In vitro and in vivo evaluation of cyclodextrin-based nanosponges for enhancing oral bioavailability of atorvastatin calcium

The aim of this study was to explore the feasibility of complexing the poorly water-soluble drug atorvastatin calcium (AC) with β-cyclodextrin (β-CD) based nanosponges (NS), which offer advantages of improving dissolution rate and eventually oral bioavailability. Blank NS were fabricated at first by reacting β-CD with the cross-linker carbonyldiimidazole at different molar ratios (1:2, 1:4, and 1:8), then NS of highest solubilization extent for AC were complexed with AC. AC loaded NS (AC-NS) were characterized for various physicochemical properties. Pharmacokinetic, pharmacodynamics and histological finding of AC-NS were performed in rats. The prepared AC-NS showed particles size ranged from 408.7?±?12.9 to 423?±?15.9?nm while zeta potential values varied from ?21.7?±?0.90 to ?22.7?±?0.85?mV. The loading capacity varied from 17.9?±?1.21 to 34.1?±?1.16%. DSC, FT–IR, and PXRD studies confirmed the complexation of AC with NS and amorphous state of the drug in the complex. AC-NS displayed a biphasic release pattern with increase in the dissolution rate of AC as compared to plain AC. Oral administration of AC-NS (1:4 w/w, drug: NS) to rats led to 2.13-folds increase in the bioavailability as compared to AC suspension. Pharmacodynamics studies in rats with fatty liver revealed significant reduction (p?in vivo performance of AC.