUC(0-8) (15.9 microg/mL and 14.4 h x microg/mL, respectively) were obtained for the granules. Phase solubility study of @entity12690 in an aqueous @entity19987 solution in the presence of the @entity6741 ( @entity658 ), showed an increase in the solubility of @entity12690 . Moreover, the stability constant value for the @entity12690 - @entity19987 complex was also found to decrease as the @entity658 concentration increased. These results indicated that the enhancement in the bioavailability of @entity12690 was due to faster in-solution complex formation, and micelllar solubilization by the @entity6741 .
