Enhanced Bioavailability of Process-Induced Fast-Dissolving Ibuprofen Cogranulated with β-Cyclodextrin

The objectives of this study were to evaluate the bioavailability of cogranulated and oven-dried ibuprofen (IBU) and β-cyclodextrin (βCD), 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 Wistar bile duct-nonligated rats. The granules were also perorally administered to bile duct-ligated rats. Blood samples were taken at different time intervals and the plasma analyzed for IBU. Dissolution of granules was faster than the physical mixture due to faster IBU–βCD complex formation in solution from the former than the latter. The in vivo study showed that Cmax, AUC0–8, and the absolute bioavailability for the granules (49.0 μg/mL, 57.0h·μg/mL and 80.6%, respectively) were almost one and half times that of the physical mixture (32.2 μg/mL, 38.4h·μg/mL and 53.1%, respectively). However, in bile duct-ligated rats, lower Cmax and AUC0–8 (15.9 μg/mL and 14.4h·μg/mL, respectively) were obtained for the granules. Phase solubility study of IBU in an aqueous βCD solution in the presence of the bile salt (sodium cholate), showed an increase in the solubility of IBU. Moreover, the stability constant value for the IBU–βCD complex was also found to decrease as the sodium cholate concentration increased. These results indicated that the enhancement in the bioavailability of IBU was due to faster in-solution complex formation, and micelllar solubilization by the bile salt. © 2003 Wiley-Liss, Inc. and the American Pharmacists Association