Enteric-coated tablets improve oral bioavailability of DX-9065, a novel anticoagulant

Oral bioavailability of DX-9065, a factor Xa inhibitor, was only 3% when it was administered as a conventional capsule formulation in fasted humans, and was further reduced to about one-tenth when it was administered to fed humans. The poor absorption of DX-9065 probably resulted from its low membrane permeability and its electrostatic interaction with bile acid. We designed enteric-coated tablets with the expectation that this pharmaceutical technology will prevent DX-9065 from interacting with bile acid. More than 85% of DX-9065 was released from the tablet coated with hypromellose acetate succinate within 10 min in simulated intestinal fluid (pH 6.8). Monkey experiments demonstrated that AUC of DX-9065 after oral administration of its enteric-coated tablet was about 5 times that of its aqueous solution in the fasted state. The food effect on drug absorption was also reduced when DX-9065 was administered as an enteric-coated tablet. The average ratio of AUC in a fed state to that in a fasted state was approximately 0.5, even though the ratio was 0.1 when the enteric-coated tablet was substituted with the drug solution. Enteric coating could be a useful method for improving oral absorption of DX-9065 with reduced food effects on drug absorption.

Graphical abstractOral absorption of DX-9065, which showed poor bioavailability due to its low membrane permeability and electrostatic interaction with bile acid, was improved by enteric-coated tablets.Figure optionsDownload full-size imageDownload as PowerPoint slide